Translational Genomics: Practical Applications of the Genomic Revolution in Breast Cancer.

PubMed

Yates, Lucy R; Desmedt, Christine

2017-06-01

The genomic revolution has fundamentally changed our perception of breast cancer. It is now apparent from DNA-based massively parallel sequencing data that at the genomic level, every breast cancer is unique and shaped by the mutational processes to which it was exposed during its lifetime. More than 90 breast cancer driver genes have been identified as recurrently mutated, and many occur at low frequency across the breast cancer population. Certain cancer genes are associated with traditionally defined histologic subtypes, but genomic intertumoral heterogeneity exists even between cancers that appear the same under the microscope. Most breast cancers contain subclonal populations, many of which harbor driver alterations, and subclonal structure is typically remodeled over time, across metastasis and as a consequence of treatment interventions. Genomics is deepening our understanding of breast cancer biology, contributing to an accelerated phase of targeted drug development and providing insights into resistance mechanisms. Genomics is also providing tools necessary to deliver personalized cancer medicine, but a number of challenges must still be addressed. Clin Cancer Res; 23(11); 2630-9. ©2017 AACR See all articles in this CCR Focus section, "Breast Cancer Research: From Base Pairs to Populations." ©2017 American Association for Cancer Research.

Differences in Reliability of Reproductive History Recall among Women in North Africa

ERIC Educational Resources Information Center

Soliman, Amr; Allen, Katharine; Lo, An-Chi; Banerjee, Mousumi; Hablas, Ahmed; Benider, Abdellatif; Benchekroun, Nadya; Samir, Salwa; Omar, Hoda G.; Merajver, Sofia; Mullan, Patricia

2009-01-01

Breast cancer is the most common cancer among women in North Africa. Women in this region have unique reproductive profiles. It is essential to obtain reliable information on reproductive histories to help better understand the relationship between reductive health and breast cancer. We tested the reliability of a reproductive history-based…

Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease.

PubMed

Wardell, Suzanne E; Nelson, Erik R; Chao, Christina A; McDonnell, Donald P

2013-05-01

There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer. A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed. The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy. Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. ©2013 AACR.

A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

DTIC Science & Technology

2017-06-28

tracheostomy, radiation therapy, and hospice services. Introduction Breast cancer is the most commonly diagnosed cancer in women. The incidence of...evaluation, she acutely developed respiratory failure requiring emergent fiber-optic nasotracheal intubation and transfer to the medical intensive...17). OM and PM are thought to manifest as paraneoplastic syndromes when cancer cells overexpress myositis- specific antigens (MSA) that cause

Prostate-derived Ets factor, an oncogenic driver in breast cancer.

PubMed

Sood, Ashwani K; Geradts, Joseph; Young, Jessica

2017-05-01

Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed.

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

PubMed

Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

2015-08-01

Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Perspective from the Department of Defense Breast Cancer Research Program.

PubMed

Rich, I M; Andejeski, Y; Alciati, M H; Crawford Bisceglio, I; Breslau, E S; McCall, L; Valadez, A

1998-12-01

The Department of Defense (DOD), Breast Cancer Research Program (BCRP) was established in 1993. Since its inception, Congress has appropriated more than 878 million dollars for the BCRP, a unique public-private partnership between the DOD, consumer advocacy, and scientific communities which has funded approximately 1,800 breast cancer research grants. Through this partnership, the BCRP designed a model program for consumer involvement in scientific peer review. This paper describes the BCRP's approach to the processes of recruitment, selection, and preparation of consumers for this expanded role. Further, factors critical to program implementation, such as effective program management, ongoing process improvement, strong program leadership, and allocation of resources, that led to the BCRP's success in developing the previously undefined role of breast cancer survivors as members of scientific peer review panels are discussed. The BCRP demonstrates the feasibility and unique contributions of consumers in scientific peer review and provides a critical foundation for future efforts to ensure consumer involvement in scientific research programs.

Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer.

PubMed

Anbalagan, Muralidharan; Rowan, Brian G

2015-12-15

Estrogen receptor α (ERα) is a member of the nuclear receptor superfamily of transcription factors that regulates cell proliferation, differentiation and homeostasis in various tissues. Sustained exposure to estrogen/estradiol (E2) increases the risk of breast, endometrial and ovarian cancers. ERα function is also regulated by phosphorylation through various kinase signaling pathways that will impact various ERα functions including chromatin interaction, coregulator recruitment and gene expression, as well impact breast tumor growth/morphology and breast cancer patient response to endocrine therapy. However, many of the previously characterized ERα phosphorylation sites do not fully explain the impact of receptor phosphorylation on ERα function. This review discusses work from our laboratory toward understanding a role of ERα site-specific phosphorylation in ERα function and breast cancer. The key findings discussed in this review are: (1) the effect of site specific ERα phosphorylation on temporal recruitment of ERα and unique coactivator complexes to specific genes; (2) the impact of stable disruption of ERα S118 and S167 phosphorylation in breast cancer cells on eliciting unique gene expression profiles that culminate in significant effects on breast cancer growth/morphology/migration/invasion; (3) the Src kinase signaling pathway that impacts ERα phosphorylation to alter ERα function; and (4) circadian disruption by light exposure at night leading to elevated ERK1/2 and Src kinase and phosphorylation of ERα, concomitant with tamoxifen resistance in breast tumor models. Results from these studies demonstrate that even changes to single ERα phosphorylation sites can have a profound impact on ERα function in breast cancer. Future work will extend beyond single site phosphorylation analysis toward identification of specific patterns/profiles of ERα phosphorylation under different physiological/pharmacological conditions to understand how common phosphorylation profiles in breast cancer program specific physiological endpoints such as growth, apoptosis, migration/invasion, and endocrine therapy response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Psychosocial issues experienced by young women with breast cancer: the minority group with the majority of need.

PubMed

Ahmad, Saunia; Fergus, Karen; McCarthy, Molly

2015-09-01

The ways in which biological, social, and psychological factors characteristically unfold and interact for young women with breast cancer yields complex and acute challenges that are not clearly understood by all healthcare professionals. Better knowledge of the unique needs of young women with breast cancer would assist in matching younger women with the right services at the right time. Younger women (<50 years) represent a minority of breast cancer cases, yet they tend to be overrepresented with respect to demonstrating the poorest psychosocial adjustment during and following treatment. Concerns most frequently reported in this age group pertained to body image, sexual functioning, fertility, relationships, fear of cancer recurrence, and caring for children; failure of healthcare providers to initiate conversations to educate women about treatment side effects early on and/or safely discuss sensitive issues; lack of widespread availability of professional psychosocial programs that are tailored to the unique needs of this age group. Young women with breast cancer are at greater risk for psychosocial adjustment problems, yet their needs are often overlooked. Proactive discussions by healthcare providers early on in treatment, and referrals to relevant services as part of standard care are needed to mitigate younger women's concerns and reduce the likelihood of problems becoming longstanding.

Metabolic profiles are principally different between cancers of the liver, pancreas and breast.

PubMed

Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng; Hussain, S Perwez; Ambs, Stefan; Wang, Xin Wei

2014-01-01

Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin.

Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

PubMed

Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

2009-01-01

Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

Breast Cancer Diagnosis Using Ultrasound and Diffusive Light

DTIC Science & Technology

2004-08-01

been widely used in clinical studies. The fundamental problem remains the intense light scattering in tissue, which makes the lesion localization...Our 3 unique approach may have significant clinical applications on 1) breast cancer diagnosis; and 2) assessing treatment response and estimating...the response of cancers to presurgical chemotherapy are not completely understood [20]. Although recent trials reported clinical response rates >70

Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Min; Li, Ruishu, E-mail: liruishu2016@yahoo.com; Zhang, Juan

Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptoticmore » effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.« less

Frequencies of Private Mentions and Sharing of Mammography and Breast Cancer Terms on Facebook: A Pilot Study.

PubMed

Huesch, Marco; Chetlen, Alison; Segel, Joel; Schetter, Susann

2017-06-09

The most popular social networking site in the United States is Facebook, an online forum where circles of friends create, share, and interact with each other's content in a nonpublic way. Our objectives were to understand (1) the most commonly used terms and phrases relating to breast cancer screening, (2) the most commonly shared website links that other women interacted with, and (3) the most commonly shared website links, by age groups. We used a novel proprietary tool from Facebook to analyze all of the more than 1.7 million unique interactions (comments on stories, reshares, and emoji reactions) and stories associated with breast cancer screening keywords that were generated by more than 1.1 million unique female Facebook users over the 1 month between November 15 and December 15, 2016. We report frequency distributions of the most popular shared Web content by age group and keywords. On average, each of 59,000 unique stories during the month was reshared 1.5 times, commented on nearly 8 times, and reacted to more than 20 times by other users. Posted stories were most often authored by women aged 45-54 years. Users shared, reshared, commented on, and reacted to website links predominantly to e-commerce sites (12,200/1.7 million, 36% of all the most popular links), celebrity news (n=8800, 26%), and major advocacy organizations (n=4900, 15%; almost all accounted for by the American Cancer Society breast cancer site). On Facebook, women shared and reacted to links to commercial and informative websites regarding breast cancer and screening. This information could inform patient outreach regarding breast cancer screening, indirectly through better understanding of key issues, and directly through understanding avenues for paid messaging to women authoring and reacting to content in this space. ©Marco Huesch, Alison Chetlen, Joel Segel, Susann Schetter. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.06.2017.

Frequencies of Private Mentions and Sharing of Mammography and Breast Cancer Terms on Facebook: A Pilot Study

PubMed Central

Chetlen, Alison; Segel, Joel; Schetter, Susann

2017-01-01

Background The most popular social networking site in the United States is Facebook, an online forum where circles of friends create, share, and interact with each other’s content in a nonpublic way. Objective Our objectives were to understand (1) the most commonly used terms and phrases relating to breast cancer screening, (2) the most commonly shared website links that other women interacted with, and (3) the most commonly shared website links, by age groups. Methods We used a novel proprietary tool from Facebook to analyze all of the more than 1.7 million unique interactions (comments on stories, reshares, and emoji reactions) and stories associated with breast cancer screening keywords that were generated by more than 1.1 million unique female Facebook users over the 1 month between November 15 and December 15, 2016. We report frequency distributions of the most popular shared Web content by age group and keywords. Results On average, each of 59,000 unique stories during the month was reshared 1.5 times, commented on nearly 8 times, and reacted to more than 20 times by other users. Posted stories were most often authored by women aged 45-54 years. Users shared, reshared, commented on, and reacted to website links predominantly to e-commerce sites (12,200/1.7 million, 36% of all the most popular links), celebrity news (n=8800, 26%), and major advocacy organizations (n=4900, 15%; almost all accounted for by the American Cancer Society breast cancer site). Conclusions On Facebook, women shared and reacted to links to commercial and informative websites regarding breast cancer and screening. This information could inform patient outreach regarding breast cancer screening, indirectly through better understanding of key issues, and directly through understanding avenues for paid messaging to women authoring and reacting to content in this space. PMID:28600279

GPER-1/GPR30 a novel estrogen receptor sited in the cell membrane: therapeutic coupling to breast cancer.

PubMed

Molina, Luis; Figueroa, Carlos D; Bhoola, Kanti D; Ehrenfeld, Pamela

2017-08-01

Breast cancer is clinically classified as 'estrogen-positive' when at least 1% of cancer cells stain for the estrogen receptor alpha (ERα). However, recent research on both basic and clinical aspects of breast cancer suggests that GPER-1 (G protein-coupled estrogen receptor-1) may have an important role in breast cancer. Areas covered: This review provides a comprehensive and systematic literature search on GPER-1. We have focused on the role of GPER-1 in breast cancer and on resistance to endocrine therapy, an unsolved clinical issue still under discussion. Expert opinion: The discovery of GPER-1 as a novel estrogen receptor is unique and the signaling pathways activated by its stimulation, when compared to the classical nuclear ERα, indicate a potential role of GPER-1 in the genesis and mechanisms of drug resistance in breast cancer. Tumors expressing ERα represent the largest group of breast cancer patients indicating that more women eventually die from ERα-positive breast tumors than from other more malignant breast cancer subtypes such as HER2-positive and the triple negative groups. It is important to develop new strategies on endocrine therapy with regard to ERα and GPER-1 receptors to achieve innovative successful therapeutic tools.

Impact of Soy Foods on the Development of Breast Cancer and the Prognosis of Breast Cancer Patients.

PubMed

Messina, Mark

2016-01-01

The relationship between soy food intake and breast cancer has been rigorously investigated for more than 25 years. The identification of isoflavones as possible chemopreventive agents helped fuel this line of investigation. These diphenolic compounds, which are found in uniquely-rich amounts in soy beans, possess both estrogen-dependent and -independent properties that potentially inhibit the development of breast cancer. Observational studies show that among Asian women higher soy consumption is associated with an approximate 30% reduction in risk of developing breast cancer. However, evidence suggests that for soy to reduce breast cancer risk consumption must occur early in life, that is during childhood and/or adolescence. Despite the interest in the role of soy in reducing breast cancer risk concerns have arisen that soy foods, because they contain isoflavones, may increase the likelihood of high-risk women developing breast cancer and worsen the prognosis of breast cancer patients. However, extensive clinical and epidemiologic data show these concerns to be unfounded. Clinical trials consistently show that isoflavone intake does not adversely affect markers of breast cancer risk, including mammographic density and cell proliferation. Furthermore, prospective epidemiologic studies involving over 11,000 women from the USA and China show that postdiagnosis soy intake statistically significantly reduces recurrence and improves survival. © 2016 S. Karger GmbH, Freiburg.

A community intervention: AMBER: Arab American breast cancer education and referral program.

PubMed

Ayash, Claudia; Axelrod, Deborah; Nejmeh-Khoury, Sana; Aziz, Arwa; Yusr, Afrah; Gany, Francesca M

2011-12-01

Although the number of Arab Americans is growing in the United States, there is very little data available on this population's cancer incidence and screening practices. Moreover, there are few interventions addressing their unique needs. This study aims to determine effective strategies for increasing breast cancer screening in at-risk underserved Arab American women. AMBER utilizes a community based participatory approach to conduct formative research and program interventions, including culturally appropriate Arabic language breast cancer education, screening coordination, and cultural competency training for healthcare professionals in New York City. In 2 years, 597 women were educated, 189 underserved women were identified as being in need of assistance, 68 were screened, one new case of breast cancer was detected, and four active cases in need of follow-up reconnected with care. The AMBER model is an important intervention for breast cancer screening and care in the underserved Arab American community.

Breast Cancer Translational Research Center of Excellence

DTIC Science & Technology

2015-09-01

we will identify partner proteins by either Y2H or pull-down studies using Mass Spectrometry Analysis. Aim 2. Development of DNA aptamers against...CD44 that inhibit breast cancer invasion and metastasis. During the previous period, we developed novel and unique DNA aptamers that specifically...bound to exon v10 of CD44 using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) systems. These DNA aptamers inhibited TN breast

Metastatic breast cancer to the rectum: A case report with emphasis on MRI features.

PubMed

Lau, Li Ching; Wee, Bernard; Wang, Shi; Thian, Yee Liang

2017-04-01

Less than 1% of breast carcinomas metastasize to the gastrointestinal tract. The diagnosis is frequently not recognized especially when the history of breast carcinoma is remote. A 61-year-old female with a remote history of breast carcinoma presented with a 3-month history of change in bowel habits. Colonoscopy showed a circumferential rectal mass with initial impression of primary rectal cancer. MRI of the rectum showed findings that are atypical for primary rectal cancer. Deep biopsy of the rectal mass confirmed lobular breast carcinoma metastasis to the rectum. The patient was treated with radiotherapy and hormonal therapy. She is symptomatically well 2 years after presentation and remains on hormonal therapy. Lobular breast cancer which metastasizes to the rectum can mimic primary rectal cancer clinically. The unique MRI features described in our case when present with a concordant history of lobular breast carcinoma should alert the radiologist to the possibility of this diagnosis which has important treatment implications.

Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention

PubMed Central

Martinson, Holly A.; Lyons, Traci R.; Giles, Erin D.; Borges, Virginia F.; Schedin, Pepper

2014-01-01

The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. PMID:23664839

Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer.

PubMed

Baker, Julie A; Beehler, Gregory P; Sawant, Abhishek C; Jayaprakash, Vijayvel; McCann, Susan E; Moysich, Kirsten B

2006-01-01

Caffeine has been suggested as a possible risk factor for breast cancer, potentially through its effect of facilitating the development of benign breast disease. However, coffee and tea also contain polyphenols, which exhibit anticarcinogenic properties. A hospital-based, case-control study was conducted to evaluate the role of coffee, decaffeinated coffee, and black tea in breast cancer etiology. Study participants included 1932 cases with primary, incident breast cancer and 1895 hospital controls with nonneoplastic conditions. All participants completed a comprehensive epidemiological questionnaire. Among premenopausal women, consumption of regular coffee was associated with linear declines in breast cancer risk (P for trend = 0.03); consumers of >or=4 cups/d experienced a 40% risk reduction (odds ratio = 0.62, 95% CI 0.39-0.98). No clear associations between intake of black tea or decaffeinated coffee and breast cancer risk were noted among premenopausal women, although black tea was associated with a protective effect unique to a subsample of cases with lobular histology. Among postmenopausal women, breast cancer risk was not associated with consumption of coffee, tea, or decaffeinated coffee. Results among postmenopausal women did not differ by histologic subtype. Our findings support a protective effect of coffee intake on premenopausal, but not postmenopausal breast cancer risk. Further studies are warranted to confirm these findings.

Herceptin Enhances the Antitumor Effect of Natural Killer Cells on Breast Cancer Cells Expressing Human Epidermal Growth Factor Receptor-2.

PubMed

Tian, Xiao; Wei, Feng; Wang, Limei; Yu, Wenwen; Zhang, Naining; Zhang, Xinwei; Han, Ying; Yu, Jinpu; Ren, Xiubao

2017-01-01

Optimal adoptive cell therapy (ACT) should contribute to effective cancer treatment. The unique ability of natural killer (NK) cells to kill cancer cells independent of major histocompatibility requirement makes them suitable as ACT tools. Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2) monoclonal antibody, is used to treat HER2 + breast cancer. However, it has limited effectiveness and possible severe cardiotoxicity. Given that Herceptin may increase the cytotoxicity of lymphocytes, we explored the possible augmentation of NK cell cytotoxicity against HER2 + breast cancer cells by Herceptin. We demonstrated that Herceptin could interact with CD16 on NK cells to expand the cytotoxic NK (specifically, CD56 dim ) cell population. Additionally, Herceptin increased NK cell migration and cytotoxicity against HER2 + breast cancer cells. In a pilot study, Herceptin-treated NK cells shrunk lung nodular metastasis in a woman with HER2 + breast cancer who could not tolerate the cardiotoxic side effects of Herceptin. Our findings support the therapeutic potential of Herceptin-treated NK cells in patients with HER2 + and Herceptin-intolerant breast cancer.

Anti-epidermal growth factor receptor (anti-EGFR) antibody conjugated fluorescent nanoparticles probe for breast cancer imaging

NASA Astrophysics Data System (ADS)

Hun, Xu; Zhang, Zhujun

2009-10-01

Fluorescent nanoparticles (FNs) with unique optical properties may be useful as biosensors in living cancer cell imaging and cancer targeting. In this study, anti-EGFR antibody conjugated fluorescent nanoparticles (FNs) (anti-EGFR antibody conjugated FNs) probe was used to detect breast cancer cells. FNs with excellent character such as non-toxicity and photostability were first synthesized with a simple, cost-effective and environmentally friendly modified Stőber synthesis method, and then successfully modified with anti-EGFR antibody. This kind of fluorescence probe based on the anti-EGFR antibody conjugated FNs has been used to detect breast cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the anti-EGFR antibody conjugated FNs can effectively recognize breast cancer cells and exhibited good sensitivity and exceptional photostability, which would provide a novel way for the diagnosis and curative effect observation of breast cancer cells and offer a new method in detecting EGFR.

Breast Cancer: A Molecular and Redox Snapshot.

PubMed

Raman, Deepika; Foo, Chuan Han Jonathan; Clement, Marie-Veronique; Pervaiz, Shazib

2016-08-20

Breast cancer is a unique disease characterized by heterogeneous cell populations causing roadblocks in therapeutic medicine, owing to its complex etiology and primeval understanding of the biology behind its genesis, progression, and sustenance. Globocan statistics indicate over 1.7 million new breast cancer diagnoses in 2012, accounting for 25% of all cancer morbidities. Despite these dismal statistics, the introduction of molecular gene signature platforms, progressive therapeutic approaches in diagnosis, and management of breast cancer has led to more effective treatment strategies and control measures concurrent with an equally reassuring decline in the mortality rate. However, an enormous body of research in this area is requisite as high mortality associated with metastatic and/or drug refractory tumors continues to present a therapeutic challenge. Despite advances in systemic chemotherapy, the median survival of patients harboring metastatic breast cancers continues to be below 2 years. Hence, a massive effort to scrutinize and evaluate chemotherapeutics on the basis of the molecular classification of these cancers is undertaken with the objective to devise more attractive and feasible approaches to treat breast cancers and improve patients' quality of life. This review aims to summarize the current understanding of the biology of breast cancer as well as challenges faced in combating breast cancer, with special emphasis on the current battery of treatment strategies. We will also try and gain perspective from recent encounters on novel findings responsible for the progression and metastatic transformation of breast cancer cells in an endeavor to develop more targeted treatment options. Antioxid. Redox Signal. 25, 337-370.

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations.

PubMed

Gómez-Flores-Ramos, Liliana; Castro-Sánchez, Andrea; Peña-Curiel, Omar; Mohar-Betancourt, Alejandro

2017-01-01

Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

Application of Raman Spectroscopy and Infrared Spectroscopy in the Identification of Breast Cancer.

PubMed

Depciuch, Joanna; Kaznowska, Ewa; Zawlik, Izabela; Wojnarowska, Renata; Cholewa, Marian; Heraud, Philip; Cebulski, Józef

2016-02-01

Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact verifies that Raman spectroscopy and IR spectroscopy are very useful diagnostic tools that will shed new light in understanding the etiology of breast cancer. © The Author(s) 2016.

The Sister Study Cohort: Baseline Methods and Participant Characteristics

PubMed Central

Hodgson, M. Elizabeth; Deming-Halverson, Sandra L.; Juras, Paula S.; D’Aloisio, Aimee A.; Suarez, Lourdes M.; Kleeberger, Cynthia A.; Shore, David L.; DeRoo, Lisa A.; Taylor, Jack A.; Weinberg, Clarice R.

2017-01-01

Background: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. Objective: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. Methods: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. Results: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35–74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment. Conclusions: The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923 PMID:29373861

Breast cancer survivorship and South Asian women: understanding about the follow-up care plan and perspectives and preferences for information post treatment

PubMed Central

Singh–Carlson, S.; Wong, F.; Martin, L.; Nguyen, S.K.A.

2013-01-01

Background and Objectives As more treatment options become available and supportive care improves, a larger number of people will survive after treatment for breast cancer. In the present study, we explored the experiences and concerns of female South Asian (sa) breast cancer survivors (bcss) from various age groups after treatment to determine their understanding of follow-up care and to better understand their preferences for a survivorship care plan (scp). Methods Patients were identified by name recognition from BC Cancer Agency records for sa patients who were 3–60 months post treatment, had no evidence of recurrence, and had been discharged from the cancer centre to follow-up. Three focus groups and eleven face-to-face semistructured interviews were audio-recorded, transcribed verbatim, cross-checked for accuracy, and analyzed using thematic and content analysis. Participants were asked about their survivorship experiences and their preferences for the content and format of a scp. Results Fatigue, cognitive changes, fear of recurrence, and depression were the most universal effects after treatment. “Quiet acceptance” was the major theme unique to sa women, with a unique cross-influence between faith and acceptance. Emphasis on a generalized scp with individualized content echoed the wide variation in breast cancer impacts for sa women. Younger women preferred information on depression and peer support. Conclusions For sa bcss, many of the psychological and physical impacts of breast cancer diagnosis and treatment may be experienced in common with bcss of other ethnic backgrounds, but the present study also suggests the presence of unique cultural nuances such as spiritual and language-specific support resource needs. The results provide direction for designing key content and format of scps, and information about elements of care that can be customized to individual patient needs. PMID:23559888

Skin thickening as unique pathologic sign of an inflammatory breast cancer: a case report and review of the literature.

PubMed

Ballesio, L; D'Ambrosio, I; Ravazzolo, N; Angeletti, M; Di Pastena, F; Tardioli, S; Lodise, P; Marini, M

2011-01-01

We report the case of a 42-year-old woman with inflammatory cancer of the right breast treated with neoadjuvant chemotherapy, surgery, additional chemotherapy, and consolidative radiotherapy (RT), that has metastatized to the chest wall and presented a resumption of disease on the contralateral breast. Magnetic Resonance (MR), performed after the second phase's fourth round of additional chemotherapy, showed a modest reduction of scar metastases on the right and a contralateral anomalous skin thickening with high signal intensity in T2 weighted images (WI) with multiple mass-like enhancements located in a wide area of the central region at the union of higher quadrants. These findings were suggestive for resumption of contralateral disease; the biopsy confirmed an inflammatory breast cancer (IBC) infiltrating lobular type with high mitotic rate. A retrospective evaluation of the previous MR exam, performed 5 months before, was conducted: on the left side only a modest skin thickening was found as an early sign. A careful review of the literature has confirmed that skin thickening, increased density and clinical signs of inflammation are the most common findings in inflammatory cancer. We report the case of a patient affected by IBC whose unique early sign of resumption on the contralateral breast was skin thickening.

Long wavelength identification of microcalcifications in breast cancer tissue using a quantum cascade laser and upconversion detection

NASA Astrophysics Data System (ADS)

Tseng, Y. P.; Bouzy, P.; Stone, N.; Pedersen, C.; Tidemand-Lichtenberg, P.

2018-02-01

Spectral imaging in the long-wave infrared regime has great potential for medical diagnostics. Breast cancer is the most common cancer amongst females in the US. The pathological features and the occurrence of the microcalcifications are still poorly understood. However, two types of microcalcifications have been identified as unique biomarkers: type I consisting of calcium oxalate (benign lesions) and type II composed of hydroxyapatite (benign or invasive lesions). In this study, we propose a new approach based on vibrational spectroscopy that is non-destructive, label-free and chemically specific for breast cancer detection. Long-wave infrared spectroscopy combining quantum cascade lasers (QCL) and upconversion detection, offer to improve signal-to-noise ratios compared to standard long-wave infrared spectroscopy. We demonstrated long-wave identification of synthetic samples of carbonated hydroxyapatite and of microcalcification in breast cancer tissue using upconversion detection. Absorbance spectra and upconverted images of in situ breast cancer biopsy are compared with that of Fourier-transform infrared (FTIR) spectroscopy.

Evolving psychosocial, emotional, functional, and support needs of women with advanced breast cancer: Results from the Count Us, Know Us, Join Us and Here & Now surveys.

PubMed

Cardoso, Fatima; Harbeck, Nadia; Mertz, Shirley; Fenech, Doris

2016-08-01

Although medical advances have marginally improved survival of women with advanced breast cancer, their psychosocial, emotional, and functional needs remain unmet. Two surveys, Count Us, Know Us, Join Us (Count Us) and Here & Now (H&N), were conducted to understand the unique challenges faced by women with advanced breast cancer and to identify ways of addressing these issues. A total of 1577 women with advanced breast cancer (Count Us, N = 1273; H&N, N = 304) participated in the two surveys, which revealed several previously unreported challenges. Nearly half the women felt isolated and worried, and slightly more than half experienced declines in income because of change in employment; 41% of women felt that support from family and friends decreased over time, and many patients believed information about advanced breast cancer was inadequate and difficult to find. Concerted efforts by people who care for and support women with advanced breast cancer are urgently needed to address these issues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study of anti-cancer effects of chemotherapeutic agents and radiotherapy in breast cancer patients using fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Chithra, K.; Vijayaraghavan, S.; Prakasarao, Aruna; Singaravelu, Ganesan

2017-02-01

The analysis of the variations in the spectroscopic patterns of the key bio molecules using Native fluorescence spectroscopy, without exogenous labels, has emerged as a new trend in the characterization of the Physiological State and the Discrimination of Pathological from normal conditions of cells and tissues as the relative concentration of these bio-molecules serve as markers in evaluating the presence of cancer in the body. The aim of this unique study is to use these features of Optical spectroscopy in monitoring the behavior of cells to treatment and thus to evaluate the response to Chemotherapeutic agents and Radiation in Breast Cancer Patients. The results of the study conducted using NFS of Human blood plasma of biopsy proved Breast Cancer patients undergoing treatment are promising, enhancing the scope of Native fluorescence Spectroscopy emerging as a promising technology in the evaluation of Therapeutic Response in Breast Cancer Patients.

Detection of cystic structures using pulsed ultrasonically induced resonant cavitation

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph (Inventor); Kovach, John S. (Inventor)

2002-01-01

Apparatus and method for early detection of cystic structures indicative of ovarian and breast cancers uses ultrasonic wave energy at a unique resonance frequency for inducing cavitation in cystic fluid characteristic of cystic structures in the ovaries associated with ovarian cancer, and in cystic structures in the breast associated with breast cancer. Induced cavitation bubbles in the cystic fluid implode, creating implosion waves which are detected by ultrasonic receiving transducers attached to the abdomen of the patient. Triangulation of the ultrasonic receiving transducers enables the received signals to be processed and analyzed to identify the location and structure of the cyst.

Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

PubMed Central

Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

2014-01-01

Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

Productivity Costs Associated With Breast Cancer Among Survivors Aged 18-44 Years.

PubMed

Ekwueme, Donatus U; Trogdon, Justin G; Khavjou, Olga A; Guy, Gery P

2016-02-01

No study has quantified productivity losses associated with breast cancer in younger women aged 18-44 years. This study estimated productivity costs, including work and home productivity losses, among younger women who reported ever receiving a breast cancer diagnosis. A two-part regression model and 2000-2010 National Health Interview Survey data were used to estimate the number of work and home productivity days missed because of breast cancer, adjusted for socioeconomic characteristics and comorbidities. Estimates for younger women were compared with those for women aged 45-64 years. Data were analyzed in 2013-2014. Per capita, younger women with breast cancer had annual losses of $2,293 (95% CI=$1,069, $3,518) from missed work and $442 (95% CI=$161, $723) from missed home productivity. Total annual breast cancer-associated productivity costs for younger women were $344 million (95% CI=$154 million, $535 million). Older women with breast cancer had lower per capita work loss productivity costs of $1,407 (95% CI=$899, $1,915) but higher total work loss productivity costs estimated at $1,072 million (95% CI=$685 million, $1,460 million) than younger women. Younger women with a history of breast cancer face a disproportionate share of work and home productivity losses. Although older women have lower per capita costs, total productivity costs were higher for older women because the number of older women with breast cancer is higher. The results underscore the importance of continued efforts by the public health community to promote and support the unique needs of younger breast cancer survivors. Published by Elsevier Inc.

The impact of culture and sociological and psychological issues on Muslim patients with breast cancer in Pakistan.

PubMed

Banning, Maggi; Hafeez, Haroon; Faisal, Saima; Hassan, Mariam; Zafar, Ammarah

2009-01-01

Breast cancer is the most common form of cancer in Muslim women in Pakistan. The impact of the initial diagnosis, culture, religion, and psychosocial and psychological aspects of the disease is not well established. This qualitative study examined the experience and coping strategies used by patients with breast cancer in relation to its impact on their physical, mental health, religious, and family issues. Thirty patients with breast cancer were interviewed. Data were analyzed using thematic analysis. The patient's experience of breast cancer focused on the range of emotions felt throughout the illness trajectory, the importance of religion and family support on coping strategies used to manage the adverse effects of chemotherapy, and also the financial concerns. This is the first study to examine Pakistani Muslim women's views on the lived experience of breast cancer. This article provides clarification of the voiced experiences of women with breast cancer. The data not only highlight the role of religion and family support as essential coping strategies but also emphasize the issues of isolation, aggression, and anger as common responses to chemotherapy. Unique features of this study are women's need to seek spiritual support for their illness and the overriding innate characteristic of maternal responsibility. These cultural features require further analysis and research.

The Department of Defense Congressionally Directed Medical Research Program: innovations in the federal funding of biomedical research.

PubMed

Young-McCaughan, Stacey; Rich, Irene M; Lindsay, Gaylord C; Bertram, Kenneth A

2002-04-01

In response to the lobbying efforts of the women's advocacy movement, in 1993 Congress authorized funds for a substantial increase in support of new and promising research aimed at the eradication of breast cancer. This appropriation resulted in a major expansion of the United States Army Medical Research and Materiel Command, Department of Defense Breast Cancer Research Program. The Office of Congressionally Directed Medical Research Programs was established within the United States Army Medical Research and Materiel Command to facilitate the management of the expanded extramural research program. Since that time, the programs have grown to include not just breast cancer but also prostate cancer, ovarian cancer, and neurofibromatosis. The unique appropriations to the Office of Congressionally Directed Medical Research Programs has resulted in a number of programmatic innovations. These include development of unique mechanisms of grant support, inclusion of consumer advocates on peer and programmatic review panels, and the introduction of criteria-based evaluation and scoring in peer review. This article describes these novel scientific management strategies and outlines their success in meeting program visions and goals.

Isolation and prayer as means of solace for Arab women with breast cancer: An in-depth interview study.

PubMed

Assaf, Ghada Najjar; Holroyd, Eleanor; Lopez, Violeta

2017-11-01

This study explored Arab women's experiences following the diagnosis and treatment of breast cancer. Face-to-face in-depth interviews were conducted with 20 Arab women attending a public hospital in Abu Dhabi, United Arab Emirates, following a recent diagnosis of breast cancer. All interviews were transcribed verbatim and analysed using the thematic method. Arab women's experiences following their breast cancer diagnoses and treatments included the themes of (1) protecting one's self from stigma, (2) facing uncertainties and prayers, and (3) getting on with life. Overall, the ways to find solace were through isolation and prayer, which are heavily influenced by religion and spiritual practices. They recommended that to help women with breast cancer, a campaign to raise awareness for early screening is needed as well the need to form a peer-led support group for women with breast cancer consisting of breast cancer survivors so that they can learn from each other's experiences. Arab women with breast cancer experienced a myriad of social, cultural, psychological, and relationship difficulties that impacted their overall health and well-being. The findings also found that these women were not passive agents. They sought to solve problem, move forward, and recreate the meanings in their lives in their own unique ways. Action is needed for possible ways to implement religion-health partnerships between breast cancer nurses, peer-led support groups, palliative care services, and religious institutions. Copyright © 2017 John Wiley & Sons, Ltd.

Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis.

PubMed

Peng, Wenjing; Zhang, Yu; Zhu, Rui; Mechref, Yehia

2017-09-01

Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label-free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label-free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up-regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down-regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up-regulation of integrin proteins and down-regulation of EPHA2 in brain metastasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

PubMed Central

Wong, Ada Hang-Heng; Vazquez-Ortiz, Guelaguetza; Chen, Weiping; Xu, Xiaoling; Deng, Chu-Xia

2016-01-01

Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target. ATP7A is a copper ATPase transporter responsible for intercellular movement and sequestering of cisplatin. Pharmaceutical replacement for ATP7A by ammonium tetrathiomolybdate (TM) enhanced cisplatin treatment in breast cancer cells. Allograft and xenograft models in athymic nude mice treated with cisplatin/TM exhibited retarded tumor growth, reduced accumulation of cancer stem cells and decreased cell proliferation as compared to mono-treatment with cisplatin or TM. Cisplatin/TM treatment of cisplatin-resistant tumors reduced ATP7A protein levels, attenuated cisplatin sequestering by ATP7A, increased nuclear availability of cisplatin, and subsequently enhanced DNA damage and apoptosis. Microarray analysis of gene ontology pathways that responded uniquely to cisplatin/TM double treatment depicted changes in cell cycle regulation, specifically in the G1/S transition. These findings offer the potential to combat platinum-resistant tumors and sensitize patients to conventional breast cancer treatment by identifying and targeting the resistant tumors' unique molecular adaptations. PMID:27806319

A Follow-up of a National Cohort of Breast Disease Factors Affecting the Development of Breast Cancer.

DTIC Science & Technology

1996-09-01

The study is based on a twelve-year follow-up of the cohort of 3500 women histologically diagnosed nationwide for benign and malignant breast lesions...between US whites and Africans. This study offers a unique opportunity to evaluate the progression of benign and malignant breast disease on a whole community base population.

Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

PubMed Central

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes. PMID:25264628

Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

PubMed

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes.

Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs.

PubMed

Knutson, Todd P; Truong, Thu H; Ma, Shihong; Brady, Nicholas J; Sullivan, Megan E; Raj, Ganesh; Schwertfeger, Kathryn L; Lange, Carol A

2017-04-17

Estrogen and progesterone are potent breast mitogens. In addition to steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and progesterone receptor (PR) actions via posttranslational events. Protein kinases commonly activated in breast cancers phosphorylate steroid hormone receptors (SRs) and profoundly impact their activities. To better understand the role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs in 209 human breast tumors represented on 2754 individual tissue spots within a tissue microarray and assayed the regulation of this site in human tumor explants cultured ex vivo. To complement this analysis, we assayed PR target gene regulation in T47D luminal breast cancer models following treatment with progestin (promegestone; R5020) and antiprogestins (mifepristone, onapristone, or aglepristone) in conditions under which the receptor is regulated by Lys388 SUMOylation (K388 intact) or is SUMO-deficient (via K388R mutation to mimic persistent Ser294 phosphorylation). Selected phospho-PR-driven target genes were validated by qRT-PCR and following RUNX2 shRNA knockdown in breast cancer cell lines. Primary and secondary mammosphere assays were performed to implicate phospho-Ser294 PRs, epidermal growth factor signaling, and RUNX2 in breast cancer stem cell biology. Phospho-Ser294 PR species were abundant in a majority (54%) of luminal breast tumors, and PR promoter selectivity was exquisitely sensitive to posttranslational modifications. Phospho-PR expression and target gene programs were significantly associated with invasive lobular carcinoma (ILC). Consistent with our finding that activated phospho-PRs undergo rapid ligand-dependent turnover, unique phospho-PR gene signatures were most prevalent in breast tumors clinically designated as PR-low to PR-null (luminal B) and included gene sets associated with cancer stem cell biology (HER2, PAX2, AHR, AR, RUNX). Validation studies demonstrated a requirement for RUNX2 in the regulation of selected phospho-PR target genes (SLC37A2). In vitro mammosphere formation assays support a role for phospho-Ser294-PRs via growth factor (EGF) signaling as well as RUNX2 as potent drivers of breast cancer stem cell fate. We conclude that PR Ser294 phosphorylation is a common event in breast cancer progression that is required to maintain breast cancer stem cell fate, in part via cooperation with growth factor-initiated signaling pathways and key phospho-PR target genes including SLC37A2 and RUNX2. Clinical measurement of phosphorylated PRs should be considered a useful marker of breast tumor stem cell potential. Alternatively, unique phospho-PR target gene sets may provide useful tools with which to identify patients likely to respond to selective PR modulators that block PR Ser294 phosphorylation as part of rational combination (i.e., with antiestrogens) endocrine therapies designed to durably block breast cancer recurrence.

Diffusion-weighted Breast MRI: Clinical Applications and Emerging Techniques

PubMed Central

Partridge, Savannah C.; Nissan, Noam; Rahbar, Habib; Kitsch, Averi E.; Sigmund, Eric E.

2016-01-01

Diffusion weighted MRI (DWI) holds potential to improve the detection and biological characterization of breast cancer. DWI is increasingly being incorporated into breast MRI protocols to address some of the shortcomings of routine clinical breast MRI. Potential benefits include improved differentiation of benign and malignant breast lesions, assessment and prediction of therapeutic efficacy, and non-contrast detection of breast cancer. The breast presents a unique imaging environment with significant physiologic and inter-subject variations, as well as specific challenges to achieving reliable high quality diffusion weighted MR images. Technical innovations are helping to overcome many of the image quality issues that have limited widespread use of DWI for breast imaging. Advanced modeling approaches to further characterize tissue perfusion, complexity, and glandular organization may expand knowledge and yield improved diagnostic tools. PMID:27690173

Greater absolute risk for all subtypes of breast cancer in the US than Malaysia.

PubMed

Horne, Hisani N; Beena Devi, C R; Sung, Hyuna; Tang, Tieng Swee; Rosenberg, Philip S; Hewitt, Stephen M; Sherman, Mark E; Anderson, William F; Yang, Xiaohong R

2015-01-01

Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.

Breast Cancer Treatment: Experiences of Changes and Social Stigma Among Thai Women in Southern Thailand.

PubMed

Suwankhong, Dusanee; Liamputtong, Pranee

2016-01-01

Women with breast cancer receive different forms of treatment. Although treatment can save the lives of women, they can result in adverse physical, psychological, and social effects that can impact the women's quality of life. The objective of this study was to describe the experiences of breast cancer treatment among Thai women in southern Thailand. This study used qualitative methods (in-depth interviewing and drawings) with 20 Thai women who had been diagnosed with breast cancer. Data were analyzed using thematic analysis methods. Three themes emerged: (a) being a breast cancer patient: visible signs and adverse effects of therapy, (b) experiencing emotional chaos, and (c) experiencing social dysfunction. The women had to deal with physical body changes, emotional burden, treatment-related social stigma, and being marginalized within their own social context. Women experienced changes including social stigma after receiving breast cancer treatments. They had to manage stigma and difficulties themselves without sufficient professional support. It is important for nurses to understand such experiences so that they may support appropriate coping strategies suited to each woman. Community health nurses need to view each woman with breast cancer as a unique person and appreciate how to provide appropriate care and support based on each woman's experience with her illness and treatment.

BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.

PubMed Central

Stoppa-Lyonnet, D; Laurent-Puig, P; Essioux, L; Pagès, S; Ithier, G; Ligot, L; Fourquet, A; Salmon, R J; Clough, K B; Pouillart, P; Bonaïti-Pellié, C; Thomas, G

1997-01-01

An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious. Images Figure 2 Figure 3 PMID:9150149

A Unique Opportunity To Test Whether Cell Fusion Is a Mechanism of Breast Cancer Metastasis

DTIC Science & Technology

2016-08-01

mesenchymal stem cells are a potent fusion partner for breast cancer cells ...and hematopoietic stem cells were enriched. In addition, human mesenchymal stem cells were obtained from bone marrow. 2   Table 1...adherent cell types – mesenchymal stem cells and epithelial cell types. Thus, MSCs were mixed with each epithelial cell type  (i.e. MSCs with

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

Cancer.gov

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center: a unique resource for defining the "molecular histology" of the breast.

PubMed

Sherman, Mark E; Figueroa, Jonine D; Henry, Jill E; Clare, Susan E; Rufenbarger, Connie; Storniolo, Anna Maria

2012-04-01

"Molecular histology" of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website. 2012 AACR

Quality of online information to support patient decision-making in breast cancer surgery.

PubMed

Bruce, Jordan G; Tucholka, Jennifer L; Steffens, Nicole M; Neuman, Heather B

2015-11-01

Breast cancer patients commonly use the internet as an information resource. Our objective was to evaluate the quality of online information available to support patients facing a decision for breast surgery. Breast cancer surgery-related queries were performed (Google and Bing), and reviewed for content pertinent to breast cancer surgery. The DISCERN instrument was used to evaluate websites' structural components that influence publication reliability and ability of information to support treatment decision-making. Scores of 4/5 were considered "good." 45 unique websites were identified. Websites satisfied a median 5/9 content questions. Commonly omitted topics included: having a choice between breast conservation and mastectomy (67%) and potential for 2nd surgery to obtain negative margins after breast conservation (60%). Websites had a median DISCERN score of 2.9 (range 2.0-4.5). Websites achieved higher scores on structural criteria (median 3.6 [2.1-4.7]), with 24% rated as "good." Scores on supporting decision-making questions were lower (2.6 [1.3-4.4]), with only 7% scoring "good." Although numerous breast cancer-related websites exist, most do a poor job providing women with essential information necessary to actively participate in decision-making for breast cancer surgery. Providing easily- accessible, high-quality online information has the potential to significantly improve patients' experiences with decision-making. © 2015 Wiley Periodicals, Inc.

Metaplastic carcinoma of the breast with mesenchymal differentiation (carcinosarcoma). A unique presentation of an aggressive malignancy and literature review.

PubMed

Salemis, Nikolaos S

2018-01-01

Metaplastic carcinoma of the breast with mesenchymal differentiation (MCMD), previously known as carcinosarcoma, is a very rare and aggressive tumor that has been recently classified as a subtype of metaplastic breast carcinoma. It accounts for 0.08%-0.2% of all breast cancers, with only a few cases reported in the literature. Histologically, MCMD is characterized by a biphasic pattern of malignant epithelial and sarcomatous components without evidence of a transition zone between the two elements. We herein describe a unique case of metaplastic carcinoma of the breast with chondrosarcomatous differentiation in a postmenopausal woman who presented with a large, rapidly growing, ulcerated, bleeding mass and signs of impending sepsis. Metaplastic breast carcinomas (MBC) are rare and aggressive tumors. They are characterized by larger size, lower rates of axillary node involvement, higher rates of triple negativity and distal metastases, earlier local recurrence and poorer survival compared with classic invasive breast cancer. Because of the rarity of MBC, the optimal treatment has not been well defined. Surgery is the main curative treatment modality since MBC has shown a suboptimal response to standard chemotherapy. Patients with MBC may be appropriate candidates for novel targeted therapies.

Addressing the unique psychosocial barriers to breast cancer treatment experienced by African-American women through integrative navigation.

PubMed

Chatman, Michelle C; Green, Rodney D

2011-12-01

African-American women face a disproportionally high breast cancer mortality rate and a significantly low five-year survival rate after breast cancer treatment. This study investigated, through a series of focus groups, how 32 African-American women (N = 32) breast cancer patients and survivors managed their cancer-related health needs. Participants also reported important barriers to care including problematic interactions with medical professionals, challenges in intimate relations, difficulties in handling the stigma and myths about breast cancer, and the psychological challenges that they faced. A patient navigation model was implemented at an eastern urban hospital that emphasized integrative therapies such as meditation, nutritional instruction, and yoga. Follow-up telephone interviews with 37 additional African-American participants (N = 37) indicated the rating of effectiveness to be at 3.8 to 3.9 out of 4 for the integrative patient navigation program. Over half of the survivors reported using some complementary techniques after treatment was completed, thus suggesting a long-term improvement in their quality of life as a result of the integrative techniques.

'We've fallen into the cracks': Aboriginal women's experiences with breast cancer through photovoice.

PubMed

Poudrier, Jennifer; Mac-Lean, Roanne Thomas

2009-12-01

Despite some recognition that Aboriginal women who have experienced breast cancer may have unique health needs, little research has documented the experiences of Aboriginal women from their perspective. Our main objective was to explore and to begin to make visible Aboriginal women's experiences with breast cancer using the qualitative research technique, photovoice. The research was based in Saskatchewan, Canada and participants were Aboriginal women who had completed breast cancer treatment. Although Aboriginal women cannot be viewed as a homogeneous group, participants indicated two areas of priority for health-care: (i) Aboriginal identity and traditional beliefs, although expressed in diverse ways, are an important dimension of breast cancer experiences and have relevance for health-care; and (ii) there is a need for multidimensional support which addresses larger issues of racism, power and socioeconomic inequality. We draw upon a critical and feminist conception of visuality to interrogate and disrupt the dominant visual terrain (both real and metaphorical) where Aboriginal women are either invisible or visible in disempowering ways. Aboriginal women who have experienced breast cancer must be made visible within health-care in a way that recognizes their experiences situated within the structural context of marginalization through colonial oppression.

The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development

DTIC Science & Technology

2015-09-01

intrinsic subtypes: basal-like (BL), claudin-low (CL), Her2+ (H2), luminal A (LA), luminal B (LB), and normal breast-like ( NBL ), each of which has...normal breast-like ( NBL ), each of which has unique biologic and prognostic features (28). Of these subtypes of breast cancer, the CL subtype is

Innovation in survivor care: group visits.

PubMed

Trotter, Kathryn; Frazier, Alana; Hendricks, Colleen K; Scarsella, Heidi

2011-04-01

The Centering Cancer Survivorship (CCS) follow-up care program is an innovation in healthcare delivery that meets the needs of cancer survivors and cancer centers. Piloted in a breast cancer clinic, the program provides an avenue for provision of psychological support and health-promotion activities, as well as surveillance for recurrence or late effects. The program empowers each survivor by enlisting her to produce a written breast cancer survivorship care plan for personal use and to share with her primary care provider. Concurrently, this innovation should enhance the viability of the primary cancer center by freeing appointment slots for oncologists who provide expensive therapies to newly diagnosed patients. The CCS program's central feature is the implementation of a multidisciplinary clinic designated specifically for breast cancer survivors in which follow-up care is provided through a group visit medical model. This model of care provides opportunities for health assessment, patient empowerment, and patient education within a framework of social support from peers with similar issues. The group visit model may be well suited to addressing the unique chronic healthcare needs of breast cancer survivors. Further evaluation is needed to verify cost-benefit analysis.

Recent Advances in Antibody-Drug Conjugates for Breast Cancer Treatment.

PubMed

Deng, Shanshan; Lin, Zongtao; Li, Wei

2017-01-01

Breast cancer is the most common cancer in women, with roughly half a million deaths per year worldwide. Among various approaches for breast cancer treatment, chemotherapy is predominantly used for patients at stages II-IV, and monoclonal antibody (mAb) therapy is used for patients with human epidermal growth factor receptor 2 (HER2) overexpression. Integrating the tumor specificity provided by unique mAbs and cytotoxicity of small molecule drugs, antibody-drug conjugates (ADCs) are a series of smart chemotherapeutics that have recently shown great promise in treating a number of cancer types. ADCs are designed to selectively attack and kill cancer cells with minimal toxicity to normal tissues. Ado-Trastuzumab emtansine (T-DM1) was the first and only ADC approved by the US Food and Drug Administration for HER2-positive breast cancer. Following the success of T-DM1, many novel ADCs have been developed, and their anticancer efficacies are currently undergoing preclinical or clinical investigation. The development of ADCs is a rapidly progressing field, and this review aims to summarize the most recent advances in ADCs targeting breast cancer over the past five years (2011-2016). The review highlights compositions and mechanisms of action of these newly developed ADCs and discusses current challenges and future directions of developing new ADCs for improved treatment of breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Consensus Recommendations for Advancing Breast Cancer: Risk Identification and Screening in Ethnically Diverse Younger Women

PubMed Central

Stojadinovic, Alexander; Summers, Thomas A; Eberhardt, John; Cerussi, Albert; Grundfest, Warren; Peterson, Charles M.; Brazaitis, Michael; Krupinski, Elizabeth; Freeman, Harold

2011-01-01

A need exists for a breast cancer risk identification paradigm that utilizes relevant demographic, clinical, and other readily obtainable patient-specific data in order to provide individualized cancer risk assessment, direct screening efforts, and detect breast cancer at an early disease stage in historically underserved populations, such as younger women (under age 40) and minority populations, who represent a disproportionate number of military beneficiaries. Recognizing this unique need for military beneficiaries, a consensus panel was convened by the USA TATRC to review available evidence for individualized breast cancer risk assessment and screening in young (< 40), ethnically diverse women with an overall goal of improving care for military beneficiaries. In the process of review and discussion, it was determined to publish our findings as the panel believes that our recommendations have the potential to reduce health disparities in risk assessment, health promotion, disease prevention, and early cancer detection within and in other underserved populations outside of the military. This paper aims to provide clinicians with an overview of the clinical factors, evidence and recommendations that are being used to advance risk assessment and screening for breast cancer in the military. PMID:21509152

Prediction of near-term breast cancer risk using a Bayesian belief network

NASA Astrophysics Data System (ADS)

Zheng, Bin; Ramalingam, Pandiyarajan; Hariharan, Harishwaran; Leader, Joseph K.; Gur, David

2013-03-01

Accurately predicting near-term breast cancer risk is an important prerequisite for establishing an optimal personalized breast cancer screening paradigm. In previous studies, we investigated and tested the feasibility of developing a unique near-term breast cancer risk prediction model based on a new risk factor associated with bilateral mammographic density asymmetry between the left and right breasts of a woman using a single feature. In this study we developed a multi-feature based Bayesian belief network (BBN) that combines bilateral mammographic density asymmetry with three other popular risk factors, namely (1) age, (2) family history, and (3) average breast density, to further increase the discriminatory power of our cancer risk model. A dataset involving "prior" negative mammography examinations of 348 women was used in the study. Among these women, 174 had breast cancer detected and verified in the next sequential screening examinations, and 174 remained negative (cancer-free). A BBN was applied to predict the risk of each woman having cancer detected six to 18 months later following the negative screening mammography. The prediction results were compared with those using single features. The prediction accuracy was significantly increased when using the BBN. The area under the ROC curve increased from an AUC=0.70 to 0.84 (p<0.01), while the positive predictive value (PPV) and negative predictive value (NPV) also increased from a PPV=0.61 to 0.78 and an NPV=0.65 to 0.75, respectively. This study demonstrates that a multi-feature based BBN can more accurately predict the near-term breast cancer risk than with a single feature.

Progesterone receptor modulates estrogen receptor-α action in breast cancer

PubMed Central

Mohammed, Hisham; Russell, I. Alasdair; Stark, Rory; Rueda, Oscar M.; Hickey, Theresa E.; Tarulli, Gerard A.; Serandour, Aurelien A. A.; Birrell, Stephen N.; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V.; Brown, Gordon D.; D’Santos, Clive; Robinson, Jessica L. L.; Silva, Grace; Launchbury, Rosalind; Perou, Charles M.; Stingl, John; Caldas, Carlos; Tilley, Wayne D.; Carroll, Jason S.

2015-01-01

Summary Progesterone receptor (PR) expression is employed as a biomarker of estrogen receptor-α (ERα) function and breast cancer prognosis. We now show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited estrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumour explants and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PgR is a common feature in ERα+ breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions. PMID:26153859

Breast Cancer Survivorship: A Comprehensive Review of Long-Term Medical Issues and Lifestyle Recommendations

PubMed Central

Bodai, Balazs I; Tuso, Phillip

2015-01-01

Long-term survival rates after a diagnosis of breast cancer are steadily rising. This is good news, but clinicians must also recognize that this brings new challenges to the medical community. As breast cancer becomes a chronic condition rather than a life-threatening illness owing to advances in early diagnosis and more effective treatments, health care practitioners must recognize and manage the long-term sequelae of the constellation of therapeutic modalities. Survivors of breast cancer represent a unique and extremely complex group of patients; not only do they have the challenge of dealing with multiple long-term side effects of treatment protocols, but many are also forced to address the preexisting comorbidities of their therapies, which often include multiple other issues. Therapies have additional and/or additive side effects that may interfere with treatments directed toward the new primary diagnosis of breast cancer. Our mandate is to establish a smooth transition from patient with breast cancer to survivor of breast cancer while providing ongoing and future guidance. Certainly, the information and resources to accomplish this transition are readily available; however, they are scattered throughout the literature and therefore are not easily accessible or available to the primary care physician. It is imperative that the information available regarding survivorship issues be accessible in an organized and useful format. This article is a modest attempt to provide a comprehensive review of the long-term medical issues relevant to survivorship after the diagnosis and treatment of breast cancer. A predicted shortage of oncologists by 2020 is well-recognized. Therefore, the bulk of long-term care will become dependent on the primary care physician. This shift of care means that these physicians will need to be well educated in the long-term medical issues related to breast cancer treatment. PMID:25902343

Recombinant nanocomposites by the clinical drugs of Abraxane® and Herceptin® as sequentially dual-targeting therapeutics for breast cancer.

PubMed

Ding, Shuang; Xiong, Jian; Lei, Dan; Zhu, Xiao-Li; Zhang, Hai-Jun

2018-01-01

Breast cancer greatly threatens the health of women all over the word despite of several effective drugs. Targeted therapy for breast cancer is limited to human epidermal growth factor receptor 2 (HER2). Herceptin ® , monoclonal antibody against HER2, is now widely used in HER2(+) breast cancer. Abraxane ® , the current gold standard for paclitaxel (PTX) delivery, has shown superiority in breast cancer based on nanoparticle albumin bound technology. Despite these advances, further novel targeted therapy with more improved anti-tumor efficacy for breast cancer is still urgently needed. Here, we report the recombinant nanocomposites (NPs) composed of the above two clinical drugs of Abraxane ® and Herceptin ® (Abra/anti-HER2), which at first migrates to the tumor region through the unique targeting mechanism of human serum albumin (HSA) of Abraxane ® , and sequentially further precisely recognize the HER2(+) breast cancer cells due to Herceptin ® . The Abra/anti-HER2 NPs were fabricated by a "one-step" synthesis using EDC/NHS. In vitro analysis of cell viability, apoptosis and cell cycle revealed that Abra/anti-HER2 NPs showed more anti-tumor efficacy against HER2(+) SK-BR-3 cells than Abraxane ® at equivalent PTX concentration. In addition, in HER2(+) breast cancer xenograft model, Abra/anti-HER2 NPs significantly inhibited tumor growth with less side effects. Moreover, the properties of more precise target and delayed release of PTX were proved by NIRF imaging. Thus, our results indicate that Abra/anti-HER2 NPs could represent a next-generation sequentially dual-targeting therapeutic agent for HER2(+) breast cancer.

Minority stress, psychosocial resources, and psychological distress among sexual minority breast cancer survivors

PubMed Central

Kamen, Charles; Jabson, Jennifer M.; Mustian, Karen M.; Boehmer, Ulrike

2017-01-01

Objective Few studies have examined unique factors predicting psychological distress among sexual minority (i.e., lesbian and bisexual) women post breast cancer diagnosis. The present study assessed the association of minority stress and psychosocial resource factors with depression and anxiety symptoms among sexual minority breast cancer survivors. Methods 201 sexual minority women who had ductal carcinoma in situ (DCIS) or stage I-IV breast cancer participated in this study through the Love/Avon Army of Women (AOW). Self-report questionnaires were used to assess demographic and clinical factors, minority stress factors (discrimination, minority identity development, outness), psychosocial resources (resilience, social support), and psychological distress (anxiety and depression). These factors were included in a structural equation model, testing psychosocial resources as mediators between minority stress and psychological distress. Results There were no significant differences noted between lesbian and bisexual women. The final structural equation model demonstrated acceptable fit across all sexual minority women, χ2 = 27.83, p > 0.05; confirmatory fit index = 0.97, root-mean-square error of approximation = 0.04, Tucker-Lewis Index = 0.93. The model accounted for significant variance in psychological distress (56%). Examination of indirect effects confirmed that exposure to discrimination was associated with distress via association with resilience. Conclusions Factors unique to sexual minority populations, such as minority stress, may be associated with higher rates of psychological distress among sexual minority breast cancer survivors. However, presence of psychosocial resources may mediate relationships with distress in this population; enhancement of resilience, in particular, could be an aim of psychological intervention. PMID:28165265

Understanding Barriers and Facilitators to Breast and Cervical Cancer Screening among Muslim Women in New York City: Perspectives from Key Informants.

PubMed

Islam, Nadia; Patel, Shilpa; Brooks-Griffin, Quanza; Kemp, Patrice; Raveis, Victoria; Riley, Lindsey; Gummi, Sindhura; Nur, Potrirankamanis Queano; Ravenell, Joseph; Cole, Helen; Kwon, Simona

2017-01-01

Muslims are one of the fastest growing religious groups in the US. However, little is known about their health disparities, and how their unique cultural, religious, and social beliefs and practices affect health behaviors and outcomes. Studies demonstrate Muslim women may have lower rates of breast and cervical cancer screening compared to the overall population. The purpose of this study was to: 1) conduct key-informant interviews with Muslim community leaders in New York City (NYC), to understand contextual factors that impact Muslim women's beliefs and practices regarding breast and cervical cancer screening; and 2) inform the development and implementation of a research study on breast and cervical cancer screening among Muslims. Twelve key-informant interviews were conducted. The sample included imams, female religious leaders, physicians, community-based organization leaders, and social service representatives. The interview guide assessed: 1) unique healthcare barriers faced by Muslim women; 2) cultural and social considerations in conducting research; 3) potential strategies for increasing screening in this population; and 4) content and venues for culturally tailored programming and messaging. Key informants noted structure and culture as barriers and religion as a facilitator to breast and cervical cancer screening. Themes regarding the development of targeted health campaigns to increase screening included the importance of educational and in-language materials and messaging, and engaging mosques and religious leaders for dissemination. Although Muslim women face a number of barriers to screening, religious beliefs and support structures can be leveraged to facilitate screening and enhance the dissemination and promotion of screening.

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development).

PubMed

Dickersin, K; Braun, L; Mead, M; Millikan, R; Wu, A M; Pietenpol, J; Troyan, S; Anderson, B; Visco, F

2001-12-01

To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists. Students were breast cancer activists and other consumers, mainly affiliated with advocacy organizations in the United States of America. Project LEAD is offered by the National Breast Cancer Coalition; the course takes place over 5 days and is offered 4 times a year, in various cities in the United States of America. The Project LEAD curriculum has developed over 5 years to include lectures, problem-based study groups, case studies, interactive critical appraisal sessions, a seminar by an 'expert' scientist, role play, and homework components. A core faculty has been valuable for evaluating and revising the course and has proved necessary to provide consistent high quality teaching. Course evaluations indicated that students gained critical appraisal skills, enhanced their knowledge and developed confidence in selected areas of basic science and epidemiology. Project LEAD comprises a unique curriculum for training breast cancer activists in science and critical appraisal. Course evaluations indicate that students gain confidence and skills from the course.

Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters

PubMed Central

Darash-Yahana, Merav; Pozniak, Yair; Lu, Mingyang; Sohn, Yang-Sung; Karmi, Ola; Tamir, Sagi; Bai, Fang; Song, Luhua; Jennings, Patricia A.; Pikarsky, Eli; Geiger, Tamar; Onuchic, José N.; Mittler, Ron; Nechushtai, Rachel

2016-01-01

Iron–sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the NAF-1 cluster, NAF-1(H114C), in xenograft breast cancer tumors results in a dramatic decrease in tumor size that is accompanied by enhanced mitochondrial iron and reactive oxygen accumulation and reduced cellular tolerance to oxidative stress. Furthermore, treating breast cancer cells with pioglitazone that stabilizes the 3Cys-1His cluster of NAF-1 results in a similar effect on mitochondrial iron and reactive oxygen species accumulation. Taken together, our findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. Cluster transfer reactions mediated by the overexpressed NAF-1 protein are therefore critical for inducing oxidative stress tolerance in cancer cells, leading to rapid tumor growth, and drugs that stabilize the NAF-1 cluster could be used as part of a treatment strategy for cancers that display high NAF-1 expression. PMID:27621439

Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters.

PubMed

Darash-Yahana, Merav; Pozniak, Yair; Lu, Mingyang; Sohn, Yang-Sung; Karmi, Ola; Tamir, Sagi; Bai, Fang; Song, Luhua; Jennings, Patricia A; Pikarsky, Eli; Geiger, Tamar; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel

2016-09-27

Iron-sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the NAF-1 cluster, NAF-1(H114C), in xenograft breast cancer tumors results in a dramatic decrease in tumor size that is accompanied by enhanced mitochondrial iron and reactive oxygen accumulation and reduced cellular tolerance to oxidative stress. Furthermore, treating breast cancer cells with pioglitazone that stabilizes the 3Cys-1His cluster of NAF-1 results in a similar effect on mitochondrial iron and reactive oxygen species accumulation. Taken together, our findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. Cluster transfer reactions mediated by the overexpressed NAF-1 protein are therefore critical for inducing oxidative stress tolerance in cancer cells, leading to rapid tumor growth, and drugs that stabilize the NAF-1 cluster could be used as part of a treatment strategy for cancers that display high NAF-1 expression.

Barriers to rehabilitative care for young breast cancer survivors: a qualitative understanding.

PubMed

Miedema, Baukje; Easley, Julie

2012-06-01

The goal of this study was to assess the rehabilitation needs of young women breast cancer survivors under the age of 50 and to identify factors that may impact or prevent cancer rehabilitation utilization. Utilizing a grounded theory methodology, 35 young breast cancer survivors were interviewed twice in four Atlantic Canadian provinces. A considerable number of barriers exist to receiving rehabilitative care post-treatment for young breast cancer survivors. The systemic barriers include the lack of availability of services, travel issues, cost of services, and the lack of support to address the unique needs for this age group. However, the most complicated barriers to accessing rehabilitative care were personal barriers which related more to choice and circumstances, such as the lack of time due to family responsibilities and appointment fatigue. Many of these personal barriers were rooted in the complex set of gender roles of young women as patients, mothers, workers, and caregivers. The contexts of young women's lives can have a substantial impact on their decisions to seek and receive rehabilitative care after breast cancer treatment. The systemic barriers can be reduced by introducing more services or financial assistance; however, the personal barriers to rehabilitation services are difficult to ameliorate due to the complex set of roles within and outside the family for this group of young breast cancer survivors. Health care providers need to take into consideration the multiple contexts of women's lives when developing and promoting breast cancer rehabilitation services and programs.

The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center: A Unique Resource for Defining the “Molecular Histology” of the Breast

PubMed Central

Sherman, Mark E.; Figueroa, Jonine D.; Henry, Jill E.; Clare, Susan E.; Rufenbarger, Connie; Storniolo, Anna Maria

2014-01-01

“Molecular histology” of the breast may be conceptualized as encompassing the normative ranges of histological structure and marker expression in normal breast tissues in relation to a woman’s age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin fixed paraffin embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank’s website. PMID:22345117

Understanding health anxiety following breast cancer diagnosis.

PubMed

Jones, Shannon L; Hadjistavropoulos, Heather D; Gullickson, Kirsten

2014-01-01

Health anxiety is a persistent fear of illness or disease that often involves the misinterpretation of bodily symptoms as signs of serious illness. Evidence shows that health anxiety affects a proportion of women following a diagnosis of breast cancer, but there are some limitations to how health anxiety has been measured. The objectives of this study were to (1) provide an estimate of clinically elevated health anxiety in women after a diagnosis of breast cancer using a validated measure appropriate for medical populations and (2) understand patient, disease, and anxiety/vulnerability variables that predict health anxiety in this group. Canadian women (n = 137) diagnosed with breast cancer within the past five years completed an online survey measuring health anxiety, along with patient, disease, and anxiety/vulnerability variables. Clinically significant health anxiety was reported by 23.4% of the sample. The regression model revealed that younger age, more advanced stage of breast cancer, increased cognitive anxiety sensitivity, and greater body vigilance were significant unique predictors of health anxiety. These findings highlight that a proportion of women report substantial health anxiety following breast cancer diagnosis, with a combination of patient, disease, and anxiety/vulnerability variables associated with the experience. Further research is needed to better understand the impact of health anxiety in this population.

From adolescent daughter to mother: exploring message design strategies for breast and cervical cancer prevention and screening.

PubMed

Mosavel, Maghboeba; Genderson, Maureen Wilson

2013-09-01

Early detection of breast and cervical cancers is one preventive behavior that may provide the adolescent daughter with a unique opportunity to provide encouragement to her mother or guardian to obtain screening. This study explored the design strategies necessary for developing an effective daughter-initiated message about screening for breast and cervical cancers. Thirty-two (N = 64) African-American mother-daughter dyads were interviewed about parenting style, goodwill, and daughters' credibility and risk behaviors that might influence receptivity toward a screening appeal. Mothers indicated that a tailored, emotional appeal combined with cancer facts delivered in a private setting would be most effective. Daughters were perceived as highly credible messengers and were perceived to have high levels of goodwill toward their mothers, regardless of risk behaviors.

Young Women with Breast Cancer: A Focus Group Study of Unmet Needs.

PubMed

Ruddy, Kathryn J; Greaney, Mary L; Sprunck-Harrild, Kim; Meyer, Meghan E; Emmons, Karen M; Partridge, Ann H

2013-12-01

Purpose: Young women with breast cancer suffer distress both at the time of diagnosis and afterwards. This study aimed to elucidate which issues are most disturbing to this population and which might be amenable to intervention. Methods: English-speaking women treated or involved in research at the Dana-Farber Cancer Institute for stage I-III breast cancer while aged 18-42 years were invited to participate in one of four focus groups. A trained moderator led each 90-minute audio-recorded group using a semi-structured interview guide. All transcripts were coded using thematic content analysis with NVivo software. Results: Thirty-six women participated. Three major themes emerged from the analyses of these focus groups' data: (1) participants felt different from older breast cancer patients with regard to relationships, fertility, menopausal symptoms, treatment side effects, and work/finances; (2) participants faced unique challenges transitioning into the survivorship phase of care; and (3) participants desired assistance, including connections with other young patients, help navigating the healthcare system, educational materials, and lists of appropriate counselors. Conclusion: Young women with breast cancer have unmet needs for psychosocial support, education, and symptom management, and can identify potential support that may help meet these needs.

Update on HER2 testing for breast and upper gastrointestinal tract cancers.

PubMed

Ross, Jeffrey S

2011-06-01

With the regulatory approvals in Europe and the USA of trastuzumab-based anti-HER2 targeted therapy for upper gastrointestinal cancers in 2010, HER2 testing has now become universal for newly diagnosed cases of both breast cancer and adenocarcinomas of esophagus, stomach and gastroesophageal origin. In the 12 years or more since the approval of trastuzumab for breast cancer, general refinements in approaches to HER2 testing, including a greater understanding of the implications of preanalytic factors impacting the test results and the application of standardization of reporting of HER2 test results, have taken place. There has also been continuing development in breast cancer with the introduction of new HER2 tests, including non-FISH tests, dimerization assays, phosphorylated HER2 receptor tests, mRNA-based tests, HER2 gene sequencing tests and the application of HER2 testing to circulating tumor cells. Most recently, the introduction of HER2 testing for upper gastrointentinal malignancies has emphasized the need for performing and interpreting slide-based assays in a manner unique to these specimens and not to apply the breast cancer testing protocols to esophageal and gastric adenocarcinomas.

Unique Characteristics of Adolescent and Young Adult Acute Lymphoblastic Leukemia, Breast Cancer, and Colon Cancer

PubMed Central

Seibel, Nita L.; Blair, Donald G.; Albritton, Karen; Hayes-Lattin, Brandon

2011-01-01

Each year in the United States, nearly 70 000 individuals between the ages of 15 and 40 years are diagnosed with cancer. Although overall cancer survival rates among pediatric and older adult patients have increased in recent decades, there has been little improvement in survival of adolescent and young adult (AYA) cancer patients since 1975 when collected data became adequate to evaluate this issue. In 2006, the AYA Oncology Progress Review Group made recommendations for addressing the needs of this population that were later implemented by the LIVESTRONG Young Adult Alliance. One of their overriding questions was whether the cancers seen in AYA patients were biologically different than the same cancers in adult and/or pediatric patients. On June 9–10, 2009, the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) convened a workshop in Bethesda, MD, entitled “Unique Characteristics of AYA Cancers: Focus on Acute Lymphocytic Leukemia (ALL), Breast Cancer and Colon Cancer” that aimed to examine the current state of basic and translational research on these cancers and to discuss the next steps to improve their prognosis and treatment. PMID:21436065

Breast cancer and screening information needs and preferred communication medium among Iranian immigrant women in Toronto.

PubMed

Vahabi, Mandana

2011-11-01

Few studies have investigated what information women from minority immigrant groups need about breast cancer and screening. Nor has much research been conducted about how such women would prefer to receive this information. Mere translation of breast cancer and screening information from generic materials, without considering and respecting women's unique historical, political, and cultural experiences, is insufficient. This study explored breast cancer and screening information needs and preferred methods of communication among Iranian immigrant women. A convenience sample of 50 women was recruited and interviewed over a 4-month period (June-September 2008); all resided in Toronto Canada, and had no history of breast cancer. Tape-recorded interviews were transcribed and analysed using a thematic analysis technique. While generic breast health communication focusing on physiological risk information meets some of the needs of Iranian immigrant women, results showed that the needs of this group go beyond this basic information. This group is influenced by historical, sociopolitical, and cultural experiences pre- and post-immigration. Their experiences with chemical war, unsafe physical environment (air and water pollution), and their sociopolitical situation appear to have limited their access to accurate and reliable breast cancer and screening information in their homeland. Moreover, the behavioural and psychosocial changes they face after immigration appear to have a strong influence on their breast cancer and screening information needs. Considering their limited time due to their multiple demands post-migration, multi-media methods were highly preferred as a communication means by this group. The results of this study can be used to guide the design and implementation of culturally sensitive breast health information. For instance, video presentations conducted by a trusted Iranian healthcare professional focusing on socioculturally relevant breast cancer risk factors, symptoms, and screening methods, as well as a list of available breast health resources, could improve Iranian women's knowledge and uptake of breast health practices. © 2011 Blackwell Publishing Ltd.

Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State

PubMed Central

Sherman, Recinda L.; Howlader, Nadia; Jemal, Ahmedin; Ryerson, A. Blythe; Henry, Kevin A.; Boscoe, Francis P.; Cronin, Kathleen A.; Lake, Andrew; Noone, Anne-Michelle; Henley, S. Jane; Eheman, Christie R.; Anderson, Robert N.; Penberthy, Lynne

2015-01-01

Background: The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data. Methods: Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. Results: Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. Overall mortality has been declining for both men and women since the early 1990’s and for children since the 1970’s. HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100000 non-Hispanic white women, respectively). HR+/HER2- breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100000 non-Hispanic black women), which is reflected in high rates in southeastern states. Conclusions: Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection standards to produce clinically relevant data based on evolving medical knowledge. PMID:25825511

Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State.

PubMed

Kohler, Betsy A; Sherman, Recinda L; Howlader, Nadia; Jemal, Ahmedin; Ryerson, A Blythe; Henry, Kevin A; Boscoe, Francis P; Cronin, Kathleen A; Lake, Andrew; Noone, Anne-Michelle; Henley, S Jane; Eheman, Christie R; Anderson, Robert N; Penberthy, Lynne

2015-06-01

The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data. Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011 [corrected]. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100000 non-Hispanic white women, respectively). HR+/HER2- breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100000 non-Hispanic black women), which is reflected in high rates in southeastern states. Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection standards to produce clinically relevant data based on evolving medical knowledge. © The Author 2015. Published by Oxford University Press.

Integrated analysis of breast cancer cell lines reveals unique signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised ofmore » 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.« less

Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

PubMed

Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

2009-01-01

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

Quality of life among immigrant Latina breast cancer survivors: realities of culture and enhancing cancer care.

PubMed

Lopez-Class, Maria; Perret-Gentil, Monique; Kreling, Barbara; Caicedo, Larisa; Mandelblatt, Jeanne; Graves, Kristi D

2011-12-01

Breast cancer is the most common cancer among Latinas. This study examined social, cultural, and health care system factors that impact the quality of life and survivorship experiences of Latina immigrant breast cancer survivors. We interviewed Latina breast cancer survivors (n = 19) and, based on the interview findings, conducted two focus groups (n = 9). Research staff translated transcripts from Spanish into English. Two trained raters reviewed the content and identified themes. Thematic content analysis was used to categorize and organize data. Participants were largely monolingual in Spanish, predominantly from Central and South America and most (68%) had lived in the U.S. for ten or more years. All women were diagnosed and treated in the U.S. and were an average of 3.1 years from diagnosis. Women's survivorship experiences appeared to be shaped by cultural beliefs and experiences as immigrants such as secrecy/shame about a breast cancer diagnosis, feelings of isolation, importance of family support (familism), challenges with developing social relationships in the U.S. (less personalismo), and, for some, their partner's difficulty with showing emotional support (machismo). Navigating the U.S. medical system and language barriers were additional challenges in the participants' health care interactions. Latina breast cancer survivors adhere to certain cultural values and face unique issues as immigrants, potentially influencing overall quality of life and doctor-patient communication. Efforts to improve Latina immigrant breast cancer survivors' quality of life could include increased assessment of psychosocial functioning and referral to social support services, culturally sensitive navigation programs, and consistent use of appropriately trained interpreters.

Providing and funding breast health services in urban nurse-managed health centers.

PubMed

Tsai, Pei-Yun; Peterman, Beth; Baisch, Mary Jo; Ji, Eun Sun; Zwiers, Kelly

2014-01-01

Nurse-managed health centers (NMHCs) are an innovative health care delivery model that serves as an important point of health care access for populations at risk for disparities in health outcomes. This article describes the process and outcomes of clinical breast health services in two NMHCs located in a large Midwestern city. Findings indicate that client's knowledge about breast health was increased after they received breast health services from NMHC nurses. Significant positive changes in behavior related to the early detection of breast cancer were found in the study. NMHCs, identified for expansion in the Patient Protection and Affordable Care Act, offer a unique health care services delivery model that promotes access to care and early identification of breast cancer in very low-income and uninsured women. Copyright © 2014 Elsevier Inc. All rights reserved.

A Unique Opportunity to Test Whether Cell Fusion is a Mechanism of Breast Cancer Metastasis

DTIC Science & Technology

2015-06-01

conditions for T47D and human mesenchymal stem cell populations. As a result we have been able to conduct our first co-culture experiments to determine...spontaneously and reliably with mesenchymal stem cells . We found that fusion occurs more frequently with hypoxia and that one means by which...in hypoxic conditions, we decided to investigate whether the mechanism of breast cancer cell fusion with mesenchymal stem /multipotent stromal cells

Unique Proteins Expressed by Blood Vessels in Skeletal Sites Colonized by Breast Cancer Cells

DTIC Science & Technology

2005-08-01

labeled acetylated LDL at an accelerated rate (3). After one week in culture BVECs and MVECs were harvested. Total RNA was extracted from both cell...bones where breast cancer cells tend to lodge, as compared to the vasculature of the central marrow cavity. We have found differences in RNA expression...by microarray analysis. The bone-derived vasculature expresses five RNA messages in greater abundance (2-fold or more) than the marrow-derived

Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women

PubMed Central

2013-01-01

Introduction Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women. Methods Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010. Results With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease. Conclusions Among AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women. PMID:24131591

Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

PubMed Central

Brandt-Rauf, Sherry I.; Raveis, Victoria H.; Drummond, Nathan F.; Conte, Jill A.; Rothman, Sheila M.

2006-01-01

We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay–Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815

IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity

PubMed Central

Chiang, Sarah; Weigelt, Britta; Wen, Huei-Chi; Pareja, Fresia; Raghavendra, Ashwini; Martelotto, Luciano G.; Burke, Kathleen A.; Basili, Thais; Li, Anqi; Geyer, Felipe C.; Piscuoglio, Salvatore; Ng, Charlotte K.Y.; Jungbluth, Achim A.; Balss, Jörg; Pusch, Stefan; Baker, Gabrielle M.; Cole, Kimberly S.; von Deimling, Andreas; Batten, Julie M.; Marotti, Jonathan D.; Soh, Hwei-Choo; McCalip, Benjamin L.; Serrano, Jonathan; Lim, Raymond S.; Siziopikou, Kalliopi P.; Lu, Song; Liu, Xiaolong; Hammour, Tarek; Brogi, Edi; Snuderl, Matija; Iafrate, A. John; Reis-Filho, Jorge S.; Schnitt, Stuart J.

2017-01-01

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. PMID:27913435

Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

PubMed

Nicolau, Monica; Levine, Arnold J; Carlsson, Gunnar

2011-04-26

High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

Understanding Barriers and Facilitators to Breast and Cervical Cancer Screening among Muslim Women in New York City: Perspectives from Key Informants

PubMed Central

Islam, Nadia; Patel, Shilpa; Brooks-Griffin, Quanza; Kemp, Patrice; Raveis, Victoria; Riley, Lindsey; Gummi, Sindhura; Nur, Potrirankamanis Queano; Ravenell, Joseph; Cole, Helen; Kwon, Simona

2017-01-01

Background Muslims are one of the fastest growing religious groups in the US. However, little is known about their health disparities, and how their unique cultural, religious, and social beliefs and practices affect health behaviors and outcomes. Studies demonstrate Muslim women may have lower rates of breast and cervical cancer screening compared to the overall population. Methods The purpose of this study was to: 1) conduct key-informant interviews with Muslim community leaders in New York City (NYC), to understand contextual factors that impact Muslim women’s beliefs and practices regarding breast and cervical cancer screening; and 2) inform the development and implementation of a research study on breast and cervical cancer screening among Muslims. Twelve key-informant interviews were conducted. The sample included imams, female religious leaders, physicians, community-based organization leaders, and social service representatives. The interview guide assessed: 1) unique healthcare barriers faced by Muslim women; 2) cultural and social considerations in conducting research; 3) potential strategies for increasing screening in this population; and 4) content and venues for culturally tailored programming and messaging. Results Key informants noted structure and culture as barriers and religion as a facilitator to breast and cervical cancer screening. Themes regarding the development of targeted health campaigns to increase screening included the importance of educational and in-language materials and messaging, and engaging mosques and religious leaders for dissemination. Conclusion Although Muslim women face a number of barriers to screening, religious beliefs and support structures can be leveraged to facilitate screening and enhance the dissemination and promotion of screening. PMID:29629435

MutYH mutation carriers have increased breast cancer risk.

PubMed

Rennert, Gad; Lejbkowicz, Flavio; Cohen, Ilana; Pinchev, Mila; Rennert, Hedy S; Barnett-Griness, Ofra

2012-04-15

Variants of the mutY homolog gene MutYH, a DNA repair gene, are associated with increased risk of colorectal cancer; however, it remains unclear whether these variants also are associated with the risk of other cancers. The authors studied the risk of breast cancer associated with MutYH variants in a unique ethnic group of Sephardi Jews in Israel with a high prevalence of MutYH mutations. The study participants were 930 Sephardi Jewish women of North African origin who were recruited into the population-based case-control Breast Cancer in Northern Israel Study (BCINIS) either as breast cancer cases or as healthy controls. All participants contributed a blood sample and completed an interview. Two MutYH variants, a glycine-to-aspartic acid substitution at codon 396 (G396D) and a tyrosine-to-cysteine substitution at codon 179 (Y179C), were studied. In the Sephardi Jews, among the healthy controls, 20 women (3.7%) were homozygote or heterozygote carriers of the G396D variant, and 4 women (0.7%) were heterozygote carriers of the Y179C variant. Breast cancer cases had a 6.7% prevalence of G396D, yielding a significantly elevated risk estimate for breast cancer (odds ratio, 1.86; 95% confidence interval, 1.02-3.39; P = .039). The tumors detected in carriers with MutYH variants were similar in characteristics to those without MutYH variants, as was the age at diagnosis. Carriers of variants in MutYH, although not very common, may have an increased risk of breast cancer in Jews of North African origin. Identification of such carriers and special surveillance protocols may be warranted. Copyright © 2011 American Cancer Society.

Mass spectrometry (LC-MS/MS) identified proteomic biosignatures of breast cancer in proximal fluid.

PubMed

Whelan, Stephen A; He, Jianbo; Lu, Ming; Souda, Puneet; Saxton, Romaine E; Faull, Kym F; Whitelegge, Julian P; Chang, Helena R

2012-10-05

We have begun an early phase of biomarker discovery in three clinically important types of breast cancer using a panel of human cell lines: HER2 positive, hormone receptor positive and HER2 negative, and triple negative (HER2-, ER-, PR-). We identified and characterized the most abundant secreted, sloughed, or leaked proteins released into serum free media from these breast cancer cell lines using a combination of protein fractionation methods before LC-MS/MS mass spectrometry analysis. A total of 249 proteins were detected in the proximal fluid of 7 breast cancer cell lines. The expression of a selected group of high abundance and/or breast cancer-specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis. Interestingly, mass spectrometry identified a cathepsin D protein single-nucleotide polymorphism (SNP) by alanine to valine replacement from the MCF-7 breast cancer cell line. Comparison of each cell line media proteome displayed unique and consistent biosignatures regardless of the individual group classifications, demonstrating the potential for stratification of breast cancer. On the basis of the cell line media proteome, predictive Tree software was able to categorize each cell line as HER2 positive, HER2 negative, and hormone receptor positive and triple negative based on only two proteins, muscle fructose 1,6-bisphosphate aldolase and keratin 19. In addition, the predictive Tree software clearly identified MCF-7 cell line overexpresing the HER2 receptor with the SNP cathepsin D biomarker.

Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds.

PubMed

Rennix, Christopher P; Quinn, Margaret M; Amoroso, Paul J; Eisen, Ellen A; Wegman, David H

2005-09-01

The military presents a unique opportunity to study the incidence of disease in a population with complete knowledge of person-time and occupation. Women in the Army are employed more frequently in non-traditional, industrial jobs such as auto mechanic and motor transport operators than in the general US population, increasing the probability of exposure to industrial chemicals. A cohort to investigate the risk of breast cancer among active duty Army women occupationally exposed to volatile organic chemicals (VOCs) was constructed. Age-adjusted incidence rates for breast cancer were calculated for more than 270,000 enlisted women who served between 1980-1996. Twenty-one VOCs, described in previously published literature as having a potential risk of breast cancer, were identified in an Army industrial hygiene survey database. Job title histories were linked to workplace chemical evaluations conducted by Army industrial hygienists, which included a subjective exposure potential rating (high, medium, low, and none) for each VOC. Poisson regression analysis was used to evaluate the association between the exposure rating by job title and breast cancer. The incidence of breast cancer in the cohort was significantly elevated in women younger than 35 years of age, especially among black women, when compared to the age-specific rates in the general population. Women who worked in occupations with a moderate to high exposure potential to at least one VOC had a 48% increased risk (P < 0.05) of breast cancer while on active duty between 1980-1996 when compared to those women with low to no exposure potential. This study provides preliminary evidence that exposure to one or more of the study VOCs is associated with an increased risk of breast cancer. Further substance-specific, quantitative analyses are warranted.

From Adolescent Daughter to Mother: Exploring Message Design Strategies for Breast and Cervical Cancer Prevention and Screening

PubMed Central

Mosavel, Maghboeba; Genderson, Maureen Wilson

2013-01-01

Early detection of breast and cervical cancers is one preventive behavior that may provide the adolescent daughter with a unique opportunity to provide encouragement to her mother or guardian to obtain screening. This study explored the design strategies necessary for developing an effective daughter-initiated message about screening for breast and cervical cancers. Thirty-two (N=64) African-American mother-daughter dyads were interviewed about parenting style, goodwill, and daughters’ credibility and risk behaviors that might influence receptivity toward a screening appeal. Mothers indicated that a tailored, emotional appeal combined with cancer facts delivered in a private setting would be most effective. Daughters were perceived as highly credible messengers and were perceived to have high levels of goodwill toward their mothers, regardless of risk behaviors. PMID:23813491

Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists.

PubMed

Mills, P K; Annegers, J F; Phillips, R L

1988-03-01

Seventh-day Adventist women experience lower mortality rates from breast cancer than other white females in the United States. To evaluate the role of diet in relation to breast cancer within this unique population (more than one-half of all Adventist women are lacto-ovo-vegetarians), a nested case-control study was conducted including 142 cases of fatal breast cancer and 852 matched controls among California Seventh-day Adventist women in 1960-1980. No significant relations between the consumption of animal products (meat, milk, cheese, and eggs) and breast cancer were evident. Odds ratios of 1.00, 1.22, and 1.03 were observed for meat consumption categories of none or occasional, 1-3 days/week, and 4+ days/week, respectively. However, among those women who experienced a relatively early age at natural menopause (less than or equal to 48 years), a suggestive though nonsignificant, positive association between meat consumption and risk was noted. These relations remained unchanged after simultaneously controlling for the effects of other covariates (menstrual characteristics and obesity) via conditional logistic regression analysis. Risk was not related to age at first exposure to the vegetarian lifestyle nor to duration of exposure to the vegetarian lifestyle.

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development)

PubMed Central

Dickersin, Kay; Braun, Lundy; Mead, Margaret; Millikan, Robert; Wu, Anna M.; Pietenpol, Jennifer; Troyan, Susan; Anderson, Benjamin; Visco, Frances

2008-01-01

Objective To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists. Population Students were breast cancer activists and other consumers, mainly affiliated with advocacy organizations in the United States of America. Setting Project LEAD is offered by the National Breast Cancer Coalition; the course takes place over 5 days and is offered 4 times a year, in various cities in the United States of America. Results The Project LEAD curriculum has developed over 5 years to include lectures, problem‐based study groups, case studies, interactive critical appraisal sessions, a seminar by an ‘expert’ scientist, role play, and homework components. A core faculty has been valuable for evaluating and revising the course and has proved necessary to provide consistent high quality teaching. Course evaluations indicated that students gained critical appraisal skills, enhanced their knowledge and developed confidence in selected areas of basic science and epidemiology. Conclusions Project LEAD comprises a unique curriculum for training breast cancer activists in science and critical appraisal. Course evaluations indicate that students gain confidence and skills from the course. PMID:11703495

Women's preferences for contralateral prophylactic mastectomy: An investigation using protection motivation theory.

PubMed

Tesson, Stephanie; Richards, Imogen; Porter, David; Phillips, Kelly-Anne; Rankin, Nicole; Musiello, Toni; Marven, Michelle; Butow, Phyllis

2016-05-01

Most women diagnosed with unilateral breast cancer without BRCA1 or BRCA2 mutations are at low risk of contralateral breast cancer. Contralateral Prophylactic Mastectomy (CPM) decreases the relative risk of contralateral breast cancer, but may not increase life expectancy; yet international uptake is increasing. This study applied protection motivation theory (PMT) to determine factors associated with women's intentions to undergo CPM. Three hundred eighty-eight women previously diagnosed with unilateral breast cancer and of negative or unknown BRCA1 or BRCA2 status were recruited from an advocacy group's research database. Participants completed measures of PMT constructs based on a common hypothetical CPM decision-making scenario. PMT constructs explained 16% of variance in intentions to undergo CPM. Response efficacy (CPM's advantages) and response costs (CPM's disadvantages) were unique individual predictors of intentions. Decision-making appears driven by considerations of the psychological, cosmetic and emotional advantages and disadvantages of CPM. Overestimations of threat to life from contralateral breast cancer and survival benefit from CPM also appear influential factors. Patients require balanced and medically accurate information regarding the pros and cons of CPM, survival rates, and recurrence risks to ensure realistic and informed decision-making.

C-Jun N-terminal Kinase and Apoptosis in Breast Cancer.

DTIC Science & Technology

1999-06-01

specific aim#l in the Statement of Work) Curcumin (diferuloylmethane), a dietary pigment from Curcuma longa , gives the golden-yellow color and unique...174 Curcumin (diferuloylmethane), a dietary pigment from Curcuma longa , gives the golden-yellow color and unique flavor to curry. The

Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries

PubMed Central

Kwong, Ava; Shin, Vivian Y; Ho, John C W; Kang, Eunyoung; Nakamura, Seigo; Teo, Soo-Hwang; Lee, Ann S G; Sng, Jen-Hwei; Ginsburg, Ophira M; Kurian, Allison W; Weitzel, Jeffrey N; Siu, Man-Ting; Law, Fian B F; Chan, Tsun-Leung; Narod, Steven A; Ford, James M; Ma, Edmond S K; Kim, Sung-Won

2015-01-01

Approximately 5%–10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer. PMID:26187060

The stressors and vulnerabilities of young single childless women with breast cancer: a qualitative study.

PubMed

Corney, Roslyn; Puthussery, Shuby; Swinglehurst, Jane

2014-02-01

Marital or partnership status is seldom investigated as a primary contributing factor to women's wellbeing after a diagnosis of breast cancer. It has been suggested, however, that single childless women with breast cancer may face unique stressors. This paper explores the stressors and vulnerabilities of young single childless women with a first episode of breast cancer. A qualitative descriptive method was used. As part of a larger study examining fertility concerns of young childless women with first episode of breast cancer, in-depth semi-structured interviews were conducted with 10 single women. Recorded interviews were analysed using the framework approach. Findings cover three main themes: partnership worries; fertility concerns; and views about emotional and practical support received. Partnership worries included concerns about having to undergo treatment without a partner to support them; the fear of rejection by potential partners; and feelings about the precious time lost in diagnosis and treatment. Fertility concerns included dilemmas about having children and feelings about the options of pursuing Assisted Reproductive Techniques. Views about the emotional and practical support received included the overall support received as well as perceptions about the attitudes of health professionals towards fertility issues. Findings indicate that single childless women with breast cancer face additional vulnerabilities and may benefit from tailored support from health care professionals and interventions specifically targeted at them. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.

PubMed

Ricciuti, Biagio; Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

2016-09-01

Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.

Parathyroid Hormone-Related Peptide (PTHrP) as a New Target for Metastatic Breast Cancer: Evaluation in Preclinical Models

DTIC Science & Technology

2016-10-01

in PTHrP-ablated and non-ablated animals. Using CRISPr technology, we are developing pre-clinical PTHrP-ablated human triple-negative breast cancer...3.2.2.1 KO of human TNBC cells by Clustered Regularly Interspaced Short Palindromic Repeats ( Crispr ): % COMPLETED: 90% OF TASK. (ON TIME). A unique... CRISPR sequence for PTHrP was chosen from pre-designed sites in the human genome using online tools (Sigma-Aldrich). The sites are designed to

Quality of Life among Immigrant Latina Breast Cancer Survivors: Realities of Culture and Enhancing Cancer Care

PubMed Central

Lopez-Class, Maria; Perret-Gentil, Monique; Kreling, Barbara; Caicedo, Larisa; Mandelblatt, Jeanne; Graves, Kristi D.

2012-01-01

Objectives Breast cancer is the most common cancer among Latinas. This study examined social, cultural, and health care system factors that impact quality of life and survivorship experiences of Latina immigrant breast cancer survivors. Design We interviewed Latina breast cancer survivors (n=19) and, based on the interview findings, conducted two focus groups (n=9). Research staff translated transcripts from Spanish into English. Two trained raters reviewed the content and identified themes. Thematic content analysis was used to categorize and organize data. Results Participants were largely mono-lingual in Spanish, predominantly from Central and South America and most (68%) had lived in the U.S. for 10 or more years. All women were diagnosed and treated in the U.S. and were an average of 3.1 years from diagnosis. Women’s survivorship experiences appeared to be shaped by cultural beliefs and experiences as immigrants such as secrecy/shame about a breast cancer diagnosis, feelings of isolation, importance of family support (familism), challenges with developing social relationships in the U.S. (less personalismo), and, for some, their partner’s difficulty with showing emotional support (machismo). Navigating the U.S. medical system and language barriers were additional challenges in participants’ health care interactions. Conclusion Latina breast cancer survivors adhere to certain cultural values and face unique issues as immigrants, potentially influencing overall quality of life and doctor-patient communication. Efforts to improve Latina immigrant breast cancer survivors’ quality of life could include increased assessment of psychosocial functioning and referral to social support services, culturally-sensitive navigation programs and consistent use of appropriately trained interpreters. PMID:21706194

Six low-penetrance SNPs for the estimation of breast cancer heritability: A family-based study in Caucasian Italian patients

PubMed Central

De Summa, Simona; Graziano, Francesca; Pilato, Brunella; Pinto, Rosamaria; Danza, Katia; Lacalamita, Rosanna; Serratì, Simona; Sambiasi, Domenico; Grassi, Mario; Tommasi, Stefania

2017-01-01

Breast cancer is a malignancy with a strong heritable component. Genetic counseling has been principally focused on families carrying high-penetrance breast cancer 1/2, early onset genes. Current modeling suggests that the majority of the unexplained fraction of familial risk is likely to be explained by a polygenic model. The aim of the present study was to estimate the heritability (h2) of breast cancer susceptibility through the analysis of 6 single nucleotide polymorphisms (SNPs), nuclear mitotic apparatus protein 1, cyclin D1, cytochrome C oxidase copper chaperone, fibroblast growth factor receptor 2, TOX high mobility group box family member 3 and solute carrier family 4 member 7. These 6 SNPs, previously identified by genome-wide association studies, were considered to evaluate the additive and common environmental components that contribute to the development of breast cancer in nuclear (pedigrees including only first degree relationships) and in extended families (with at most third degree relationships). A total of 22 extended pedigrees, subsequently split into 52 nuclear pedigrees were analyzed. An example of splitting process from extended to nuclear pedigree is shown in Fig. 1. Firstly, an underline latent continuous trait (Y*) using breast cancer status and information of 6 breast cancer-associated SNPs was calculated. This novel trait summarized the susceptibility of breast cancer in each individual. Secondly, the h2 of Y* was estimated using an additive polygenic-common environment-unique error model. h2 was evaluated in extended and immediate pedigrees, obtaining comparable results. h2 accounts for ~40% of the total phenotypic variance, indicating a fairly strong additive genetic effect of breast cancer susceptibility. The present study indicated the importance of the evaluation and consideration of these six SNPs, which can be used as instrumental variables in order to obtain improved genetic models that are useful for h2 analysis. PMID:28943953

Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

PubMed

Leon Guerrero, Rachael T; Novotny, Rachel; Wilkens, Lynne R; Chong, Marie; White, Kami K; Shvetsov, Yurii B; Buyum, Arielle; Badowski, Grazyna; Blas-Laguaña, Michelle

2017-10-01

Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to <20y, P for trend=0.01). Of the lifestyle factors -body mass index, waist circumference, physical activity, alcohol and betel-nut intake, and education - only waist circumference (OR=1.65; 95% CI 0.87-3.14 for the highest tertile group compared to the lowest, P for trend=0.04) was significantly associated with breast cancer risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

PubMed

Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

2018-05-28

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Breast care screening for underserved African American women: Community-based participatory approach.

PubMed

Davis, Cindy; Darby, Kathleen; Moore, Matthew; Cadet, Tamara; Brown, Gwendolynn

2017-01-01

Traditional health promotion models often do not take into account the importance of shared cultural backgrounds, beliefs, and experiences unique to underserved African American women when designing community-based cancer screening and prevention programs. Thus, the purpose of this study was the development, implementation, and evaluation of a community-based participatory research (CBPR) program designed to increase breast cancer screening awareness in an underserved African American population by providing culturally appropriate social support and information. The study includes 357 African American women who participated in the program and completed the 6-month follow-up questionnaire. The program consisted of a 45-minute play, using community members and storytelling to honor and incorporate five different cultural experiences (skits) with breast care and cancer. Overall, findings indicate that the educational intervention was effective. In addition, these findings are consistent with the literature that suggests that educational interventions that include knowledge to alleviate concerns, dispel myths, and create awareness can increase breast cancer screening participation rates. Furthermore, these findings confirm the importance of CBPR in health promotion activities in reducing health and cancer disparities.

Mujeres felices por ser saludables: a breast cancer risk reduction program for Latino women.

PubMed

Fitzgibbon, Marian L; Gapstur, Susan M; Knight, Sara J

2003-05-01

Breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality among Latino women. Several behavioral factors such as early detection and dietary practices could help decrease morbidity and mortality associated with breast cancer in this population. Unfortunately, there are few data regarding the efficacy of health-related interventions for young Latino women. Mujeres Felices por ser Saludables is a randomized intervention project designed to assess breast cancer risk reduction behavior among Latino women ages 20-40 years. The primary objectives of the project were to determine whether an 8-month integrated dietary/breast health intervention could lead to a greater reduction in dietary fat, increase in dietary fiber, increase in the frequency and proficiency of breast self examination (BSE), and reduction in anxiety related to BSE compared to controls. Herein we describe the overall design of the project and present baseline characteristics of the 256 randomized women. Our results suggest that the average daily intake of dietary fat (percentage of total energy) was slightly below 30% (percentage of total energy) among the women randomized. While over half of these women reported that they practice BSE, and few reported anxiety related to BSE, less than 27% of women were proficient in the recommended BSE technique. There are few data on the dietary and breast health behaviors of young low-acculturated Latino women. This study documents the feasibility of recruiting, randomizing, and obtaining both baseline dietary and breast health data on this unique and underserved population.

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

PubMed Central

Shafran, Yana; Zurgil, Naomi; Ravid-Hermesh, Orit; Sobolev, Maria; Afrimzon, Elena; Hakuk, Yaron; Shainberg, Asher; Deutsch, Mordechai

2017-01-01

Estrogen-induced apoptosis has become a successful treatment for postmenopausal metastatic, estrogen receptor-positive breast cancer. Nitric oxide involvement in the response to this endocrine treatment and its influence upon estrogen receptor-positive breast cancer progression is still unclear. Nitric oxide impact on the MCF7 breast cancer line, before and after estrogen-induced apoptosis, was investigated in 3D culture systems using unique live-cell imaging methodologies. Spheroids were established from MCF7 cells vulnerable to estrogen-induced apoptosis, before and after exposure to estrogen. Spheroids derived from estrogen-treated cells exhibited extensive apoptosis levels with downregulation of estrogen receptor expression, low proliferation rate and reduced metabolic activity, unlike spheroids derived from non-treated cells. In addition to basic phenotypic differences, these two cell cluster types are diverse in their reactions to exogenous nitric oxide. A dual effect of nitric oxide was observed in the breast cancer phenotype sensitive to estrogen-induced apoptosis. Nitric oxide, at the nanomolar level, induced cell proliferation, high metabolic activity, downregulation of estrogen receptor and enhanced collective invasion, contributing to a more aggressive phenotype. Following hormone supplementation, breast cancer 3D clusters were rescued from estrogen-induced apoptosis by these low nitric oxide-donor concentrations, since nitric oxide attenuates cell death levels, upregulates survivin expression and increases metabolic activity. Higher nitric oxide concentrations (100nM) inhibited cell growth, metabolism and promoted apoptosis. These results suggest that nitric oxide, in nanomolar concentrations, may inhibit estrogen-induced apoptosis, playing a major role in hormonal therapy. Inhibiting nitric oxide activity may benefit breast cancer patients and ultimately reduce tumor recurrence. PMID:29312577

Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?

PubMed

Oesterreich, Steffi

2003-11-01

Scaffold attachment factor B1 (SAFB1) and SAFB2 are large, multifunctional proteins that have been implicated in numerous cellular processes including chromatin organization, transcriptional regulation, RNA splicing, and stress response. While the two homologous proteins show high similarity, and functional domains are highly conserved, evidence suggests that they also have unique properties. For example, SAFB2 can be found in both the nucleus and cytoplasm, whereas SAFB1 seems to be mainly localized in the nucleus. In breast cancer cells, SAFBs function as estrogen receptor corepressors and growth inhibitors. SAFB protein expression is lost in approximately 20% of breast cancers. Interestingly, the two genes reside in close proximity, oriented head-to-head, on chromosome 19p13, a locus which is frequently lost in clinical breast cancer specimens. Furthermore, SAFB1 mutations have been identified in breast tumors that were not present in adjacent normal tissue. The possibility that SAFB1 and SAFB2 are novel breast tumor suppressor genes, and how they might function in this role, are discussed. Copyright 2003 Wiley-Liss, Inc.

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

PubMed

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

TGF-β1-Induced Epithelial–Mesenchymal Transition Promotes Monocyte/Macrophage Properties in Breast Cancer Cells

PubMed Central

Johansson, Joel; Tabor, Vedrana; Wikell, Anna; Jalkanen, Sirpa; Fuxe, Jonas

2015-01-01

Breast cancer progression toward metastatic disease is linked to re-activation of epithelial–mesenchymal transition (EMT), a latent developmental process. Breast cancer cells undergoing EMT lose epithelial characteristics and gain the capacity to invade the surrounding tissue and migrate away from the primary tumor. However, less is known about the possible role of EMT in providing cancer cells with properties that allow them to traffic to distant sites. Given the fact that pro-metastatic cancer cells share a unique capacity with immune cells to traffic in-and-out of blood and lymphatic vessels we hypothesized that tumor cells undergoing EMT may acquire properties of immune cells. To study this, we performed gene-profiling analysis of mouse mammary EpRas tumor cells that had been allowed to adopt an EMT program after long-term treatment with TGF-β1 for 2 weeks. As expected, EMT cells acquired traits of mesenchymal cell differentiation and migration. However, in addition, we found another cluster of induced genes, which was specifically enriched in monocyte-derived macrophages, mast cells, and myeloid dendritic cells, but less in other types of immune cells. Further studies revealed that this monocyte/macrophage gene cluster was enriched in human breast cancer cell lines displaying an EMT or a Basal B profile, and in human breast tumors with EMT and undifferentiated (ER−/PR−) characteristics. The results identify an EMT-induced monocyte/macrophage gene cluster, which may play a role in breast cancer cell dissemination and metastasis. PMID:25674539

Identification of shared and unique susceptibility pathways among cancers of the lung, breast, and prostate from genome-wide association studies and tissue-specific protein interactions

PubMed Central

Qian, David C.; Byun, Jinyoung; Han, Younghun; Greene, Casey S.; Field, John K.; Hung, Rayjean J.; Brhane, Yonathan; Mclaughlin, John R.; Fehringer, Gordon; Landi, Maria Teresa; Rosenberger, Albert; Bickeböller, Heike; Malhotra, Jyoti; Risch, Angela; Heinrich, Joachim; Hunter, David J.; Henderson, Brian E.; Haiman, Christopher A.; Schumacher, Fredrick R.; Eeles, Rosalind A.; Easton, Douglas F.; Seminara, Daniela; Amos, Christopher I.

2015-01-01

Results from genome-wide association studies (GWAS) have indicated that strong single-gene effects are the exception, not the rule, for most diseases. We assessed the joint effects of germline genetic variations through a pathway-based approach that considers the tissue-specific contexts of GWAS findings. From GWAS meta-analyses of lung cancer (12 160 cases/16 838 controls), breast cancer (15 748 cases/18 084 controls) and prostate cancer (14 160 cases/12 724 controls) in individuals of European ancestry, we determined the tissue-specific interaction networks of proteins expressed from genes that are likely to be affected by disease-associated variants. Reactome pathways exhibiting enrichment of proteins from each network were compared across the cancers. Our results show that pathways associated with all three cancers tend to be broad cellular processes required for growth and survival. Significant examples include the nerve growth factor (P = 7.86 × 10−33), epidermal growth factor (P = 1.18 × 10−31) and fibroblast growth factor (P = 2.47 × 10−31) signaling pathways. However, within these shared pathways, the genes that influence risk largely differ by cancer. Pathways found to be unique for a single cancer focus on more specific cellular functions, such as interleukin signaling in lung cancer (P = 1.69 × 10−15), apoptosis initiation by Bad in breast cancer (P = 3.14 × 10−9) and cellular responses to hypoxia in prostate cancer (P = 2.14 × 10−9). We present the largest comparative cross-cancer pathway analysis of GWAS to date. Our approach can also be applied to the study of inherited mechanisms underlying risk across multiple diseases in general. PMID:26483192

Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

PubMed

Locke, Warwick J; Clark, Susan J

2012-11-15

Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic phenomena that occur during the progression from normal breast to pre-malignancy. Therefore, the HMEC model system provides the unique opportunity to study the very earliest epigenomic aberrations occurring during breast carcinogenesis and can give insight into the sequence of epigenomic events that lead to breast malignancy. This review provides an overview of epigenomic research in breast cancer and discusses in detail the utility of the HMEC model system to discover early epigenomic changes involved in breast carcinogenesis.

Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis

PubMed Central

2012-01-01

Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic phenomena that occur during the progression from normal breast to pre-malignancy. Therefore, the HMEC model system provides the unique opportunity to study the very earliest epigenomic aberrations occurring during breast carcinogenesis and can give insight into the sequence of epigenomic events that lead to breast malignancy. This review provides an overview of epigenomic research in breast cancer and discusses in detail the utility of the HMEC model system to discover early epigenomic changes involved in breast carcinogenesis. PMID:23168266

Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report.

PubMed

Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

2015-01-01

At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Minority stress, psychosocial resources, and psychological distress among sexual minority breast cancer survivors.

PubMed

Kamen, Charles; Jabson, Jennifer M; Mustian, Karen M; Boehmer, Ulrike

2017-06-01

Few studies have examined unique factors predicting psychological distress among sexual minority (i.e., lesbian and bisexual) women postbreast cancer diagnosis. The present study assessed the association of minority stress and psychosocial resource factors with depression and anxiety symptoms among sexual minority breast cancer survivors. Two hundred one sexual minority women who had ductal carcinoma in situ or Stage I-IV breast cancer participated in this study through the Love/Avon Army of Women. Self-report questionnaires were used to assess demographic and clinical factors, minority stress factors (discrimination, minority identity development, outness), psychosocial resources (resilience, social support), and psychological distress (anxiety and depression). These factors were included in a structural equation model, testing psychosocial resources as mediators between minority stress and psychological distress. There were no significant differences noted between lesbian and bisexual women. The final structural equation model demonstrated acceptable fit across all sexual minority women, χ2 = 27.83, p > .05; confirmatory fit index = 0.97, root-mean-square error of approximation = 0.04, Tucker-Lewis index = 0.93. The model accounted for significant variance in psychological distress (56%). Examination of indirect effects confirmed that exposure to discrimination was associated with distress via association with resilience. Factors unique to sexual minority populations, such as minority stress, may be associated with higher rates of psychological distress among sexual minority breast cancer survivors. However, presence of psychosocial resources may mediate relationships with distress in this population; enhancement of resilience, in particular, could be an aim of psychological intervention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions

PubMed Central

Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

2011-01-01

Abstract Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies, as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3, PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. PMID:20132413

Improving outcomes from breast cancer in a low-income country: lessons from bangladesh.

PubMed

Story, H L; Love, R R; Salim, R; Roberto, A J; Krieger, J L; Ginsburg, O M

2012-01-01

Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high-income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh.

A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience.

PubMed

McKee, Megan J; Keith, Kevin; Deal, Allison M; Garrett, Amy L; Wheless, Amy A; Green, Rebecca L; Benbow, Julie M; Dees, E Claire; Carey, Lisa A; Ewend, Matthew G; Anders, Carey K; Zagar, Timothy M

2016-01-01

Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER2- breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER2+ breast cancer (p = .0037). Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. Patients with breast cancer brain metastases often require unique multidisciplinary care to meet the numerous and uncommon challenges associated with their conditions. Here, the development and characteristics of a clinic designed specifically to provide for the multidisciplinary needs of patients with breast cancer brain metastases are described. This clinic may serve as a model for other institutions interested in creating specialty clinics with similar objectives. ©AlphaMed Press.

Molecular characterization of breast cancer cell lines through multiple omic approaches.

PubMed

Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H

2017-06-05

Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated in common or unique ways. These two new kinase or "Kin-OMIC" analyses add another dimension of important data about these frequently used breast cancer cell lines. This will assist researchers in selecting the most appropriate cell lines to use for breast cancer studies and provide context for the interpretation of the emerging results.

InforMD: a new initiative to raise public awareness about breast density

PubMed Central

Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

2018-01-01

On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with a well-informed and updated website, has laid the groundwork for the InforMD alliance to reach a wide audience. PMID:29492101

InforMD: a new initiative to raise public awareness about breast density.

PubMed

Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

2018-01-01

On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with a well-informed and updated website, has laid the groundwork for the InforMD alliance to reach a wide audience.

Feasibility of a psychosocial and patient navigation intervention to improve access to treatment among underserved breast cancer patients.

PubMed

Madore, Shannon; Kilbourn, Kristin; Valverde, Patricia; Borrayo, Evelinn; Raich, Peter

2014-08-01

Medically underserved women with recently diagnosed breast cancer face a number of significant obstacles that impact the timeliness and quality of their care. The Breast CARES (Cancer Advocacy, Resources Education and Support) intervention combined patient navigation with telephone counseling to guide newly diagnosed breast cancer patients in overcoming treatment barriers. The study aimed to learn more about the types of barriers encountered by the participants. The study also sought to understand the relationship between patient-reported barriers and patient-reported psychosocial distress in underserved women recently diagnosed with breast cancer. Data were analyzed using a mixed-methods approach. Participants were assessed pre- and post-intervention. Psychosocial measures included cancer-related distress, depression, anxiety, social support, and quality of life. Case notes and responses to process evaluation questions were used to determine whether the CARES intervention adequately addressed the needs of the participants. The mean age of participants (N = 20) was 54 years (SD = 12.5), 40% were Hispanic, 70% were unemployed, 50% were uninsured, and 20% were mono-lingual in Spanish. Qualitative analysis revealed four categories of barriers: psychosocial, medical, logistical, and communication. Similarities and differences existed between the PN and TC regarding how barriers were addressed. Post-intervention psychosocial scores indicate a decrease in depression and cancer-related distress and an increase in social support. The participants reported that participation in the Breast CARES program helped them overcome financial barriers (73%), transportation problems (60%), and communication barriers with medical staff (73%). This study demonstrates the unique and complementary roles for PNs and TCs in overcoming barriers to treatment adherence faced by underserved breast cancer patients.

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

PubMed

Kimbung, Siker; Johansson, Ida; Danielsson, Anna; Veerla, Srinivas; Egyhazi Brage, Suzanne; Frostvik Stolt, Marianne; Skoog, Lambert; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Loman, Niklas; Malmström, Per-Olof; Söderberg, Martin; Walz, Thomas M; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2016-01-01

The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. ©2015 American Association for Cancer Research.

A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells.

PubMed

Hao, Sijie; Ha, Laura; Cheng, Gong; Wan, Yuan; Xia, Yiqiu; Sosnoski, Donna M; Mastro, Andrea M; Zheng, Si-Yang

2018-03-01

Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analytical Pipeline for Discovery and Verification of Glycoproteins from Plasma-Derived Extracellular Vesicles as Breast Cancer Biomarkers.

PubMed

Chen, I-Hsuan; Aguilar, Hillary Andaluz; Paez Paez, J Sebastian; Wu, Xiaofeng; Pan, Li; Wendt, Michael K; Iliuk, Anton B; Zhang, Ying; Tao, W Andy

2018-05-15

Glycoproteins comprise more than half of current FDA-approved protein cancer markers, but the development of new glycoproteins as disease biomarkers has been stagnant. Here we present a pipeline to develop glycoproteins from extracellular vesicles (EVs) through integrating quantitative glycoproteomics with a novel reverse phase glycoprotein array and then apply it to identify novel biomarkers for breast cancer. EV glycoproteomics show promise in circumventing the problems plaguing current serum/plasma glycoproteomics and allowed us to identify hundreds of glycoproteins that have not been identified in blood. We identified 1,453 unique glycopeptides representing 556 glycoproteins in EVs, among which 20 were verified significantly higher in individual breast cancer patients. We further applied a novel glyco-specific reverse phase protein array to quantify a subset of the candidates. Together, this study demonstrates the great potential of this integrated pipeline for biomarker discovery.

Fluorodeoxyglucose--positive internal mammary lymph node in breast cancer patients with silicone implants: is it always metastatic cancer?

PubMed

Soudack, Michalle; Yelin, Alon; Simansky, David; Ben-Nun, Alon

2013-07-01

Patients with breast cancer following mastectomy and silicone implant reconstruction may have enlarged internal mammary lymph nodes with pathological uptake on positron emission tomography with (18)F-fluorodeoxyglucose. This lymphadenopathy is usually considered as metastatic in nature, but has also been reported to be related to other conditions, including silicon migration. The purpose of this study was to determine the rate of metastatic disease in this unique group of patients. A retrospective comparative study of 12 female patients with breast cancer with silicone implants referred for biopsy due to isolated internal mammary lymph node fluorodeoxyglucose uptake on positron emission tomography. Five patients (41.6%) had histological findings related to silicone (n = 4) or non-specific inflammation (n = 1). The remaining 7 (58.3%) had histological evidence of cancer recurrence. There was no significant difference in the fluorodeoxyglucose-standardized uptake value between the two groups. Fluorodeoxyglucose-positive mammary lymph nodes in patients with breast cancer following silicone implant reconstruction may be due to metastatic deposits, non-specific inflammation or silicone migration. Clinical and imaging characteristics are insufficient in differentiating between these conditions. Biopsy is recommended prior to initiation of further treatment.

Bilateral breast keloids in an elderly woman associated with bilateral breast cancers and high concentration of serum tumor growth factor-β.

PubMed

Sakaguchi, Masanobu; Fukumoto, Takeshi; Fujishima, Fumiyoshi; Fukuda, Kaori; Kozaru, Takeshi; Ban, Masao; Oka, Masahiro

2017-11-01

We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution. © 2017 Japanese Dermatological Association.

Tradeoffs of Using Administrative Claims and Medical Records to Identify the Use of Personalized Medicine for Patients with Breast Cancer

PubMed Central

Liang, Su-Ying; Phillips, Kathryn A.; Wang, Grace; Keohane, Carol; Armstrong, Joanne; Morris, William M.; Haas, Jennifer S.

2012-01-01

Background Administrative claims and medical records are important data sources to examine healthcare utilization and outcomes. Little is known about identifying personalized medicine technologies in these sources. Objectives To describe agreement, sensitivity, and specificity of administrative claims compared to medical records for two pairs of targeted tests and treatments for breast cancer. Research Design Retrospective analysis of medical records linked to administrative claims from a large health plan. We examined whether agreement varied by factors that facilitate tracking in claims (coding and cost) and that enhance medical record completeness (records from multiple providers). Subjects Women (35 – 65 years) with incident breast cancer diagnosed in 2006–2007 (n=775). Measures Use of human epidermal growth factor receptor 2 (HER2) and gene expression profiling (GEP) testing, trastuzumab and adjuvant chemotherapy in claims and medical records. Results Agreement between claims and records was substantial for GEP, trastuzumab, and chemotherapy, and lowest for HER2 tests. GEP, an expensive test with unique billing codes, had higher agreement (91.6% vs. 75.2%), sensitivity (94.9% vs. 76.7%), and specificity (90.1% vs. 29.2%) than HER2, a test without unique billing codes. Trastuzumab, a treatment with unique billing codes, had slightly higher agreement (95.1% vs. 90%) and sensitivity (98.1% vs. 87.9%) than adjuvant chemotherapy. Conclusions Higher agreement and specificity were associated with services that had unique billing codes and high cost. Administrative claims may be sufficient for examining services with unique billing codes. Medical records provide better data for identifying tests lacking specific codes and for research requiring detailed clinical information. PMID:21422962

Day as a Pathologist: Utilization of Technology to Guide Students in Exploring Careers in Breast Cancer Pathology

ERIC Educational Resources Information Center

Adler, Jacob J.; Judd, Mariah V.; Bringman, Lauren R.; Wells, Clark D.; Marrs, Kathleen A.

2013-01-01

We developed an interactive laboratory that allows students to identify and grade tissue samples from human breast biopsies, using techniques similar to those used by actual pathologists. This unique lab develops a practical and intellectual understanding of basic tissue structures that make up living systems, utilizing technology to bring…

Noble Hybrid Nanostructures as Efficient Anti-Proliferative Platforms for Human Breast Cancer Cell.

PubMed

Tavangar, Amirhossein; Premnath, Priyatha; Tan, Bo; Venkatakrishnan, Krishnan

2016-04-27

Nanomaterials have proven to possess great potential in biomaterials research. Recently, they have suggested considerable promise in cancer diagnosis and therapy. Among others, silicon (Si) nanomaterials have been extensively employed for various biomedical applications; however, the utilization of Si for cancer therapy has been limited to nanoparticles, and its potential as anticancer substrates has not been fully explored. Noble nanoparticles have also received considerable attention owing to unique anticancer properties to improve the efficiency of biomaterials for numerous biological applications. Nevertheless, immobilization and control over delivery of the nanoparticles have been challenge. Here, we develop hybrid nanoplatforms to efficiently hamper breast cancer cell adhesion and proliferation. Platforms are synthesized by femtosecond laser processing of Si into multiphase nanostructures, followed by sputter-coating with gold (Au)/gold-palladium (Au-Pd) nanoparticles. The performance of the developed platforms was then examined by exploring the response of normal fibroblast and metastatic breast cancer cells. Our results from the quantitative and qualitative analyses show a dramatic decrease in the number of breast cancer cells on the hybrid platform compared to untreated substrates. Whereas, fibroblast cells form stable adhesion with stretched and elongated cytoskeleton and actin filaments. The hybrid platforms perform as dual-acting cytophobic/cytostatic stages where Si nanostructures depress breast cancer cell adhesion while immobilized Au/Au-Pd nanoparticles are gradually released to affect any surviving cell on the nanostructures. The nanoparticles are believed to be taken up by breast cancer cells via endocytosis, which subsequently alter the cell nucleus and may cause cell death. The findings suggest that the density of nanostructures and concentration of coated nanoparticles play critical roles on cytophobic/cytostatic properties of the platforms on human breast cancer cells while having no or even cytophilic effects on fibroblast cells. Because of the remarkable contrary responses of normal and cancer cells to the proposed platform, we envision that it will provide novel applications in cancer research.

MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells

PubMed Central

2013-01-01

Background A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells (BT-ICs) may open the road for novel therapeutic strategies. As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions. Results We found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression. Conclusions miR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs. PMID:23445407

Can breast cancer patients use soyafoods to help reduce risk of CHD?

PubMed

Messina, Mark; Messina, Virginia; Jenkins, David J A

2012-09-01

Over the past 20 years, the popularity of soyafoods has increased in part because of research suggesting that these foods convey health benefits independent of their nutrient content. For example, in 1999, the US Food and Drug Administration approved a health-claim for soyafoods and CHD based on the hypocholesterolaemic effects of soya protein. However, soyafoods have become controversial in recent years because of concerns that their uniquely rich phyto-oestrogen (isoflavone) content may cause untoward effects in some individuals. Most notable in this regard is the concern that soyafoods are contraindicated for breast cancer patients and women at high risk of developing this disease. Furthermore, the hypocholesterolaemic effects of soya protein have been challenged. However, the results of recently published meta-analyses indicate that soya protein directly lowers circulating LDL-cholesterol levels by approximately 4 %. There is also intriguing evidence that soyafoods reduce CHD risk independent of their effects on lipid levels. In regard to the breast cancer controversy, recently published clinical and epidemiological data do not support observations in rodents that soyabean isoflavones increase breast cancer risk. In postmenopausal women, isoflavone exposure does not adversely affect breast tissue density or breast cell proliferation. Furthermore, both US and Chinese prospective epidemiological studies show that post-diagnosis soya consumption is associated with an improved prognosis. Therefore, soyafoods should be considered by women as healthy foods to include in diets aimed at reducing the risk of CHD regardless of their breast cancer status.

Content analysis of Australian direct-to-consumer websites for emerging breast cancer imaging devices.

PubMed

Vreugdenburg, Thomas D; Laurence, Caroline O; Willis, Cameron D; Mundy, Linda; Hiller, Janet E

2014-09-01

To describe the nature and frequency of information presented on direct-to-consumer websites for emerging breast cancer imaging devices. Content analysis of Australian website advertisements from 2 March 2011 to 30 March 2012, for three emerging breast cancer imaging devices: digital infrared thermal imaging, electrical impedance scanning and electronic palpation imaging. Type of imaging offered, device safety, device performance, application of device, target population, supporting evidence and comparator tests. Thirty-nine unique Australian websites promoting a direct-to-consumer breast imaging device were identified. Despite a lack of supporting evidence, 22 websites advertised devices for diagnosis, 20 advertised devices for screening, 13 advertised devices for prevention and 13 advertised devices for identifying breast cancer risk factors. Similarly, advertised ranges of diagnostic sensitivity (78%-99%) and specificity (44%-91%) were relatively high compared with published literature. Direct comparisons with conventional screening tools that favoured the new device were highly prominent (31 websites), and one-third of websites (12) explicitly promoted their device as a suitable alternative. Australian websites for emerging breast imaging devices, which are also available internationally, promote the use of such devices as safe and effective solutions for breast cancer screening and diagnosis in a range of target populations. Many of these claims are not supported by peer-reviewed evidence, raising questions about the manner in which these devices and their advertising material are regulated, particularly when they are promoted as direct alternatives to established screening interventions.

Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy.

PubMed

Wan, Guoyun; Chen, Bowei; Li, Ling; Wang, Dan; Shi, Shurui; Zhang, Tao; Wang, Yue; Zhang, Lianyun; Wang, Yinsong

2018-02-01

Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients.

PubMed

Tsunashima, Ryo; Naoi, Yasuto; Shimazu, Kenzo; Kagara, Naofumi; Shimoda, Masashi; Tanei, Tomonori; Miyake, Tomohiro; Kim, Seung Jin; Noguchi, Shinzaburo

2018-05-04

Prediction models for late (> 5 years) recurrence in ER-positive breast cancer need to be developed for the accurate selection of patients for extended hormonal therapy. We attempted to develop such a prediction model focusing on the differences in gene expression between breast cancers with early and late recurrence. For the training set, 779 ER-positive breast cancers treated with tamoxifen alone for 5 years were selected from the databases (GSE6532, GSE12093, GSE17705, and GSE26971). For the validation set, 221 ER-positive breast cancers treated with adjuvant hormonal therapy for 5 years with or without chemotherapy at our hospital were included. Gene expression was assayed by DNA microarray analysis (Affymetrix U133 plus 2.0). With the 42 genes differentially expressed in early and late recurrence breast cancers in the training set, a prediction model (42GC) for late recurrence was constructed. The patients classified by 42GC into the late recurrence-like group showed a significantly (P = 0.006) higher late recurrence rate as expected but a significantly (P = 1.62 × E-13) lower rate for early recurrence than non-late recurrence-like group. These observations were confirmed for the validation set, i.e., P = 0.020 for late recurrence and P = 5.70 × E-5 for early recurrence. We developed a unique prediction model (42GC) for late recurrence by focusing on the biological differences between breast cancers with early and late recurrence. Interestingly, patients in the late recurrence-like group by 42GC were at low risk for early recurrence.

Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.

PubMed

Gomez-Miragaya, Jorge; González-Suárez, Eva

2017-01-01

Taxanes are mainstay treatment of triple negative breast cancer (TNBC) patients but resistance often develops. Using TNBC patient-derived orthoxenografts (PDX) we have recently discovered that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands in tumors that have acquired resistance. Importantly, sensitivity to taxanes is recovered after long-term drug interruption. The characterization of this chemoresistant CD49f+ cells provides a unique opportunity to identify novel targets for the treatment of chemoresistant TNBC.

Identification of 2,4-dihydroxy-5-pyrimidinyl imidothiocarbomate as a novel inhibitor to Y box binding protein-1 (YB-1) and its therapeutic actions against breast cancer.

PubMed

Gunasekaran, Vinoth Prasanna; Nishi, Kumari; Sivakumar, Dakshinamurthy; Sivaraman, Thirunavukkarasu; Mathan, Ganeshan

2018-04-30

In spite of advances in breast cancer treatment and early diagnosis, drug toxicity, cancer relapse, multidrug resistance and metastasis are the major impediment to the developments of efficient drugs. However, unique druggable targets of cancer cells distinct from the normal cells provide new rationale in cancer treatment. Previous reports clearly emphasize the differential expression and localization of Y box binding protein-1 (YB-1) between normal breast tissues and different stages of breast cancer. Y box binding protein-1 is DNA as well as RNA binding protein involved in transcription and translation regulation of various proteins involved in cancer progression, apoptosis, cell cycle, epithelial to mesenchymal transition (EMT) and drug resistance. Particularly, during doxorubicin (DOX) treatment and cancer relapse conditions, YB-1 expression was very high in breast cancer tissues and localized in to nucleus which further favours DOX efflux and metastasis. Moreover, siRNA mediated silencing of YB-1 reduces breast cancer progression and metastasis. In this rationale, using an array of computational methods, 2,4-dihydroxy-5-pyrimidinyl imidothiocarbomate (DPI) has been screened out as a drug-likeness antagonist to the YB-1for cancer treatment. In this study, we determined that DPI was toxic to breast cancer cell lines as individual drug as well as in combination with DOX. Moreover, immunofluorescence and confocal studies showed that DPI decreases DOX induced YB-1 nuclear translocation and increases DOX accumulation in breast cancer cell line. A G1/G0 phase cell cycle arrest and apoptosis was also induced by DPI. Moreover, DPI modulated YB-1 downstream targets such as p53, caspase-3, CDK-1 which are involved in cell cycle progression and apoptosis. Further, metastatic functional analysis revealed that DPI inhibits cell adhesion, migration, invasion in aggressive metastatic cell line and inhibits angiogenesis in chick embryonic chorioallantoic membrane (CAM) model. Meanwhile, DPI alters the expression of YB-1 downstream targets which are involved in metastasis such as VEGFR, caveolin, E-cadherin, cytokeratins, desmin and vimentin in MDA-MB-231 xenograft in chick embryonic CAM membrane. The results clearly demonstrated that DPI inhibited YB-1 nuclear translocation, thereby exhibited anti-apoptotic, anti-proliferative and anti-metastatic activities and increases the therapeutic potential of commercial breast cancer drug doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

Calibrating the imaging and therapy performance of magneto-fluorescent gold nanoshells for breast cancer

NASA Astrophysics Data System (ADS)

Dowell, Adam; Chen, Wenxue; Biswal, Nrusingh; Ayala-Orozco, Ciceron; Giuliano, Mario; Schiff, Rachel; Halas, Naomi J.; Joshi, Amit

2012-03-01

Gold nanoshells with NIR plasmon resonance can be modified to simultaneously enhance conjugated NIR fluorescence dyes and T2 contrast of embedded iron-oxide nanoparticles, and molecularly targeted to breast and other cancers. We calibrated the theranostic performance of magneto-fluorescent nanoshells, and contrasted the performance of molecularly targeted and untargeted nanoshells for breast cancer therapy, employing MCF-7L and their HER2 overexpressing derivative MCF-7/HER2-18 breast cancer cells as in vitro model systems. Silica core gold nanoshells with plasmon resonance on ~810 nm were doped with NIR dye ICG and ~10 nm iron-oxide nanoparticles in a ~20 nm epilayer of silica. A subset of nanoshells was conjugated to antibodies targeting HER2. Cell viability with varying laser power levels in presence and absence of bare and HER2-targeted nanoshells was assessed by calcein and propidium iodide staining. For MCF-7L cells, increasing power resulted in increased cell death (F=5.63, p=0.0018), and bare nanoshells caused more cell death than HER2-targeted nanoshells or laser treatment alone (F=30.13, p<0.001). For MCF-7/HER2-18 cells, death was greater with HER2-targeted nanoshells and was independent of laser power. This study demonstrates the capability of magneto-fluorescent nanocomplexes for imaging and therapy of breast cancer cells, and the advantages of targeting receptors unique to cancer cells.

Lessons learned in the trenches: facilitating exercise adherence among breast cancer survivors in a group setting.

PubMed

Rogers, Laura Q; Vicari, Sandy; Courneya, Kerry S

2010-01-01

Improving effectiveness of group exercise counseling for breast cancer survivors is needed. The objective of this study was to describe clinical observations, with research and translation implications, derived during group exercise counseling for breast cancer survivors. While implementing group session components of an effective social cognitive theory-based exercise intervention, observations were made through verbal discussion with study staff, review of participant feedback, and prospective journaling by the group facilitator. The intervention has been implemented 11 times (ie, 63 survivors; 66 group sessions). Thematic consistency, application to intervention goals and design, and implications were reconciled between 2 investigators. Breast cancer diagnosis was a strong source of commonality among group participants. Participant age, time since diagnosis, and expectation for group sessions (eg, group support vs health education) hindered group commonality. Barriers unique to the breast cancer experience were infrequent, but people-pleasing behavior was often identified as a barrier to adherence. Feeling at risk for cancer recurrence was a major concern. Some participants required referral for mental health evaluation for preexisting conditions (eg, depression). Although participants easily understood time management, application of other behavioral modification techniques was more difficult. A breast cancer diagnosis alone is not sufficient for commonality among group members. Teaching time management and positive reframing is essential. Protocols for appropriate mental health referrals are needed. Our observations will assist group facilitators in enhancing group dynamics and addressing obstacles hindering counseling effectiveness. Moreover, our results suggest hypotheses related to enhancing behavior change in a group setting worthy of future study.

TRPM7 controls mesenchymal features of breast cancer cells by tensional regulation of SOX4.

PubMed

Kuipers, Arthur J; Middelbeek, Jeroen; Vrenken, Kirsten; Pérez-González, Carlos; Poelmans, Geert; Klarenbeek, Jeffrey; Jalink, Kees; Trepat, Xavier; van Leeuwen, Frank N

2018-07-01

Mechanically induced signaling pathways are important drivers of tumor progression. However, if and how mechanical signals affect metastasis or therapy response remains poorly understood. We previously found that the channel-kinase TRPM7, a regulator of cellular tension implicated in mechano-sensory processes, is required for breast cancer metastasis in vitro and in vivo. Here, we show that TRPM7 contributes to maintaining a mesenchymal phenotype in breast cancer cells by tensional regulation of the EMT transcription factor SOX4. The functional consequences of SOX4 knockdown closely mirror those produced by TRPM7 knockdown. By traction force measurements, we demonstrate that TRPM7 reduces cytoskeletal tension through inhibition of myosin II activity. Moreover, we show that SOX4 expression and downstream mesenchymal markers are inversely regulated by cytoskeletal tension and matrix rigidity. Overall, our results identify SOX4 as a transcription factor that is uniquely sensitive to cellular tension and indicate that TRPM7 may contribute to breast cancer progression by tensional regulation of SOX4. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.

PubMed

Kwong, Ava; Shin, Vivian Y; Ho, John C W; Kang, Eunyoung; Nakamura, Seigo; Teo, Soo-Hwang; Lee, Ann S G; Sng, Jen-Hwei; Ginsburg, Ophira M; Kurian, Allison W; Weitzel, Jeffrey N; Siu, Man-Ting; Law, Fian B F; Chan, Tsun-Leung; Narod, Steven A; Ford, James M; Ma, Edmond S K; Kim, Sung-Won

2016-01-01

Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Improving Outcomes from Breast Cancer in a Low-Income Country: Lessons from Bangladesh

PubMed Central

Story, H. L.; Love, R. R.; Salim, R.; Roberto, A. J.; Krieger, J. L.; Ginsburg, O. M.

2012-01-01

Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high-income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh. PMID:22295245

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

DTIC Science & Technology

2004-08-01

established MTCIL tumor rolls retain this unique biologic feature. -ll suspeniionsw from sth moat vsital porn MTP ntutur arnd injected we inoutlated...rather than linear or continuous process. This biologic growth pattern is not unique nor unprecedented. Growth studies in children using serial height

Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer.

PubMed

Aponte-López, Angélica; Fuentes-Pananá, Ezequiel M; Cortes-Muñoz, Daniel; Muñoz-Cruz, Samira

2018-01-01

Mast cells are unique tissue-resident immune cells that secrete a diverse array of biologically active compounds that can stimulate, modulate, or suppress the immune response. Although mounting evidence supports that mast cells are consistently infiltrating tumors, their role as either a driving or an opposite force for cancer progression is still controversial. Particularly, in breast cancer, their function is still under discussion. While some studies have shown a protective role, recent evidence indicates that mast cells enhance blood and lymphatic vessel formation. Interestingly, one of the most important components of the mast cell cargo, the serine protease tryptase, is a potent angiogenic factor, and elevated serum tryptase levels correlate with bad prognosis in breast cancer patients. Likewise, histamine is known to induce tumor cell proliferation and tumor growth. In agreement, mast cell depletion reduces the size of mammary tumors and metastasis in murine models that spontaneously develop breast cancer. In this review, we will discuss the evidence supporting protumoral and antitumoral roles of mast cells, emphasizing recent findings placing mast cells as important drivers of tumor progression, as well as the potential use of these cells or their mediators as therapeutic targets.

Emotional suppression and depressive symptoms in women newly diagnosed with early breast cancer.

PubMed

Li, Lingyan; Yang, Yanjie; He, Jincai; Yi, Jinyao; Wang, Yuping; Zhang, Jinqiang; Zhu, Xiongzhao

2015-10-24

Patients with breast cancer usually present varying levels of depressive symptoms. Emotional suppression, as a coping style, refers to an individual's ability to consciously control expression of negative emotions. Thus, emotional suppression is an important psychological factor related to depressive symptoms in patients with breast cancer. It has long been considered that compared to European and American women, Chinese women are more likely to ascribe to norms of negative emotion control for smooth social interaction. However, there is paucity of research focusing on emotional suppression among Chinese women with breast cancer. Thus the aims of the current study were (1) to investigate the incidence of depressive symptoms in women newly diagnosed with early breast cancer in Mainland China, and (2) to examine the relationships between emotional suppression and depressive symptoms in these patients. The Center for Epidemiological Studies Depression Scale (CES-D), the Beck Anxiety Inventory (BAI) and the Chinese version of the Courtauld Emotional Control Scale (CECS) were used to assess the level of depressive symptoms, anxiety symptoms and emotional suppression respectively in 247 women with early breast cancer and 362 healthy women. Analyses of variance were conducted to investigate group differences on depressive symptoms and emotional suppression. Bivariate correlations and Hierarchical regression analyses were performed to examine the effect of emotional suppression on depressive symptoms in participants after controlling the impact of group membership and anxiety level. (1) The incidence rates of clinical and severe depressive symptoms in patients were 36.4 and 36.0 % respectively. (2) Patients scored significantly higher than healthy women on CECS. (3) The scores on CECS were significantly associated with the total CES-D scores in all participants; Anger suppression significantly predicted the total CES-D scores. The majority of women newly diagnosed with early breast cancer reported clinical or severe depressive symptoms. As well, these patients presented a controlled emotion coping style. Emotional suppression was associated with the level of depressive symptoms in women newly diagnosed with breast cancer. Anger suppression might play a unique role in the depressive symptoms among women newly diagnosed with breast cancer.

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

PubMed Central

Feng, Weiguo; Gentles, Andrew; Nair, Ramesh V.; Huang, Min; Lin, Yuan; Lee, Cleo Y.; Cai, Shang; Scheeren, Ferenc A.; Kuo, Angera H.; Diehn, Maximilian

2014-01-01

Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about heterogeneity of metabolic properties cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, play a critical role in promoting the pro-glycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminates TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a promising strategy for targeting these cells. PMID:24497069

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

PubMed Central

Ziegler, Yvonne S.; Moresco, James J.; Tu, Patricia G.; Yates, John R.; Nardulli, Ann M.

2014-01-01

The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease. PMID:25029196

Communication strategies to reduce cancer disparities: Insights from African-American mother-daughter dyads.

PubMed

Mosavel, Maghboeba; Wilson Genderson, Maureen; Ports, Katie A; Carlyle, Kellie E

2015-12-01

Mothers and daughters share a powerful and unique bond, which has potential for the dissemination of information on a variety of women's health issues, including the primary and secondary prevention of breast and cervical cancer. This study presents formative research from a long-term project examining the potential of mother-daughter communication in promoting cancer screening among African American women. Thirty-two mother-daughter pairs (N = 64) completed orally administered surveys regarding their cancer knowledge, beliefs and attitudes, and barriers to care. This study compares the attitudes and beliefs of low-income, urban, African American mothers and their adolescent daughters regarding cervical and breast cancer screening. Both mothers and daughters had fairly high levels of knowledge about breast and cervical cancer. In addition, there was a high concordance rate between mothers' and daughters' responses, suggesting a potential sharing of health knowledge between mother and daughter. These results have implications for selecting communication strategies to reduce health disparities, and support that the mother-daughter dyad could be a viable unit to disseminate targeted screening information. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Dispositional and Situational Avoidance and Approach as Predictors of Physical Symptom Bother Following Breast Cancer Diagnosis

PubMed Central

Bauer, Margaret R.; Harris, Lauren N.; Wiley, Joshua F.; Crespi, Catherine M.; Krull, Jennifer L.; Weihs, Karen L.; Stanton, Annette L.

2016-01-01

Background Few studies examine whether dispositional approach and avoidance coping and stressor-specific coping strategies differentially predict physical adjustment to cancer-related stress. Purpose This study examines dispositional and situational avoidance and approach coping as unique predictors of the bother women experience from physical symptoms after breast cancer treatment, as well as whether situational coping mediates the prediction of bother from physical symptoms by dispositional coping. Method Breast cancer patients (N=460) diagnosed within the past 3 months completed self-report measures of dispositional coping at study entry and of situational coping and bother from physical symptoms every 6 weeks through 6 months. Results In multilevel structural equation modeling analyses, both dispositional and situational avoidance predict greater symptom bother. Dispositional, but not situational, approach predicts less symptom bother. Supporting mediation models, dispositional avoidance predicts more symptom bother indirectly through greater situational avoidance. Dispositional approach predicts less symptom bother through less situational avoidance. Conclusion Psychosocial interventions to reduce cancer-related avoidance coping are warranted for cancer survivors who are high in dispositional avoidance and/or low in dispositional approach. PMID:26769023

Dispositional and Situational Avoidance and Approach as Predictors of Physical Symptom Bother Following Breast Cancer Diagnosis.

PubMed

Bauer, Margaret R; Harris, Lauren N; Wiley, Joshua F; Crespi, Catherine M; Krull, Jennifer L; Weihs, Karen L; Stanton, Annette L

2016-06-01

Few studies examine whether dispositional approach and avoidance coping and stressor-specific coping strategies differentially predict physical adjustment to cancer-related stress. This study examines dispositional and situational avoidance and approach coping as unique predictors of the bother women experience from physical symptoms after breast cancer treatment, as well as whether situational coping mediates the prediction of bother from physical symptoms by dispositional coping. Breast cancer patients (N = 460) diagnosed within the past 3 months completed self-report measures of dispositional coping at study entry and of situational coping and bother from physical symptoms every 6 weeks through 6 months. In multilevel structural equation modeling analyses, both dispositional and situational avoidance predict greater symptom bother. Dispositional, but not situational, approach predicts less symptom bother. Supporting mediation models, dispositional avoidance predicts more symptom bother indirectly through greater situational avoidance. Dispositional approach predicts less symptom bother through less situational avoidance. Psychosocial interventions to reduce cancer-related avoidance coping are warranted for cancer survivors who are high in dispositional avoidance and/or low in dispositional approach.

Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.

PubMed

Shah, Neal; Mohammad, Afroz S; Saralkar, Pushkar; Sprowls, Samuel A; Vickers, Schuyler D; John, Devin; Tallman, Rachel M; Lucke-Wold, Brandon P; Jarrell, Katherine E; Pinti, Mark; Nolan, Richard L; Lockman, Paul R

2018-03-28

In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2 + BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM. Copyright © 2018 Elsevier Ltd. All rights reserved.

CMS: A Web-Based System for Visualization and Analysis of Genome-Wide Methylation Data of Human Cancers

PubMed Central

Huang, Yi-Wen; Roa, Juan C.; Goodfellow, Paul J.; Kizer, E. Lynette; Huang, Tim H. M.; Chen, Yidong

2013-01-01

Background DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Methodology/Principal Findings Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. Conclusions/Significance CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/. PMID:23630576

CMS: a web-based system for visualization and analysis of genome-wide methylation data of human cancers.

PubMed

Gu, Fei; Doderer, Mark S; Huang, Yi-Wen; Roa, Juan C; Goodfellow, Paul J; Kizer, E Lynette; Huang, Tim H M; Chen, Yidong

2013-01-01

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/.

Breast imaging technology: Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects - applications to breast cancer

PubMed Central

Berger, Frank; Sam Gambhir, Sanjiv

2001-01-01

A variety of imaging technologies is being investigated as tools for studying gene expression in living subjects. Two technologies that use radiolabeled isotopes are single photon emission computed tomography (SPECT) and positron emission tomography (PET). A relatively high sensitivity, a full quantitative tomographic capability, and the ability to extend small animal imaging assays directly into human applications characterize radionuclide approaches. Various radiolabeled probes (tracers) can be synthesized to target specific molecules present in breast cancer cells. These include antibodies or ligands to target cell surface receptors, substrates for intracellular enzymes, antisense oligodeoxynucleotide probes for targeting mRNA, probes for targeting intracellular receptors, and probes for genes transferred into the cell. We briefly discuss each of these imaging approaches and focus in detail on imaging reporter genes. In a PET reporter gene system for in vivo reporter gene imaging, the protein products of the reporter genes sequester positron emitting reporter probes. PET subsequently measures the PET reporter gene dependent sequestration of the PET reporter probe in living animals. We describe and review reporter gene approaches using the herpes simplex type 1 virus thymidine kinase and the dopamine type 2 receptor genes. Application of the reporter gene approach to animal models for breast cancer is discussed. Prospects for future applications of the transgene imaging technology in human gene therapy are also discussed. Both SPECT and PET provide unique opportunities to study animal models of breast cancer with direct application to human imaging. Continued development of new technology, probes and assays should help in the better understanding of basic breast cancer biology and in the improved management of breast cancer patients. PMID:11250742

SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs.

PubMed

Blyth, Karen; Carter, Phil; Morrissey, Bethny; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

2016-04-01

Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating to the original projects. Despite being developed at considerable cost, this material is an invisible and hence an underutilised resource, which often ends up being discarded. Within the breast cancer research community there is both a need and desire to make this valuable material available for researchers. Lack of a coordinated system for visualisation and localisation of this has prevented progress. To fulfil this unmet need, we have developed a novel initiative called Sharing Experimental Animal Resources: Coordinating Holdings-Breast (SEARCHBreast) which facilitates sharing of archival tissue between researchers on a collaborative basis and, de facto will reduce overall usage of animal models in breast cancer research. A secure searchable database has been developed where researchers can find, share, or upload materials related to animal models of breast cancer, including genetic and transplant models. SEARCHBreast is a virtual compendium where the physical material remains with the original laboratory. A bioanalysis pipeline is being developed for the analysis of transcriptomics data associated with mouse models, allowing comparative study with human and cell line data. Additionally, SEARCHBreast is committed to promoting the use of humanised breast tissue models as replacement alternatives to animals. Access to this unique resource is freely available to all academic researchers following registration at https://searchbreast.org.

A Metabolomics Study of BPTES Altered Metabolism in Human Breast Cancer Cell Lines.

PubMed

Nagana Gowda, G A; Barding, Gregory A; Dai, Jin; Gu, Haiwei; Margineantu, Daciana H; Hockenbery, David M; Raftery, Daniel

2018-01-01

The Warburg effect is a well-known phenomenon in cancer, but the glutamine addiction in which cancer cells utilize glutamine as an alternative source of energy is less well known. Recent efforts have focused on preventing cancer cell proliferation associated with glutamine addiction by targeting glutaminase using the inhibitor BPTES (bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide). In the current study, an investigation of the BPTES induced changes in metabolism was made in two human breast cancer cell lines, MCF7 (an estrogen receptor dependent cell line) and MDA-MB231 (a triple negative cell line), relative to the non-cancerous cell line, MCF10A. NMR spectroscopy combined with a recently established smart-isotope tagging approach enabled quantitative analysis of 41 unique metabolites representing numerous metabolite classes including carbohydrates, amino acids, carboxylic acids and nucleotides. BPTES induced metabolism changes in the cancer cell lines were especially pronounced under hypoxic conditions with up to 1/3 of the metabolites altered significantly ( p < 0.05) relative to untreated cells. The BPTES induced changes were more pronounced for MCF7 cells, with 14 metabolites altered significantly ( p < 0.05) compared to seven for MDA-MB231. Analyses of the results indicate that BPTES affected numerous metabolic pathways including glycolysis, TCA cycle, nucleotide and amino acid metabolism in cancer. The distinct metabolic responses to BPTES treatment determined in the two breast cancer cell lines offer valuable metabolic information for the exploration of the therapeutic responses to breast cancer.

Breast cancer margin delineation with fluorescence lifetime imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Phipps, Jennifer E.; Gorpas, Dimitris; Darrow, Morgan; Unger, Jakob; Bold, Richard; Marcu, Laura

2017-02-01

The current standard of care for early stages of breast cancer is breast-conserving surgery (BCS). BCS involves a lumpectomy procedure, during which the tumor is removed with a rim of normal tissue-if cancer cells found in that rim of tissue, it is called a positive margin and means part of the tumor remains in the breast. Currently there is no method to determine if cancer cells exist at the margins of lumpectomy specimens aside from time-intensive histology methods that result in reoperations in up to 38% of cases. We used fluorescence lifetime imaging (FLIm) to measure time-resolved autofluorescence from N=13 ex vivo human breast cancer specimens (N=10 patients undergoing lumpectomy or mastectomy) and compared our results to histology. Tumor (both invasive and ductal carcinoma in situ), fibrous tissue, fat and fat necrosis have unique fluorescence signatures. For instance, between 500-580 nm, fluorescence lifetime of tumor was shortest (4.7 +/- 0.4 ns) compared to fibrous tissue (5.5 +/- 0.7 ns) and fat (7.0 +/- 0.1 ns), P<0.05 (ANOVA). These differences are due to the biochemical properties of lipid, nicotineamide adenine dinucleotide (NADH) and collagen fibers in the fat, tumor and fibrous tissue, respectively. Additionally, the FLIm data is augmented to video of the breast tissue with image processing algorithms that track a blue (450 nm) aiming beam used in parallel with the 355 nm excitation beam. This allows for accurate histologic co-registration and in the future will allow for three-dimensional lumpectomy surfaces to be imaged for cancer margin delineation.

Proteomic Analysis Reveals Aberrant O-GlcNAcylation of Extracellular Proteins from Breast Cancer Cell Secretion.

PubMed

Netsirisawan, Pukkavadee; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Svasti, Jisnuson; Champattanachai, Voraratt

2015-01-01

O-GlcNAcylation is a unique intracellular protein modification; however, few extracellular O-GlcNAc-modified proteins have been discovered. We have previously demonstrated that many cellular proteins were aberrant in O-GlcNAcylation in breast cancer tissues. In the present study, therefore, we investigated whether O-GlcNAc-modified proteins were abnormally secreted from breast cancer cells. Intracellular and extracellular proteins were prepared from cell lysates of breast cancer cells (MCF-7 and MDA-MB-231) and normal breast cells (HMEC) and from their serum-free media (SFM), respectively. O-GlcNAcylation level was examined by immunoblotting. O-GlcNAc-Modified proteins were identified using two-dimensional gel electrophoresis and Liquid Chromatography-tandem Mass Spectrometry. O-GlcNAcylation level was significantly increased in the extracellular compartment of both types of cancer cells compared to normal cells. Interestingly, O-GlcNAc patterns differed between intracellular and extracellular proteins. Proteomic analysis revealed that many O-GlcNAc spots in MCF-7 secretions were abnormally increased in comparison to those in HMEC secretions. Among these, transitional endoplasmic reticulum ATPase (TER ATPase) and heat-shock 70 kDa (HSP70) were confirmed to be O-GlcNAc-modified. The levels of O-GlcNAc-HSP70 and O-GlcNAc-TER ATPase were higher in SFM from MCF-7 cells than in that from HMEC. O-GlcNAcomic study of the extracellular compartments reveals aberrant O-GlcNAc-secreted proteins, which may be of interest as potential biomarkers in breast cancer. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data.

PubMed

Zhang, Hongwei; Zhu, Wei; Biskup, Ewelina; Yang, Weige; Yang, Ziang; Wang, Hong; Qiu, Xiaochun; Zhang, Chengjiao; Hu, Guangxia; Hu, Guangfu

2018-06-01

The aim was to systematically extrapolate the occurrence, risk factors, prognostic characteristics, management and outcome of bone metastases (BM) and skeletal related events (SREs) of breast cancer survivors in the real world clinical setting. A systematic literature search of PubMed, Web of Science, EMBASE OvidSP and EBSCO Academic Search Complete was conducted. Published prospective and retrospective papers investigating BM and SREs in breast cancer patients in non-trial settings were identified and systematically reviewed. Twenty-four studies met the inclusion criteria. Incidences of BM based on new diagnosis, length of BM-free interval (BMFI) and number and sites of BM were detected by 17 of 24 studies. Seven studies included in the review were subjected to analyses of risk factors for BM. Developments of SREs regarding the occurrence ratio of total and specific SREs, SERs-free interval (SREFI) and the first-line therapy for SREs were observed in 16 of 24 studies. Out of 5 studies, we extracted uni- and multivariate analysis of risk factor for SREs and out of 16 studies - predictors for survival in breast cancer patients with BM. BM and SREs are common problems in non-trial breast cancer populations. Patient demographics, clinical stage, tumor pathological type, molecular receptors status are significantly risk factors for incidence of BM, SREs and the survival. The unique characteristics of BM and SREs in breast cancer patients should be taken into account in future randomized controlled trials, as to optimize individual treatment options and assure a maximally long good quality of life.

Numerical analysis for characterization of the gold nanorod mediated-plasmonic heating with temporary NIR laser radiation for superficial breast cancer therapy

NASA Astrophysics Data System (ADS)

Bae, Ji Yong; Nam, Ki-Hwan; Jeong, Chan Bae; Kim, Geon-hee; Chang, Ki Soo

2016-09-01

Over the last decade, plasmonic photothermal therapy (PPTT) has received significant attention as the new therapeutic strategy for the cancer therapy due to unique characteristics of the gold-nanoparticles. The characterization of the spatiotemporal heating potential for the gold nanorods (GNR) through mimicking PPTT process on the various conditions can help more quantitative approaches to treatment planning. The purpose of this study was to clearly understand the optical-thermal interactions between the laser, GNRs, and bio-tissues, and provide the information in clinical applications to implement the concept of heterogeneity, which can enable the optimization of treatment parameters for superficial breast cancer treatment.

The Yo me cuido® Program: Addressing Breast Cancer Screening and Prevention Among Hispanic Women.

PubMed

Davis, Jenna L; Ramos, Roberto; Rivera-Colón, Venessa; Escobar, Myriam; Palencia, Jeannette; Grant, Cathy G; Green, B Lee

2015-09-01

Breast cancer is less likely to be diagnosed at the earliest stage in Hispanic/Latino (Hispanic) women compared to non-Hispanic White women, even after accounting for differences in age, socioeconomic status, and method of detection. Moffitt Cancer Center created a comprehensive health education program called Yo me cuido (®) (YMC) to address and reduce breast cancer disparities among Spanish- and English-speaking Hispanic women by providing breast cancer and healthy lifestyles awareness and education, and promoting breast cancer screenings, reminders, and referrals for women 40 years and older. The purpose of this paper is to showcase the innovative approaches and methods to cancer prevention and early detection of the YMC program, and to promote it as an effective tool for improving outcomes in community health education, outreach, and engagement activities with Hispanic populations. Key components of the program include educational workshops, mammogram referrals, and a multimedia campaign. The YMC program is unique because of its approaches in reaching the Hispanic population, such as delivering the program with compassionate services to empower participants to live a healthier lifestyle. Additionally, direct follow-up for mammography screenings is provided by program staff. From 2011 to 2013, YMC has educated 2,226 women and 165 men through 93 workshops. About 684 (52 %) women ages 40 and older have had a screening mammogram within their first year of participating in the program. The YMC program is an innovative cancer education and outreach program that has demonstrated a positive impact on the lives of the Hispanic community in the Tampa Bay region.

The Federal Nursing Services Award. Enlisted women with breast cancer: balancing demands and expectations.

PubMed

Wilmoth, Margaret Chamberlain

2003-07-01

Diagnosis with breast cancer is not an automatic cause for discharge from the military. Therefore, it is important to know how this disease impacts enlisted women in the military. This study describes how enlisted women manage diagnosis and treatment within the context of their military careers. Grounded theory guided the study methodology. Audiotaped semistructured interviews were conducted three times over 9 months to learn how treatment impacted work demands. Data saturation was attained after 46 interviews were conducted. Participants had to balance demands and expectations among the Military Career and Military Medical Subsystems and their Social Support Subsystem. Support from the chain of command was critical in women's ability to balance demands and expectations of career, family, and illness. Military nurses are in a unique position to create strategies that will assist enlisted women in coping with breast cancer.

NASA SMART Probe: Breast Cancer Application

NASA Technical Reports Server (NTRS)

Mah, Robert W.; Norvig, Peter (Technical Monitor)

2000-01-01

There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

Identification of potential compensatory muscle strategies in a breast cancer survivor population: A combined computational and experimental approach.

PubMed

Chopp-Hurley, Jaclyn N; Brookham, Rebecca L; Dickerson, Clark R

2016-12-01

Biomechanical models are often used to estimate the muscular demands of various activities. However, specific muscle dysfunctions typical of unique clinical populations are rarely considered. Due to iatrogenic tissue damage, pectoralis major capability is markedly reduced in breast cancer population survivors, which could influence arm internal and external rotation muscular strategies. Accordingly, an optimization-based muscle force prediction model was systematically modified to emulate breast cancer population survivors through adjusting pectoralis capability and enforcing an empirical muscular co-activation relationship. Model permutations were evaluated through comparisons between predicted muscle forces and empirically measured muscle activations in survivors. Similarities between empirical data and model outputs were influenced by muscle type, hand force, pectoralis major capability and co-activation constraints. Differences in magnitude were lower when the co-activation constraint was enforced (-18.4% [31.9]) than unenforced (-23.5% [27.6]) (p<0.0001). This research demonstrates that muscle dysfunction in breast cancer population survivors can be reflected through including a capability constraint for pectoralis major. Further refinement of the co-activation constraint for survivors could improve its generalizability across this population and activities. Improving biomechanical models to more accurately represent clinical populations can provide novel information that can help in the development of optimal treatment programs for breast cancer population survivors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Opportunities for public health communication, intervention, and future research on breast cancer in younger women.

PubMed

Buchanan, Natasha; Roland, Katherine B; Rodriguez, Juan L; Miller, Jacqueline W; Fairley, Temeika

2013-04-01

Approximately 6% of breast cancers in the United States occur in women under the age of 40 years. Compared with women ≥40 years of age, younger women are diagnosed at later stages, have higher rates of recurrence and death, and may be predisposed to secondary breast or ovarian cancer. An informal meeting of experts discussed opportunities for research and public health communication related to breast cancer among young (<40 and/or premenopausal) women. In September 2011, the Centers for Disease Control and Prevention hosted 18 experts in oncology, genetics, behavioral science, survivorship and advocacy, public health, communication, ethics, nutrition, physical activity, and environmental health. They (1) reviewed research and programmatic knowledge on risk and preventive factors, early detection, and survivorship; and (2) discussed ideas for research, communication, and programmatic efforts related to young women diagnosed with or at risk for early onset breast cancer. Levels of evidence and themes for future research regarding risk and preventive factors, including exposures, were discussed. Early detection strategies, including screening, risk assessment, and genetic counseling, as well as survivorship issues, follow-up care, fertility and reproductive health, and psychosocial care were highlighted. Community and academic researchers, providers, advocates, and the federal public health community discussed strategies and opportunities for this unique population. Although the evidence is limited, future research and communication activities may be useful to organize future public health initiatives.

Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK2 Inhibitor for Treatment of Triple-negative Breast Cancer with a Compromised G1/S Checkpoint.

PubMed

Zhu, Dan; Xu, Shuichan; Deyanat-Yazdi, Gordafaried; Peng, Sophie X; Barnes, Leo A; Narla, Rama Krishna; Tran, Tam; Mikolon, David; Ning, Yuhong; Shi, Tao; Jiang, Ning; Raymon, Heather K; Riggs, Jennifer R; Boylan, John F

2018-06-04

Historically, phenotypic-based drug discovery has yielded a high percentage of novel drugs while uncovering new tumor biology. CC-671 was discovered using a phenotypic screen for compounds that preferentially induced apoptosis in triple negative breast cancer cell lines while sparing luminal breast cancer cell lines. Detailed in vitro kinase profiling shows CC-671 potently and selectively inhibits two kinases-TTK and CLK2. Cellular mechanism of action studies demonstrate that CC-671 potently inhibits the phosphorylation of KNL1 and SRp75, direct TTK and CLK2 substrates, respectively. Furthermore, CC-671 causes mitotic acceleration and modification of pre-mRNA splicing leading to apoptosis, consistent with cellular TTK and CLK inhibition. Correlative analysis of genomic and potency data against a large panel of breast cancer cell lines identifies breast cancer cells with a dysfunctional G1/S checkpoint as more sensitive to CC-671, suggesting synthetic lethality between G1/S checkpoint and TTK/CLK2 inhibition. Furthermore, significant in vivo CC-671 efficacy was demonstrated in two cell line-derived and one patient tumor-derived xenograft models of TNBC following weekly dosing. These findings are the first to demonstrate the unique inhibitory combination activity of a dual TTK/CLK2 inhibitor that preferably kills TNBC cells and shows synthetic lethality with a compromised G1/S checkpoint in breast cancer cell lines. Based on these data, CC-671 was moved forward for clinical development as a potent and selective TTK/CLK2 inhibitor in a subset of TNBC patients. Copyright ©2018, American Association for Cancer Research.

Ethnic disparities in breast cancer between Central Europe Caucasian women of Slavic origin and Middle East Turkish subjects.

PubMed

Zubor, P; Caliskan, M; Kajo, K; Soybir, G; Topuzlu, C; Danko, J

2013-09-20

The biological, cultural, behavioral and sociodemographic differences across populations modulate breast cancer profile among races or ethnics. Following this, we aimed to identify differences in breast cancer epidemiology, histopathology, and clinical presentation from representatives of central Europe (Slovakia) and Middle-East countries (Turkey) to point on ethnic disparities in cancer biology. The population based cross-sectional study analyzing 414 cases of primary breast carcinomas where 214 represented Caucasian and 200 Turkish subjects. The differences were found for age at the time of diagnosis (<0.0001), education, menopausal status (<0.001), tumor localization (<0.01), size (<0.0001), grade (<0.05) and axillary lymph node status (<0.001) between groups. Although carcinomas in Slovak subjects were of higher grade, negative axillary nodal status was more frequent finding compared to Turkish patients (50.0 vs. 41.0%). The Slovak group showed carcinomas to be more often ER positive (72.4 vs. 54.0%; <0.001), ER/PgR positive (54.6 vs. 49.0%; <0.001), of better Nottingham prognostic index (<0.001), and less frequent Her-2 positive (21.2 vs. 28.5%). Slovak population expressed significantly higher risk of non-sentinel lymph node metastases with increased tumor size, grade, vascular invasion and Her-2 positivity compared to Turkey population. The tumor size >2 cm and high tumor grade (G3) bears a risk of OR=7.62 and OR=3.10 in Slovak compared to OR=3.94 and OR=1.79 in Turkish cases, respectively.There are wide demographic and biological disparities in breast cancer between observed ethnics providing unique information for clinicians working at the level of screening or therapy in these populations. Keywords: breast cancer; ethnic; race; disparity; cancer biology.

CXCR4 in breast cancer: oncogenic role and therapeutic targeting

PubMed Central

Xu, Chao; Zhao, Hong; Chen, Haitao; Yao, Qinghua

2015-01-01

Chemokines are 8–12 kDa peptides that function as chemoattractant cytokines and are involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled seven-span transmembrane receptors. Chemokines play a fundamental role in the regulation of a variety of cellular, physiological, and developmental processes. Their aberrant expression can lead to a variety of human diseases including cancer. C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12). CXCR4 belongs to the superfamily of the seven transmembrane domain heterotrimeric G protein-coupled receptors and is functionally expressed on the cell surface of various types of cancer cells. CXCR4 also plays a role in the cell proliferation and migration of these cells. Recently, CXCR4 has been reported to play an important role in cell survival, proliferation, migration, as well as metastasis of several cancers including breast cancer. This review is mainly focused on the current knowledge of the oncogenic role and potential drugs that target CXCR4 in breast cancer. Additionally, CXCR4 proangiogenic molecular mechanisms will be reviewed. Strict biunivocal binding affinity and activation of CXCR4/CXCL12 complex make CXCR4 a unique molecular target for prevention and treatment of breast cancer. PMID:26356032

Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases.

PubMed

Choy, Cecilia; Ansari, Khairul I; Neman, Josh; Hsu, Sarah; Duenas, Matthew J; Li, Hubert; Vaidehi, Nagarajan; Jandial, Rahul

2017-04-26

Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. The neural niche poses unique selection pressures, and neoplastic cells that utilize the brain microenvironment may have a survival advantage. Tropomyosin-related kinase B (TrkB), Her2, and downstream targets were analyzed in primary breast cancer, breast-to-brain metastasis (BBM) tissues, and tumor-derived cell lines using quantitative real-time PCR, western blot, and immunohistochemical assessment. TrkB function on BBM was confirmed with intracranial, intracardiac, or mammary fat pad xenografts in non-obese diabetic/severe combined immunodeficiency mice. The function of brain-derived neurotrophic factor (BDNF) on cell proliferation and TrkB/Her2 signaling and interactions were confirmed using selective shRNA knockdown and selective inhibitors. The physical interaction of Her2-TrkB was analyzed using electron microscopy, co-immunoprecipitation, and in silico analysis. Dual targeting of Her2 and TrkB was analyzed using clinically utilized treatments. We observed that patient tissues and cell lines derived from Her2+ human BBM displayed increased activation of TrkB, a neurotrophin receptor. BDNF, an extracellular neurotrophin, with roles in neuronal maturation and homeostasis, specifically binds to TrkB. TrkB knockdown in breast cancer cells led to decreased frequency and growth of brain metastasis in animal models, suggesting that circulating breast cancer cells entering the brain may take advantage of paracrine BDNF-TrkB signaling for colonization. In addition, we investigated a possible interaction between TrkB and Her2 receptors on brain metastatic breast cancer cells, and found that BDNF phosphorylated both its cognate TrkB receptor and the Her2 receptor in brain metastatic breast cancer cells. Collectively, our findings suggest that heterodimerization of Her2 and TrkB receptors gives breast cancer cells a survival advantage in the brain and that dual inhibition of these receptors may hold therapeutic potential.

Mammography screening. Benefits, harms, and informed choice.

PubMed

Jørgensen, Karsten Juhl

2013-04-01

The rationale for breast cancer screening with mammography is deceptively simple: catch it early and reduce mortality from the disease and the need for mastectomies. But breast cancer is a complex problem, and complex problems rarely have simple solutions. Breast screening brings forward the time of diagnosis only slightly compared to the lifetime of a tumour, and screen-detected tumours have a size where metastases are possible. A key question is if screening can prevent metastases, and if the screen-detected tumours are small enough to allow breast conserving surgery rather than mastectomy. A mortality reduction can never justify a medical intervention in its own right, but must be weighed against the harms. Overdiagnosis is the most important harm of breast screening, but has gained wider recognition only in recent years. Screening leads to the detection and treatment of breast cancers that would otherwise never have been detected because they grow very slowly or not at all and would not have been detected in the woman's lifetime in the absence of screening. Screening therefore turns women into cancer patients unnecessarily, with life-long physical and psychological harms. The debate about the justification of breast screening is therefore not a simple question of whether screening reduces breast cancer mortality. This dissertation quantifies the primary benefits and harms of screening mammography. Denmark has an unscreened "control group" because only two geographical regions offered screening over a long time-period, which is unique in an international context. This was used to study breast cancer mortality, overdiagnosis, and the use of mastectomies. Also, a systematic review of overdiagnosis in five other countries allowed us to show that about half of the screen-detected breast cancers are overdiagnosed. An effect on breast cancer mortality is doubtful in today's setting, and overdiagnosis causes an increase in the use of mastectomies. These findings are discussed in the context of tumour biology and stage at diagnosis. The information provided to women in invitations and on the Internet exaggerates benefits, participation is directly recommended, and the harms are downplayed or left out, despite agreement that the objective is informed choice. This raises an ethical discussion concerning autonomy versus paternalism, and the difficulty in weighing benefits against harms. Finally, financial, political, and professional conflicts of interest are discussed, as well as health economics.

Cold Atmospheric Plasma for Selectively Ablating Metastatic Breast Cancer Cells

PubMed Central

Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

2013-01-01

Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atomospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy. PMID:24040051

Socioeconomic status and quality of life among Chinese American breast cancer survivors: The mediating roles of social support and social constraints.

PubMed

You, Jin; Wang, Carol; Yeung, Nelson Chun Yiu; Lu, Qian

2018-03-30

Literature has well noted ethnic/racial disparities in cancer survival and cancer care. However, socioeconomic disparities in psychosocial adjustment to breast cancer have garnered little attention. This study addresses the research gap by investigating the associations between socioeconomic indicators (ie, education, annual personal, and household income) and quality of life (QOL) and the mediating roles of social support and social constraints (objective and subjective conditions that constrain individuals from disclosing cancer concerns) in these associations among Chinese American breast cancer survivors (CABCS). Ninety-six CABCS completed questionnaires assessing these variables. After controlling for stage of cancer, annual personal and household income had indirect effects on QOL through social support, and education showed indirect effect on QOL through social support and social constraints. Subscale analyses indicated that controlling for years of immigration, annual personal and household income showed indirect effect on functional well-being through social support. When controlling for stage of cancer and income, education showed indirect effects on physical well-being through social support and social constraints and showed both direct and indirect effects on breast cancer concerns through social constraints. This study suggested that socioeconomic indicators, education, and income could be associated with different aspects of QOL through unique interpersonal mechanisms among CABCS. Our findings implied that increasing social support and reducing social constraints when implementing psychosocial interventions for CABCS may help to address the SES-related health disparities. Copyright © 2018 John Wiley & Sons, Ltd.

Guideline implementation for breast healthcare in low- and middle-income countries: breast healthcare program resource allocation.

PubMed

Harford, Joe; Azavedo, Edward; Fischietto, Mary

2008-10-15

Breast cancer is serious public health problem in countries of all resource levels. Although major advances in the detection and treatment of the disease have occurred in higher income settings, similar progress has been slow or scarce in most low- and middle-income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to better outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to screening/treatment facilities, inadequate supplies of necessary drugs, and timeliness of treatment after diagnosis. Clearly, these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues in HCS that hinder the delivery of breast health services, the BHGI Healthcare Systems and Public Policy Panel explored the HCS structures and function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this panel were expressed in terms of 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to HCS that are important to consider when designing, implementing, and measuring the performance of a BCP. Health ministers, other policymakers, healthcare personnel, administrators, and anyone else involved in developing a BCP can use and adapt this framework to improve outcomes and ensure the more effective use of resources. (c) 2008 American Cancer Society.

A paraneoplastic manifestation of metastatic breast cancer responding to endocrine therapy: a case report

PubMed Central

Wood, Joanna P; Haynes, Andrew P; Cheung, KL

2008-01-01

Background Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment. Case presentation We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms. Conclusion This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause. It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms. PMID:19087318

A paraneoplastic manifestation of metastatic breast cancer responding to endocrine therapy: a case report.

PubMed

Wood, Joanna P; Haynes, Andrew P; Cheung, K L

2008-12-16

Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment. We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms. This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause.It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.

Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer.

PubMed

Bartolacci, Caterina; Andreani, Cristina; Amici, Augusto; Marchini, Cristina

2018-01-01

It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial effects. Among them, resveratrol, a phytoalexin found in numerous plant species, and more notably in grapes, has widely piqued the interest of the scientific community by virtue of its anti-aging, anti-inflammatory and anti-oxidant properties. Moreover, evidence claiming resveratrol ability to hinder processes underlying all the three steps of carcinogenesis (tumor initiation, progression and metastasization) has propelled an incredibly massive number of studies aimed at enquiring its eventual clinical potential in the fight against cancer. However, despite a large body of data pointing to the advantages of dietary resveratrol intake in respect of certain disease conditions, and cancer inter alia, its real position still remains quite ambiguous. In this uncertain scenario, the present review focuses its attention on the highly entangled relationship between resveratrol and breast cancer, attempting to shape the plethora of controversial results stemming from studies carried out on several in vitro and in vivo breast cancer models. Coping with such a tricky matter, there are so many variabilities concerning both resveratrol itself (dosage, administration, bioavailabilty, among others) and the unique molecular traits of each specific breast cancer subtype that must be taken into account when facing the dilemma: "might resveratrol be protective against breast cancer or does it rather fuel it?". Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

I wanted you to know: Breast cancer survivors' control of workplace communication about cancer.

PubMed

Robinson, Lynne; Kocum, Lucie; Loughlin, Catherine; Bryson, Lindsay; Dimoff, Jennifer K

2015-10-01

Of working women diagnosed with cancer, approximately one-third will have breast cancer. Communicating about their cancer plays an important role in their workplace experience. It is challenging but helpful in eliciting needed social support and accommodations. Fully understanding such communication experiences is important in order to facilitate the well-being and success of such women in their workplaces. A qualitative study permits a richer account of the details of these workplace communications, and a deeper understanding of how women manage the complex and multifaceted communication process. This study used thematic analysis of semistructured interviews from 19 women working full time at the time of their breast cancer diagnosis. We found 3 themes that encapsulated unfolding individual experiences, representing a complex interplay of challenges to maintaining a sense of personal control in workplace responses: challenges to control posed by the experience of sharing information in the workplace about the woman's cancer, women's very individual attempts to control how information about their cancer was shared, and the mixed responses of those who were told. The result was unique individual trajectories in which empathic responses tailored to the individual's needs and preferences were most helpful. These findings can provide guidance on managing cancer communication for survivors, and on how to best support and accommodate women workers with breast cancer, facilitating their ability to control how their cancer impacts their work experience. Our website (http://www.iwantedyoutoknow.ca/) provides a video, tip sheet, and other resources for facilitating supportive communication in the workplace. (c) 2015 APA, all rights reserved).

Altering calcium influx for selective destruction of breast tumor.

PubMed

Yu, Han-Gang; McLaughlin, Sarah; Newman, Mackenzie; Brundage, Kathleen; Ammer, Amanda; Martin, Karen; Coad, James

2017-03-04

Human triple-negative breast cancer has limited therapeutic choices. Breast tumor cells have depolarized plasma membrane potential. Using this unique electrical property, we aim to develop an effective selective killing of triple-negative breast cancer. We used an engineered L-type voltage-gated calcium channel (Cec), activated by membrane depolarization without inactivation, to induce excessive calcium influx in breast tumor cells. Patch clamp and flow cytometry were used in testing the killing selectivity and efficiency of human breast tumor cells in vitro. Bioluminescence and ultrasound imaging were used in studies of human triple-negative breast cancer cell MDA-MB-231 xenograft in mice. Histological staining, immunoblotting and immunohistochemistry were used to investigate mechanism that mediates Cec-induced cell death. Activating Cec channels expressed in human breast cancer MCF7 cells produced enormous calcium influx at depolarized membrane. Activating the wild-type Cav1.2 channels expressed in MCF7 cells also produced a large calcium influx at depolarized membrane, but this calcium influx was diminished at the sustained membrane depolarization due to channel inactivation. MCF7 cells expressing Cec died when the membrane potential was held at -10 mV for 1 hr, while non-Cec-expressing MCF7 cells were alive. MCF7 cell death was 8-fold higher in Cec-expressing cells than in non-Cec-expressing cells. Direct injection of lentivirus containing Cec into MDA-MB-231 xenograft in mice inhibited tumor growth. Activated caspase-3 protein was detected only in MDA-MB-231 cells expressing Cec, along with a significantly increased expression of activated caspase-3 in xenograft tumor treated with Cec. We demonstrated a novel strategy to induce constant calcium influx that selectively kills human triple-negative breast tumor cells.

Co-evolution of breast-to-brain metastasis and neural progenitor cells.

PubMed

Neman, Josh; Choy, Cecilia; Kowolik, Claudia M; Anderson, Athena; Duenas, Vincent J; Waliany, Sarah; Chen, Bihong T; Chen, Mike Y; Jandial, Rahul

2013-08-01

Brain colonization by metastatic tumor cells offers a unique opportunity to investigate microenvironmental influences on the neoplastic process. The bi-directional interplay of breast cancer cells (mesodermal origin) and brain cells (neuroectodermal origin) is poorly understood and rarely investigated. In our patients undergoing neurosurgical resection of breast-to-brain metastases, specimens from the tumor/brain interface exhibited increased active gliosis as previously described. In addition, our histological characterization revealed infiltration of neural progenitor cells (NPCs) both outside and inside the tumor margin, leading us to investigate the cellular and molecular interactions between NPCs and metastases. Since signaling by the TGF-β superfamily is involved in both developmental neurobiology and breast cancer pathogenesis, we examined the role of these proteins in the context of brain metastases. The brain-metastatic breast cancer cell line MDA-MB-231Br (231Br) expressed BMP-2 at significantly higher levels compared to its matched primary breast cancer cell line MDA-MB-231 (231). Co-culturing was used to examine bi-directional cellular effects and the relevance of BMP-2 overexpression. When co-cultured with NPCs, 231 (primary) tumor cells failed to proliferate over 15 days. However, 231Br (brain metastatic) tumor cells co-cultured with NPCs escaped growth inhibition after day 5 and proliferated, occurring in parallel with NPC differentiation into astrocytes. Using shRNA and gene knock-in, we then demonstrated BMP-2 secreted by 231Br cells mediated NPC differentiation into astrocytes and concomitant tumor cell proliferation in vitro. In xenografts, overexpression of BMP-2 in primary breast cancer cells significantly enhanced their ability to engraft and colonize the brain, thereby creating a metastatic phenotype. Conversely, BMP-2 knockdown in metastatic breast cancer cells significantly diminished engraftment and colonization. The results suggest metastatic tumor cells create a permissive neural niche by steering NPC differentiation toward astrocytes through paracrine BMP-2 signaling.

Co-evolution of breast-to-brain metastasis and neural progenitor cells

PubMed Central

Neman, Josh; Choy, Cecilia; Kowolik, Claudia M.; Anderson, Athena; Duenas, Vincent J.; Waliany, Sarah; Chen, Bihong T.; Chen, Mike Y.

2013-01-01

Brain colonization by metastatic tumor cells offers a unique opportunity to investigate microenvironmental influences on the neoplastic process. The bi-directional interplay of breast cancer cells (mesodermal origin) and brain cells (neuroectodermal origin) is poorly understood and rarely investigated. In our patients undergoing neurosurgical resection of breast-to-brain metastases, specimens from the tumor/brain interface exhibited increased active gliosis as previously described. In addition, our histological characterization revealed infiltration of neural progenitor cells (NPCs) both outside and inside the tumor margin, leading us to investigate the cellular and molecular interactions between NPCs and metastases. Since signaling by the TGF-β superfamily is involved in both developmental neurobiology and breast cancer pathogenesis, we examined the role of these proteins in the context of brain metastases. The brain-metastatic breast cancer cell line MDA-MB-231Br (231Br) expressed BMP-2 at significantly higher levels compared to its matched primary breast cancer cell line MDA-MB-231 (231). Co-culturing was used to examine bi-directional cellular effects and the relevance of BMP-2 overexpression. When co-cultured with NPCs, 231 (primary) tumor cells failed to proliferate over 15 days. However, 231Br (brain meta-static) tumor cells co-cultured with NPCs escaped growth inhibition after day 5 and proliferated, occurring in parallel with NPC differentiation into astrocytes. Using shRNA and gene knock-in, we then demonstrated BMP-2 secreted by 231Br cells mediated NPC differentiation into astrocytes and concomitant tumor cell proliferation in vitro. In xenografts, overexpression of BMP-2 in primary breast cancer cells significantly enhanced their ability to engraft and colonize the brain, thereby creating a metastatic phenotype. Conversely, BMP-2 knockdown in metastatic breast cancer cells significantly diminished engraftment and colonization. The results suggest metastatic tumor cells create a permissive neural niche by steering NPC differentiation toward astrocytes through paracrine BMP-2 signaling. PMID:23456474

FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target

PubMed Central

Horton, Janet K.; Siamakpour-Reihani, Sharareh; Lee, Chen-Ting; Zhou, Ying; Chen, Wei; Geradts, Joseph; Fels, Diane R.; Hoang, Peter; Ashcraft, Kathleen A.; Groth, Jeff; Kung, Hsiu-Ni; Dewhirst, Mark W.; Chi, Jen-Tsan A.

2015-01-01

Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. In this study, we utilized RNA samples for microarray analysis from two sources: 1. Paired pre- and postirradiation breast tumor tissue from 32 early-stage breast cancer patients treated in our unique preoperative radiation Phase I trial; and 2. Sixteen biologically diverse breast tumor cell lines exposed to 0 and 5 Gy irradiation. The transcriptome response to radiation exposure was derived by comparing gene expression in samples before and after irradiation. Genes with the highest coefficient of variation were selected for further evaluation and validated at the RNA and protein level. Gene editing and agonistic antibody treatment were performed to assess the impact of gene modulation on radiation response. Gene expression in our cohort of luminal breast cancer patients was distinctly different before and after irradiation. Further, two distinct patterns of gene expression were observed in our biologically diverse group of breast cancer cell lines pre- versus postirradiation. Cell lines that showed significant change after irradiation were largely luminal subtype, while gene expression in the basal and HER2+ cell lines was minimally impacted. The 100 genes with the most significant response to radiation in patients were identified and analyzed for differential patterns of expression in the radiation-responsive versus nonresponsive cell lines. Fourteen genes were identified as significant, including FAS, a member of the tumor necrosis factor receptor family known to play a critical role in programed cell death. Modulation of FAS in breast cancer cell lines altered radiation response phenotype and enhanced radiation sensitivity in radioresistant basal cell lines. Our findings suggest that cell-type-specific, radiation-induced FAS contributes to subtype-specific breast cancer radiation response and that activation of FAS pathways may be exploited for biologically tailored radiotherapy. PMID:26488758

Identification of a PEAK1/ZEB1 signaling axis during TGFβ/fibronectin-induced EMT in breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agajanian, Megan; Runa, Farhana; Kelber, Jonathan A., E-mail: jonathan.kelber@csun.edu

Transforming Growth Factor beta (TGFβ) is the archetypal member of the TGFβ superfamily of ligands and has pleiotropic functions during normal development, adult tissue homeostasis and pathophysiological processes such as cancer. In epithelial cancers TGFβ signaling can either suppress tumor growth or promote metastasis via the induction of a well-characterized epithelial–mesenchymal transition (EMT) program. We recently reported that PEAK1 kinase mediates signaling cross talk between TGFβ receptors and integrin/Src/MAPK pathways and functions as a critical molecular regulator of TGFβ-induced breast cancer cell proliferation, migration, EMT and metastasis. Here, we examined the breast cancer cell contexts in which TGFβ induces bothmore » EMT and PEAK1, and discovered this event to be unique to oncogene-transformed mammary epithelial cells and triple-negative breast cancer cells. Using the Cancer BioPortal database, we identified PEAK1 co-expressors across multiple malignancies that are also common to the TGFβ response gene signature (TBRS). We then used the ScanSite database to identify predicted protein–protein binding partners of PEAK1 and the PEAK1-TBRS co-expressors. Analysis of the Cytoscape interactome and Babelomics-derived gene ontologies for a novel gene set including PEAK1, CRK, ZEB1, IL11 and COL4A1 enabled us to hypothesize that PEAK1 may be regulating TGFβ-induced EMT via its interaction with or regulation of these other genes. In this regard, we have demonstrated that PEAK1 is necessary for TGFβ to induce ZEB1-mediated EMT in the context of fibronectin/ITGB3 activation. These studies and future mechanistic studies will pave the way toward identifying the context in which TGFβ blockade may significantly improve breast cancer patient outcomes. - Highlights: • PEAK1 is upregulated in mammary epithelial cells during TGFβ-induced EMT. • TGFβ-induced EMT upregulates PEAK1 in triple negative breast cancer. • PEAK1 is necessary for TGFβ/fibronectin-induced ZEB1 expression during EMT. • The PEAK1/CRK/ZEB1 pathway is a novel target for blocking EMT in breast cancer.« less

Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer.

PubMed

Delli Carpini, Jennifer; Carpini, Jennifer Delli; Karam, Amer K; Montgomery, Leslie

2010-03-01

Tumor neovascularization is a complex process that plays a crucial role in the development of many different types of cancer. Vascular endothelial growth factor (VEGF) is a potent mitogen that is involved with mitogenesis, angiogenesis, endothelial survival, and the induction of hematopoiesis. By increasing vascular permeability in endothelial cells, it helps tumors recruit wound-healing proteins fibrin and fibrinogen from the plasma, suggesting that tumor formation is a process of abnormal wound healing dependent on the ability to generate a blood supply. The human female reproductive tract is highly dependent on VEGF for normal functions such as endometrial proliferation and development of the corpus luteum. The unique influence of female sex steroid hormones on the expression and activity of VEGF deems angiogenesis an important facet of the development of breast and ovarian cancer. Additionally, the up-regulation of VEGF by the E6 oncoprotein of the human papillomavirus suggests that VEGF plays an important role in the development of cervical cancer. Clinical trials have investigated the humanized monoclonal antibody bevacizumab as potential treatment for all three forms of cancer; the data show that in breast cancer, the use of bevacizumab may lengthen the disease-free survival for women with advanced breast cancer, but does not appear to change their overall survival. It may have a role as salvage chemotherapy for ovarian and cervical cancer, though further research is needed to establish it as a definitive form of treatment.

In Situ Electrochemical Sensing and Real-Time Monitoring Live Cells Based on Freestanding Nanohybrid Paper Electrode Assembled from 3D Functionalized Graphene Framework.

PubMed

Zhang, Yan; Xiao, Jian; Lv, Qiying; Wang, Lu; Dong, Xulin; Asif, Muhammad; Ren, Jinghua; He, Wenshan; Sun, Yimin; Xiao, Fei; Wang, Shuai

2017-11-08

In this work, we develop a new type of freestanding nanohybrid paper electrode assembled from 3D ionic liquid (IL) functionalized graphene framework (GF) decorated by gold nanoflowers (AuNFs), and explore its practical application in in situ electrochemical sensing of live breast cell samples by real-time tracking biomarker H 2 O 2 released from cells. The AuNFs modified IL functionalized GF (AuNFs/IL-GF) was synthesized via a facile and efficient dopamine-assisted one-pot self-assembly strategy. The as-obtained nanohybrid assembly exhibits a typical 3D hierarchical porous structure, where the highly active electrocatalyst AuNFs are well dispersed on IL-GF scaffold. And the graft of hydrophilic IL molecules (i.e., 1-butyl-3-methylimidazolium tetrafluoroborate, BMIMBF 4 ) on graphene nanosheets not only avoids their agglomeration and disorder stacking during the self-assembly but also endows the integrated IL-GF monolithic material with unique hydrophilic properties, which enables it to be readily dispersed in aqueous solution and processed into freestanding paperlike material. Because of the unique structural properties and the combinational advantages of different components in the AuNFs/IL-GF composite, the resultant nanohybrid paper electrode exhibits good nonenzymatic electrochemical sensing performance toward H 2 O 2 . When used in real-time tracking H 2 O 2 secreted from different breast cells attached to the paper electrode without or with radiotherapy treatment, the proposed electrochemical sensor based on freestanding AuNFs/IL-GF paper electrode can distinguish the normal breast cell HBL-100 from the cancer breast cells MDA-MB-231 and MCF-7 cells, and assess the radiotherapy effects to different breast cancer cells, which opens a new horizon in real-time monitoring cancer cells by electrochemical sensing platform.

Activity of Nanobins Loaded with Cisplatin and Arsenic Trioxide in Primary and Metastatic Breast Cancer

NASA Astrophysics Data System (ADS)

Swindell, Elden Peter, III

Despite recent advances in breast cancer screening and detection, the disease is still a leading cause of death for women of all ages. Young, African-American women are disproportionally affected with a type of breast cancer, triple-negative breast cancer, which is particularly difficult to treat and has the worst prognosis of any breast cancer subtype. These tumors often spread to the lungs, liver, bones and brains of patients, which is ultimately fatal. This dissertation presents results from a series of in vivo and in vitro experiments that investigate the clinical utility of a novel nanoparticulate formulation of cisplatin and arsenic trioxide, NB(Pt,As) for treating primary and metastatic triple-negative breast cancer. These nanobins consist of a solid, crystalline metal nanoparticle surrounded by a lipid bilayer with 80-90 nm diameter. This drug payload is extremely stable, and so NB(Pt,As) is extremely well tolerated in mice. Furthermore, NB(Pt,As) is effective in two different mouse models of breast cancer, one of primary tumor growth an another of lung metastases. A discovery presented here, that thiol containing compounds are required for drug release, may explain these seemingly incongruous results. The large amount of intracellular thiol can trigger drug release, while the low concentration of free thiols in blood is insufficient to cause drug release. To improve the treatment of brain tumors with this unique drug, we added transferrin to the surface of the nanobin using copper-catalyzed "click" chemistry, which preserves protein activity. The addition of transferrin to the nanobins enables 10 fold greater uptake in the brains of mice treated with the transferrin-targeted nanobins Tf-NB(Pt,A) compared to NB(Pt,As). By penetrating the blood brain barrier, the Tf-NB(Pt,As) was able to reduce breast cancer metastases in the brains of mice, whereas NB(Pt,As) had no effect. Taken together, these results demonstrate the intricate balance of drug release properties and seemingly subtle changes in drug design can have a profound impact on anti-tumor efficacy.

Study protocol for Young & Strong: a cluster randomized design to increase attention to unique issues faced by young women with newly diagnosed breast cancer.

PubMed

Greaney, Mary L; Sprunck-Harrild, Kim; Ruddy, Kathryn J; Ligibel, Jennifer; Barry, William T; Baker, Emily; Meyer, Meghan; Emmons, Karen M; Partridge, Ann H

2015-01-31

Each year, approximately 11% of women diagnosed with breast cancer in the United States are 45 years of age or younger. These women have concerns specific to or accentuated by their age, including fertility-related concerns, and have higher rates of psychosocial distress than women diagnosed at older ages. Current guidelines recommend that fertility risks be considered early in all treatment plans; however, the extant research indicates that attention to fertility by the healthcare team is limited. Importantly, attention to fertility may be a proxy for whether or not other important issues warranting attention in younger women with breast cancer are addressed, including genetic risks, psychosocial distress, sexual functioning, and body image concerns. The Young & Strong study tests the efficacy of an intervention designed for young women recently diagnosed with breast cancer and their oncologists with the intention to: 1) increase attention to fertility as an important surrogate for other issues facing young women, 2) educate and support young women and their providers, and 3) reduce psychosocial distress among young women with breast cancer. The study employs a cluster randomized design including 14 academic institutions and 40 community sites across the U.S. assigned to either the study intervention arm or contact-time comparison intervention arm. Academic institutions enroll up to 15 patients per site while community sites enroll up to 10 patients. Patient eligibility requirements include: an initial diagnosis of stage I-III invasive breast cancer within three months prior, without a known recurrence or metastatic breast cancer; 18-45 years of age at diagnosis; ability to read and write in English. The primary outcome is oncologists' attention to fertility concerns as determined by medical record review. Secondary outcomes include differences in patient satisfaction with care and psychosocial distress between the two study arms. Study findings will provide valuable insight into how to increase attention to fertility and other issues specific to young women with breast cancer and how to improve doctor-patient communication around these issues, which may promote better quality of care for this population. NCT01647607. Registered July 19, 2012.

Exploration of the family's role and strengths after a young woman is diagnosed with breast cancer: views of women and their families.

PubMed

Coyne, Elisabeth; Wollin, Judy; Creedy, Debra K

2012-04-01

This exploratory descriptive study examined the role and strengths of the family when supporting the younger woman (<50 years) after a diagnosis of breast cancer. The perspectives of women and family members were sought. Participants were recruited from oncology outpatient units in Australia. Semi-structured interviews guided by the Family Resiliency Framework were undertaken with 14 young women with breast cancer and 11 family members who reflected on the roles of family. Transcripts were analysed individually and in family groupings. Women with breast cancer and their family members experienced a range of emotions during the treatment period. Roles within the family changed as members responded to their circumstances. Analysis of interview transcripts identified the following primary themes; 'just being there', 'paradox of help' and 'buffer from society'. A secondary theme related to support, specifically 'the changing role of support for family members', highlighting the strengths and experiences of family. Recognition needs to be given to the complexity of changing roles experienced by young women with breast cancer and their families. Young women with breast cancer require unique forms of support because of the nature of their experience. Family roles were shaped through a shared sense of commitment and open communication amongst members. Families may demonstrate a range of strengths but are also vulnerable during this stressful period. Health professionals need to be aware of the possible needs of families, assess their adaptation to changing circumstances, and intervene through the provision of information, and counselling to enhance coping. Copyright © 2011 Elsevier Ltd. All rights reserved.

Learning from social media: utilizing advanced data extraction techniques to understand barriers to breast cancer treatment.

PubMed

Freedman, Rachel A; Viswanath, Kasisomayajula; Vaz-Luis, Ines; Keating, Nancy L

2016-07-01

Past examinations of breast cancer treatment barriers have typically included registry, claims-based, and smaller survey studies. We examined treatment barriers using a novel, comprehensive, social media analysis of online, candid discussions about breast cancer. Using an innovative toolset to search postings on social networks, message boards, patient communities, and topical sites, we performed a large-scale qualitative analysis. We examined the sentiments and barriers expressed about breast cancer treatments by Internet users during 1 year (2/1/14-1/31/15). We categorized posts based on thematic patterns and examined trends in discussions by race/ethnicity (white/black/Hispanic) when this information was available. We identified 1,024,041 unique posts related to breast cancer treatment. Overall, 57 % of posts expressed negative sentiments. Using machine learning software, we assigned treatment barriers for 387,238 posts (38 %). Barriers included emotional (23 % of posts), preferences and spiritual/religious beliefs (21 %), physical (18 %), resource (15 %), healthcare perceptions (9 %), treatment processes/duration (7 %), and relationships (7 %). Black and Hispanic (vs. white) users more frequently reported barriers related to healthcare perceptions, beliefs, and pre-diagnosis/diagnosis organizational challenges and fewer emotional barriers. Using a novel analysis of diverse social media users, we observed numerous breast cancer treatment barriers that differed by race/ethnicity. Social media is a powerful tool, allowing use of real-world data for qualitative research, capitalizing on the rich discussions occurring spontaneously online. Future research should focus on how to further employ and learn from this type of social intelligence research across all medical disciplines.

Racial and Ethnic Disparities in the Impact of Obesity on Breast Cancer Risk and Survival: A Global Perspective123

PubMed Central

Bandera, Elisa V; Maskarinec, Gertraud; Romieu, Isabelle; John, Esther M

2015-01-01

Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression. PMID:26567202

Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells

PubMed Central

Vasilatos, Shauna N.; Boric, Lamia; Shaw, Patrick G.; Davidson, Nancy E.

2013-01-01

Abnormal activities of histone lysine demethylases (KDMs) and lysine deacetylases (HDACs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms underlying the crosstalk between KDMs and HDACs in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDAC, but not NAD+ dependent class III HDAC, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer. PMID:21452019

Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective.

PubMed

Bandera, Elisa V; Maskarinec, Gertraud; Romieu, Isabelle; John, Esther M

2015-11-01

Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression. © 2015 American Society for Nutrition.

Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.

PubMed

Jeffery, Justin J; Lux, Katie; Vogel, John S; Herrera, Wynetta D; Greco, Stephen; Woo, Ho-Hyung; AbuShahin, Nisreen; Pagel, Mark D; Chambers, Setsuko K

2014-04-01

Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.

Cooperative Dynamics of AR and ER Activity in Breast Cancer

PubMed Central

D’Amato, Nicholas C.; Gordon, Michael A.; Babbs, Beatrice L.; Spoelstra, Nicole S.; Carson Butterfield, Kiel T.; Torkko, Kathleen C.; Phan, Vernon T.; Barton, Valerie N.; Rogers, Thomas J.; Sartorius, Carol A; Elias, Anthony D.; Gertz, Jason; Jacobsen, Britta M.; Richer, Jennifer K.

2016-01-01

Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha positive (ER+) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared to dihydrotestosterone (DHT). Estradiol-induced AR binding sites were enriched for estrogen response elements and had significant overlap with ER binding sites. Furthermore, AR inhibition reduced baseline and estradiol-mediated proliferation in multiple ER+/AR+ breast cancer cell lines, and synergized with tamoxifen and fulvestrant. In vivo, enzalutamide significantly reduced viability of tamoxifen-resistant MCF7 xenograft tumors and an ER+/AR+ patient-derived model. Enzalutamide also reduced metastatic burden following cardiac injection. Lastly, in a comparison of ER+/AR+ primary tumors versus patient-matched local recurrences or distant metastases, AR expression was often maintained even when ER was reduced or absent. These data provide pre-clinical evidence that anti-androgens that inhibit AR nuclear localization affect both AR and ER, and are effective in combination with current breast cancer therapies. In addition, single agent efficacy may be possible in tumors resistant to traditional endocrine therapy, since clinical specimens of recurrent disease demonstrate AR expression in tumors with absent or refractory ER. Implications This study suggests that AR plays a previously-unrecognized role in supporting E2-mediated ER activity in ER+/AR+ breast cancer cells, and that enzalutamide may be an effective therapeutic in ER+/AR+ breast cancers. PMID:27565181

"I'm Still Here": Resilience Among Older Survivors of Breast Cancer.

PubMed

Pieters, Huibrie C

2016-01-01

Cancer presents a severe adversity that calls on intrinsic strength factors such as resilience. Breast cancer is especially common among older women. Understanding the interaction between the mechanisms of resilience and the psychosocial impact of cancer requires consideration of developmental age. This research explores resilience from the point of view of older women who recently completed treatment for early-stage breast cancer. Constructivist grounded theory directed data collection and analysis of 31 personal, semistructured interviews with 18 women aged 70 to 94 years. Faced with overcoming the adversity of a first cancer experience, participants rebounded and restored balance to their lives with a sense that they did the work of managing cancer with self-efficacy and autonomy. Resilience was evidenced as a multidimensional process containing a natural interaction of attributes. Self-reliance, optimism, and persevering were embedded in human interconnectedness. The process of cancer survivorship was positioned in the larger picture of the joys and hardships of having lived a long life. The core self continued through these changing times, connecting the past, present, and anticipated future, as exemplified by "I'm still here." Regaining balance required tenacity, pragmatism, and dedication to do the work that needed to be done to treat cancer and move on with life. Resilience is a valuable resource in strength-based approaches in healthcare. Practical examples for clinicians who follow a strength-based approach to promote adaptation for the continuing challenges of breast cancer survivorship among older women include acknowledging unique individual expressions of resilience. Gero-oncology is a salient field for multidisciplinary teams who seek to study resilience.

Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells

PubMed Central

Guo, Shanchun; Liu, Mingli; Wang, Guangdi; Torroella-Kouri, Marta; Gonzalez-Perez, Ruben R.

2012-01-01

Significant correlations between obesity and incidence of various cancers have been reported. Obesity, considered a mild inflammatory process, is characterized by a high level of secretion of several cytokines from adipose tissue. These molecules have disparate effects, which could be relevant to cancer development. Among the inflammatory molecules, leptin, mainly produced by adipose tissue and overexpressed with its receptor (Ob-R) in cancer cells is the most studied adipokine. Mutations of leptin or Ob-R genes associated with obesity or cancer are rarely found. However, leptin is an anti-apoptotic molecule in many cell types, and its central roles in obesity-related cancers are based on its pro-angiogenic, pro-inflammatory and mitogenic actions. Notably, these leptin actions are commonly reinforced through entangled crosstalk with multiple oncogenes, cytokines and growth factors. Leptin-induced signals comprise several pathways commonly triggered by many cytokines (i.e, canonical: JAK2/STAT; MAPK/ERK1/2 and PI-3K/AKT1 and, non-canonical signaling pathways: PKC, JNK and p38 MAP kinase). Each of these leptin-induced signals is essential to its biological effects on food intake, energy balance, adiposity, immune and endocrine systems, as well as oncogenesis. This review is mainly focused on the current knowledge of the oncogenic role of leptin in breast cancer. Additionally, leptin pro-angiogenic molecular mechanisms and its potential role in breast cancer stem cells will be reviewed. Strict biunivocal binding-affinity and activation of leptin/Ob-R complex makes it a unique molecular target for prevention and treatment of breast cancer, particularly in obesity contexts. PMID:22289780

The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikonomov, Ognian C., E-mail: oikonomo@med.wayne.edu; Filios, Catherine, E-mail: cfilios@med.wayne.edu; Sbrissa, Diego, E-mail: dsbrissa@med.wayne.edu

2013-10-18

Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer,more » the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the homeostasis of these lipids in TNBC. Together, our results uncover an unexpected role for Sac3 phosphatase in TNBC cell proliferation. Database analyses, discussed herein, reinforce the involvement of Sac3 in breast cancer pathogenesis.« less

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

PubMed Central

Lehmann, Brian D.; Bauer, Joshua A.; Chen, Xi; Sanders, Melinda E.; Chakravarthy, A. Bapsi; Shyr, Yu; Pietenpol, Jennifer A.

2011-01-01

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PMID:21633166

Empowering Women through Education and Advocacy in Breast and Cervical Cancer Prevention and Control

Cancer.gov

Through partnerships with the Peruvian Ministry of Health and the Pan American Health Organization regional office, CGH co-supported the first Women’s Cancer Summit was held in Lima, Peru. This unique training workshop brought primary-level health care providers from 26 districts together with patient advocates and survivors from Peru, Bolivia, Colombia, and Ecuador.

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer*

PubMed Central

Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh; Nirujogi, Raja Sekhar; Kim, Min-Sik; Manda, Srikanth S.; Stearns, Vered; Gabrielson, Edward; Sukumar, Saraswati; Pandey, Akhilesh

2015-01-01

Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers. PMID:26330541

Opportunities for Public Health Communication, Intervention, and Future Research on Breast Cancer in Younger Women

PubMed Central

Buchanan, Natasha; Roland, Katherine B.; Rodriguez, Juan L.; Miller, Jacqueline W.; Fairley, Temeika

2015-01-01

Background Approximately 6% of breast cancers in the United States occur in women under the age of 40 years. Compared with women ≥ 40 years of age, younger women are diagnosed at later stages, have higher rates of recurrence and death, and may be predisposed to secondary breast or ovarian cancer. An informal meeting of experts discussed opportunities for research and public health communication related to breast cancer among young (< 40 and/or premenopausal) women. Methods In September 2011, the Centers for Disease Control and Prevention hosted 18 experts in oncology, genetics, behavioral science, survivorship and advocacy, public health, communication, ethics, nutrition, physical activity, and environmental health. They (1) reviewed research and programmatic knowledge on risk and preventive factors, early detection, and survivorship; and (2) discussed ideas for research, communication, and programmatic efforts related to young women diagnosed with or at risk for early onset breast cancer. Results Levels of evidence and themes for future research regarding risk and preventive factors, including exposures, were discussed. Early detection strategies, including screening, risk assessment, and genetic counseling, as well as survivorship issues, follow-up care, fertility and reproductive health, and psychosocial care were highlighted. Conclusion Community and academic researchers, providers, advocates, and the federal public health community discussed strategies and opportunities for this unique population. Although the evidence is limited, future research and communication activities may be useful to organize future public health initiatives. PMID:23514347

Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer

ClinicalTrials.gov

2018-04-26

Peripheral Neuropathy; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

ClinicalTrials.gov

2018-03-05

Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

Phosphoproteins in extracellular vesicles as candidate markers for breast cancer

PubMed Central

Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K.; Iliuk, Anton B.; Tao, W. Andy

2017-01-01

The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring. PMID:28270605

Phosphoproteins in extracellular vesicles as candidate markers for breast cancer.

PubMed

Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K; Iliuk, Anton B; Zhu, Jian-Kang; Tao, W Andy

2017-03-21

The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.

Exploring association between statin use and breast cancer risk: an updated meta-analysis.

PubMed

Islam, Md Mohaimenul; Yang, Hsuan-Chia; Nguyen, Phung-Anh; Poly, Tahmina Nasrin; Huang, Chih-Wei; Kekade, Shwetambara; Khalfan, Abdulwahed Mohammed; Debnath, Tonmoy; Li, Yu-Chuan Jack; Abdul, Shabbir Syed

2017-12-01

The benefits of statin treatment for preventing cardiac disease are well established. However, preclinical studies suggested that statins may influence mammary cancer growth, but the clinical evidence is still inconsistent. We, therefore, performed an updated meta-analysis to provide a precise estimate of the risk of breast cancer in individuals undergoing statin therapy. For this meta-analysis, we searched PubMed, the Cochrane Library, Web of Science, Embase, and CINAHL for published studies up to January 31, 2017. Articles were included if they (1) were published in English; (2) had an observational study design with individual-level exposure and outcome data, examined the effect of statin therapy, and reported the incidence of breast cancer; and (3) reported estimates of either the relative risk, odds ratios, or hazard ratios with 95% confidence intervals (CIs). We used random-effect models to pool the estimates. Of 2754 unique abstracts, 39 were selected for full-text review, and 36 studies reporting on 121,399 patients met all inclusion criteria. The overall pooled risks of breast cancer in patients using statins were 0.94 (95% CI 0.86-1.03) in random-effect models with significant heterogeneity between estimates (I 2  = 83.79%, p = 0.0001). However, we also stratified by region, the duration of statin therapy, methodological design, statin properties, and individual stain use. Our results suggest that there is no association between statin use and breast cancer risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

Octyl gallate and gallic acid isolated from Terminalia bellarica regulates normal cell cycle in human breast cancer cell lines.

PubMed

Sales, Mary Selesty; Roy, Anita; Antony, Ludas; Banu, Sakhila K; Jeyaraman, Selvaraj; Manikkam, Rajalakshmi

2018-07-01

Herbal medicines stand unique and effective in treating human diseases. Terminalia bellarica (T. bellarica) is a potent medicinal herb, with a wide range of pharmacological activities. The present study was aimed to evaluate the effect of octyl gallate (OG) and gallic acid (GA) isolated from methanolic fruit extract of T. bellirica to inhibit the survival of breast cancer cells (MCF-7 & MDA-MB-231). Both OG & GA exhibited decreased MCF-7 & MDA-MB-231 survival and induced apoptosis, with IC 50 value of OG and GA as 40 μM and 80 μM respectively. No toxic effect was observed on normal breast cells (MCF-10A). The compounds inhibited cell cycle progression by altering the expression of the cell cycle regulators (Cyclin D1, D3, CDK-4, CDK-6, p18 INK4, p21Waf-1 and p27 KIP). Octyl gallate was more effective at low concentrations than GA. In-silico results provided stable interactions between the compounds and target proteins. The present investigation proved the downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators inducing apoptosis in compound-treated breast cancer cells. Hence, both the compounds may serve as potential anticancer agents and could be developed as breast cancer drugs, with further explorations. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

ClinicalTrials.gov

2018-03-07

Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

“We both just trusted and leaned on the Lord”: A qualitative study of religiousness and spirituality among African American breast cancer survivors and their caregivers

PubMed Central

Sterba, Katherine Regan; Burris, Jessica L.; Heiney, Sue P.; Ruppel, Megan Baker; Ford, Marvella E.; Zapka, Jane

2014-01-01

Purpose Most breast cancer survivorship research focuses on the general population of survivors. Scant research investigates the potentially unique experiences of minorities, especially during and after the difficult transition from primary treatment to post-treatment. This qualitative study explored African American breast cancer survivors’ and caregivers’ quality-of-life in the post-treatment period with a focus on social and spiritual well-being. Methods Participants included a convenience sample of African American women with stage I-III breast cancer (N=23) who completed treatment 6–24 months before enrollment. Primary caregivers (N=22) included friends, spouses and other family members (21 complete dyads). Participants completed separate semi-structured telephone interviews. Template analysis was used to evaluate themes related to religiousness and spirituality, both across and within dyads. Results After treatment, religiousness and spirituality played a major role in both survivors’ and caregivers’ lives by: 1) providing global guidance, 2) guiding illness management efforts and 3) facilitating recovery. Participants described a spiritual connectedness with God and others in their social networks. Dyad members shared the goal of keeping a positive attitude and described positive growth from cancer. Few future concerns were expressed due to the belief that survivors were healed and “done” with cancer. Beyond practical and emotional support, provision of spiritual assistance was common. Conclusions Results highlight the principal, positive role of religiousness and spirituality for African American breast cancer survivors and caregivers after treatment. Findings emphasize the need to assess the importance of religious and spiritual beliefs and practices, and if appropriate, to provide resources that promote spiritual well-being. PMID:24578149

Quantitative Characterization of Cell Behaviors through Cell Cycle Progression via Automated Cell Tracking

PubMed Central

Wang, Yuliang; Jeong, Younkoo; Jhiang, Sissy M.; Yu, Lianbo; Menq, Chia-Hsiang

2014-01-01

Cell behaviors are reflections of intracellular tension dynamics and play important roles in many cellular processes. In this study, temporal variations in cell geometry and cell motion through cell cycle progression were quantitatively characterized via automated cell tracking for MCF-10A non-transformed breast cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic breast cancer cells. A new cell segmentation method, which combines the threshold method and our modified edge based active contour method, was applied to optimize cell boundary detection for all cells in the field-of-view. An automated cell-tracking program was implemented to conduct live cell tracking over 40 hours for the three cell lines. The cell boundary and location information was measured and aligned with cell cycle progression with constructed cell lineage trees. Cell behaviors were studied in terms of cell geometry and cell motion. For cell geometry, cell area and cell axis ratio were investigated. For cell motion, instantaneous migration speed, cell motion type, as well as cell motion range were analyzed. We applied a cell-based approach that allows us to examine and compare temporal variations of cell behavior along with cell cycle progression at a single cell level. Cell body geometry along with distribution of peripheral protrusion structures appears to be associated with cell motion features. Migration speed together with motion type and motion ranges are required to distinguish the three cell-lines examined. We found that cells dividing or overlapping vertically are unique features of cell malignancy for both MCF-7 and MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together, our live cell tracking system serves as an invaluable tool to identify cell behaviors that are unique to malignant and/or highly metastatic breast cancer cells. PMID:24911281

Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

ClinicalTrials.gov

2017-04-12

Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Stress Test in Detecting Heart Damage in Premenopausal Women With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-04-26

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Premenopausal; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

NASA Technical Reports Server (NTRS)

Yu, Y.; Okayasu, R.; Weil, M. M.; Silver, A.; McCarthy, M.; Zabriskie, R.; Long, S.; Cox, R.; Ullrich, R. L.

2001-01-01

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

PubMed

Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

2016-04-01

Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

ClinicalTrials.gov

2011-12-07

Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

ClinicalTrials.gov

2018-05-01

Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

ClinicalTrials.gov

2017-09-12

Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

ClinicalTrials.gov

2017-02-28

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

ClinicalTrials.gov

2018-02-01

Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Computerized Cognitive Retraining in Improving Cognitive Function in Breast Cancer Survivors

ClinicalTrials.gov

2017-12-11

Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis

PubMed Central

Zhang, Hui; Li, Jiufeng; He, Tianfang; Yeo, Eun-Jin; Soong, Daniel Y.H.; Carragher, Neil O.; Munro, Alison; Chang, Alvin; Bresnick, Anne R.; Lang, Richard A.

2015-01-01

Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, the primary cause of cancer deaths, has been poorly explored. Our previous studies identified a population of metastasis-associated macrophages (MAMs) recruited to the lung that promote tumor cell seeding and growth. Here we show that FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels a subset of macrophages in human breast cancers that are significantly enriched in metastatic sites. In mouse models of breast cancer pulmonary metastasis, MAMs uniquely express FLT1. Using several genetic models, we show that macrophage FLT1 signaling is critical for metastasis. FLT1 inhibition does not affect MAM recruitment to metastatic lesions but regulates a set of inflammatory response genes, including colony-stimulating factor 1 (CSF1), a central regulator of macrophage biology. Using a gain-of-function approach, we show that CSF1-mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity of FLT1-inhibited MAMs. Thus, CSF1 is epistatic to FLT1, establishing a link between FLT1 and inflammatory responses within breast tumor metastases. Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease. PMID:26261265

Integrated Immunotherapy for Breast Cancer

DTIC Science & Technology

2013-09-01

that promotes appropriate cellular signals. For example, recent studies by Mohtashami et al have shown that expression of two critical Notch ligands...aggregate analysis for DC populations is identified in other tumors/cancers (10). We also have begun banking tumor associated stromal RNA , healthy stromal... RNA , as well as tumor RNA for future analysis on microarray or RNAseq to identify unique markers which may be influencing DC clustering or maturation

Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

ClinicalTrials.gov

2016-06-20

Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families.

PubMed

Reeves, Michelle D; Yawitch, Tali M; van der Merwe, Nerina C; van den Berg, Hester J; Dreyer, Greta; van Rensburg, Elizabeth J

2004-07-10

Germ-line mutations within BRCA1 are responsible for different proportions of inherited susceptibility to breast/ovarian cancer, and the spectrum of mutations within this gene is often unique to certain populations. At this time, there have been no reports regarding the role of BRCA1 in South African breast and/or ovarian cancer families. We therefore screened 90 South African breast/ovarian cancer families for BRCA1 mutations by means of PCR-based mutation detection assays. Eighteen families (20%) were identified with BRCA1 disease-causing mutations. Four Ashkenazi Jewish families were identified with the 185delAG mutation, whereas 2 Afrikaner and 1 Ashkenazi Jewish family were found to harbor the 5382insC mutation. Five of the families (5.56%), all of whom are Afrikaners, were found to carry the novel E881X mutation. Genotype analyses show that these patients share a common ancestor. Genealogic studies have identified 3 possible founding couples for this mutation, all of whom arrived in the Cape from France in the late 1600s. Of the remaining mutations detected, 3 have not been reported previously and include the S451X, 1493delC (detected twice) and 4957insC mutations. Copyright 2004 Wiley-Liss, Inc.

Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

ClinicalTrials.gov

2018-03-15

HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

ClinicalTrials.gov

2018-01-11

Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients.

PubMed

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-06-01

Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37°C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-06-27

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

ClinicalTrials.gov

2018-01-04

Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

ClinicalTrials.gov

2018-02-15

Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

ClinicalTrials.gov

2017-08-08

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Virtual Weight Loss Program in Maintaining Weight in African American Breast Cancer Survivors

ClinicalTrials.gov

2018-06-13

Cancer Survivor; Invasive Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

ClinicalTrials.gov

2018-05-11

Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery

ClinicalTrials.gov

2018-02-12

Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer

Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer

ClinicalTrials.gov

2017-11-15

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth.

PubMed

Chen, Jun; Kinoshita, Taisei; Sukbuntherng, Juthamas; Chang, Betty Y; Elias, Laurence

2016-12-01

Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nmol/L); in addition, the IC 50 s were lower than that of lapatinib and dacomitinib. Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK. Irreversible inhibition of HER2 and EGFR in breast cancer cells was established after 30-minute incubation above 100 nmol/L or following 2-hour incubation at lower concentrations. Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction. The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK. Xenograft studies with HER2 + MDA-MB-453 and BT-474 cells in mice in conjunction with determination of pharmacokinetics demonstrated significant exposure-dependent inhibition of growth and key signaling molecules at levels that are clinically achievable. Ibrutinib's unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology. Mol Cancer Ther; 15(12); 2835-44. ©2016 AACR. ©2016 American Association for Cancer Research.

The effects of combined selenium nanoparticles and radiation therapy on breast cancer cells in vitro.

PubMed

Chen, Feng; Zhang, Xiao Hong; Hu, Xiao Dan; Liu, Pei Dang; Zhang, Hai Qian

2018-08-01

Radiosensitizers that increase cancer cell radio-sensitivity can enhance the effectiveness of irradiation and minimize collateral damage. Nanomaterial has been employed in conjunction with radiotherapy as radiosensitizers, due to its unique physicochemical properties. In this article, we evaluated selenium nanoparticles (Nano-Se) as a new radiosensitizer. Nano-Se was used in conjunction with irradiation on MCF-7 breast cancer cells, and efficacy and mechanisms of this combined treatment approach were evaluated. Nano-Se reinforced the toxic effects of irradiation, leading to a higher mortality rate than either treatment used alone, inducing cell cycle arrest at the G2/M phase and the activation of autophagy, and increasing both endogenous and irradiation-induced reactive oxygen species formation. These results suggest that Nano-Se can be used as an adjuvant drug to improve cancer cell sensitivity to the toxic effects of irradiation and thereby reduce damage to normal tissue nearby.

Questionnaires in Identifying Upper Extremity Function and Quality of Life After Treatment in Patients With Breast Cancer

ClinicalTrials.gov

2017-04-11

Musculoskeletal Complication; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-Related Toxicity

Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-06-25

Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Comparison of Reconstructive Outcomes in Breast Cancer Patients With Preexisting Subpectoral Implants: Implant-Sparing Mastectomy With Delayed Implant Exchange Versus Immediate Tissue Expander Reconstruction.

PubMed

Parabkaharan, Sangeetha; Melody, Megan; Trotta, Rose; Lleshi, Amina; Sun, Weihong; Smith, Paul D; Khakpour, Nazanin; Dayicioglu, Deniz

2016-06-01

Women who have undergone prior augmentation mammoplasty represent a unique subset of breast cancer patients with several options available for breast reconstruction. We performed a single institution review of surgical outcomes of breast reconstruction performed in patients with breast cancer with prior history of subpectoral breast augmentation. Institutional review board-approved retrospective review was conducted among patients with previously mentioned criteria treated at our institution between 2000 and 2014. Reconstructions were grouped into 2 categories as follows: (1) removal of preexisting subpectoral implant during mastectomy with immediate tissue expander placement and (2) implant-sparing mastectomy followed by delayed exchange to a larger implant. We reviewed demographics, tumor features, and reconstruction outcomes of these groups. Fifty-three patients had preexisting subpectoral implants. Of the 63 breast reconstructions performed, 18 (28.6%) had immediate tissue expander placed and 45 (71.4%) had implant-sparing mastectomy followed by delayed implant exchange. The groups were comparable based on age, body mass index, cancer type, tumor grade, TNM stage at presentation, and hormonal receptor status. No significant difference was noted between tumor margins or subsequent recurrence, mastectomy specimen weight, removed implant volume, volume of implant placed during reconstruction, or time from mastectomy to final implant placement. Rates of complications were significantly higher in the tissue expander group compared to the implant-sparing mastectomy group 7 (38.9%) versus 4 (8.9%) (P = 0.005). Implant-sparing mastectomy with delayed implant exchange in patients with preexisting subpectoral implants is safe and has fewer complications compared to tissue expander placement. There was no difference noted in the final volume of implant placed, time interval for final implant placement, or tumor margins.

A Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)

ClinicalTrials.gov

2015-05-07

Estrogen Receptor-positive Breast Cancer; Musculoskeletal Complications; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

ClinicalTrials.gov

2017-08-30

Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

ClinicalTrials.gov

2018-06-08

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer

PubMed Central

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures. PMID:29596496

The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer.

PubMed

Bai, Fang; Morcos, Faruck; Sohn, Yang-Sung; Darash-Yahana, Merav; Rezende, Celso O; Lipper, Colin H; Paddock, Mark L; Song, Luhua; Luo, Yuting; Holt, Sarah H; Tamir, Sagi; Theodorakis, Emmanuel A; Jennings, Patricia A; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel

2015-03-24

Identification of novel drug targets and chemotherapeutic agents is a high priority in the fight against cancer. Here, we report that MAD-28, a designed cluvenone (CLV) derivative, binds to and destabilizes two members of a unique class of mitochondrial and endoplasmic reticulum (ER) 2Fe-2S proteins, mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1), recently implicated in cancer cell proliferation. Docking analysis of MAD-28 to mNT/NAF-1 revealed that in contrast to CLV, which formed a hydrogen bond network that stabilized the 2Fe-2S clusters of these proteins, MAD-28 broke the coordinative bond between the His ligand and the cluster's Fe of mNT/NAF-1. Analysis of MAD-28 performed with control (Michigan Cancer Foundation; MCF-10A) and malignant (M.D. Anderson-metastatic breast; MDA-MB-231 or MCF-7) human epithelial breast cells revealed that MAD-28 had a high specificity in the selective killing of cancer cells, without any apparent effects on normal breast cells. MAD-28 was found to target the mitochondria of cancer cells and displayed a surprising similarity in its effects to the effects of mNT/NAF-1 shRNA suppression in cancer cells, causing a decrease in respiration and mitochondrial membrane potential, as well as an increase in mitochondrial iron content and glycolysis. As expected, if the NEET proteins are targets of MAD-28, cancer cells with suppressed levels of NAF-1 or mNT were less susceptible to the drug. Taken together, our results suggest that NEET proteins are a novel class of drug targets in the chemotherapeutic treatment of breast cancer, and that MAD-28 can now be used as a template for rational drug design for NEET Fe-S cluster-destabilizing anticancer drugs.

Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

ClinicalTrials.gov

2018-05-30

Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Development of a questionnaire encompassing indicators of distress: a tool for use with women in surgical continuity of care for breast cancer.

PubMed

Jørgensen, L; Garne, J P; Søgaard, M; Laursen, B S

2015-04-01

Women with breast cancer often experience significant distress. Currently, there are no questionnaires aimed at identifying women's unique and possible changing indicators for distress in surgical continuity of care for breast cancer. We developed and tested three questionnaires specifically for this use. We first searched PubMed, CINAHL and PsycINFO to retrieve information on previously described indicators. Next, we conducted a focus group interview with 6 specialised nurses, who have extensive experience about consequences of breast cancer for women in surgical continuity of care. The questionnaire was tested on 18 women scheduled for breast cancer surgery. Subsequently, the women were debriefed to gain knowledge about comprehensibility, readability and relevance of items, and the time needed to complete the questionnaire. After adjustment, the questionnaires were field-tested concomitantly with a clinical study, which both consisted of a survey and an interview study. Three multi-item questionnaires were developed specific to different time points in surgical continuity of care. The questionnaires share a core of statements divided into seven sub-scales: emotional and physical situation, social condition, sexuality, body image, religion and organisational factors. Besides the core of statements, each questionnaire has different statements depending on the time point of surgical continuity of care when it was to be responded to. The questionnaires contain comprehensive items that can identify indicators for distress in individual women taking part in surgical continuity of care. The items were understandable and the time used for filling in the questionnaires was reasonable. Copyright © 2014 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Xu-Qian; Liu, Xiang-Fan; Yao, Ling

Highlights: •A novel FAK splicing mutation identified in breast tumor. •FAK-Del33 mutation promotes cell migration and invasion. •FAK-Del33 mutation regulates FAK/Src signal pathway. -- Abstract: Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introducedmore » into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.« less

Phase II Study of Everolimus Beyond Progression

ClinicalTrials.gov

2017-09-29

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly

PubMed Central

Lin, Xiaoti; Chen, Weiyu; Wei, Fengqin; Zhou, Binhua P.; Hung, Mien-Chie; Xie, Xiaoming

2017-01-01

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning protocol. Tissue microarray analysis has been used to study 217 cases of clinical breast cancer specimens. Results: Here, we have successfully established four long-term maintenance BCSC that retain their tumor-initiating biological properties. Our analyses of microarray and qRT-PCR explored that miR-34a is the most pronounced microRNA for investigation of BCSC. We establish hTERT promoter-driven VISA delivery of miR-34a (TV-miR-34a) plasmid that can induce high throughput of miR-34a expression in BCSC. TV-miR-34a significantly inhibited the tumor-initiating properties of long-term-cultured BCSC in vitro and reduced the proliferation of BCSC in vivo by an efficient and safe way. TV-miR-34a synergizes with docetaxel, a standard therapy for invasive breast cancer, to act as a BCSC inhibitor. Further mechanistic investigation indicates that TV-miR-34a directly prevents C22ORF28 accumulation, which abrogates clonogenicity and tumor growth and correlates with low miR-34 and high C22ORF28 levels in breast cancer patients. Conclusion: Taken together, we generated four long-term maintenance BCSC derived from either clinical specimens or cell lines, which would be greatly beneficial to the research progress in breast cancer patients. We further developed the non-viral TV-miR-34a plasmid, which has a great potential to be applied as a clinical application for breast cancer therapy. PMID:29187905

Breast cancer in Asian Americans in California, 1988-2013: increasing incidence trends and recent data on breast cancer subtypes.

PubMed

Gomez, Scarlett Lin; Von Behren, Julie; McKinley, Meg; Clarke, Christina A; Shariff-Marco, Salma; Cheng, Iona; Reynolds, Peggy; Glaser, Sally L

2017-07-01

In contrast to other US racial/ethnic groups, Asian Americans (AA) have experienced steadily increasing breast cancer rates in recent decades. To better understand potential contributors to this increase, we examined incidence trends by age and stage among women from seven AA ethnic groups in California from 1988 to 2013, and incidence patterns by subtype and age at diagnosis for the years 2009 through 2013. Joinpoint regression was applied to California Cancer Registry data to calculate annual percentage change (APC) for incidence trends. Incidence rate ratios were used to compare rates for AA ethnic groups relative to non-Hispanic whites (NHW). All AA groups except Japanese experienced incidence increases, with the largest among Koreans in 1988-2006 (APC 4.7, 95% CI 3.8, 5.7) and Southeast Asians in 1988-2013 (APC 2.5, 95% CI 0.8, 4.2). Among women younger than age 50, large increases occurred for Vietnamese and other Southeast Asians; among women over age 50, increasing trends occurred in all AA ethnic groups. Rates increased for distant-stage disease among Filipinas (2.2% per year, 95% CI 0.4, 3.9). Compared to NHW, Filipinas and older Vietnamese had higher incidence rates of some HER2+ subtypes. Breast cancer incidence rates have risen rapidly among California AA, with the greatest increases in Koreans and Southeast Asians. Culturally tailored efforts to increase awareness of and attention to breast cancer risk factors are needed. Given the relatively higher rates of HER2-overexpressing subtypes in some AA ethnicities, research including these groups and their potentially unique exposures may help elucidate disease etiology.

A glucose-targeted mixed micellar formulation outperforms Genexol in breast cancer cells.

PubMed

Moretton, Marcela A; Bernabeu, Ezequiel; Grotz, Estefanía; Gonzalez, Lorena; Zubillaga, Marcela; Chiappetta, Diego A

2017-05-01

Breast cancer represents the top cancer among women, accounting 521.000 deaths per year. Development of targeted nanomedicines to breast cancer tissues represents a milestone to reduce chemotherapy side effects. Taking advantage of the over-expression of glucose (Glu) membrane transporters in breast cancer cells, we aim to expand the potential of a paclitaxel (PTX)-loaded mixed micellar formulation based on polyvinyl caprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by its surface decoration with Glu moieties. The glycopolymer (Soluplus(Glu)) was obtained by microwave-assisted ring opening reaction of δ-gluconolactone initiated by Soluplus®. The glycosylation was confirmed by 1 H NMR and by agglutination assays employing Concanavalin A. The hydrodynamic diameter of Soluplus(Glu) micelles was characterized by dynamic light scattering (100.3±3.8nm) as well as the critical micellar concentration value (0.0151% w/v). Then, a mixed micelle formulation employing Soluplus®, Soluplus(Glu) and TPGS (3:1:1wt ratio) loaded with PTX (4mg/mL) was developed as a multifunctional nanocarrier. Its in vitro anticancer performance in MCF-7 (1.6-fold) and MDA-MB-231 (14.1-fold) was significantly enhanced (p<0.05) versus the unique commercially available micellar-based PTX-nanoformulation (Genexol®). Furthermore, the in vitro PTX cellular uptake assays revealed that the drug intracellular/cell content was significantly (p<0.05) higher for the Glu-containing mixed micelles versus Genexol® after 6h of incubation with MCF-7 (30.5-fold) and MDA-MB-231 (5-fold). Overall, results confirmed the potential of our Glu-decorated mixed colloidal formulation as an intelligent nanocarrier for PTX-targeted breast cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast cancer treatment across health care systems: linking electronic medical records and state registry data to enable outcomes research.

PubMed

Kurian, Allison W; Mitani, Aya; Desai, Manisha; Yu, Peter P; Seto, Tina; Weber, Susan C; Olson, Cliff; Kenkare, Pragati; Gomez, Scarlett L; de Bruin, Monique A; Horst, Kathleen; Belkora, Jeffrey; May, Suepattra G; Frosch, Dominick L; Blayney, Douglas W; Luft, Harold S; Das, Amar K

2014-01-01

Understanding of cancer outcomes is limited by data fragmentation. In the current study, the authors analyzed the information yielded by integrating breast cancer data from 3 sources: electronic medical records (EMRs) from 2 health care systems and the state registry. Diagnostic test and treatment data were extracted from the EMRs of all patients with breast cancer treated between 2000 and 2010 in 2 independent California institutions: a community-based practice (Palo Alto Medical Foundation; "Community") and an academic medical center (Stanford University; "University"). The authors incorporated records from the population-based California Cancer Registry and then linked EMR-California Cancer Registry data sets of Community and University patients. The authors initially identified 8210 University patients and 5770 Community patients; linked data sets revealed a 16% patient overlap, yielding 12,109 unique patients. The percentage of all Community patients, but not University patients, treated at both institutions increased with worsening cancer prognostic factors. Before linking the data sets, Community patients appeared to receive less intervention than University patients (mastectomy: 37.6% vs 43.2%; chemotherapy: 35% vs 41.7%; magnetic resonance imaging: 10% vs 29.3%; and genetic testing: 2.5% vs 9.2%). Linked Community and University data sets revealed that patients treated at both institutions received substantially more interventions (mastectomy: 55.8%; chemotherapy: 47.2%; magnetic resonance imaging: 38.9%; and genetic testing: 10.9% [P < .001 for each 3-way institutional comparison]). Data linkage identified 16% of patients who were treated in 2 health care systems and who, despite comparable prognostic factors, received far more intensive treatment than others. By integrating complementary data from EMRs and population-based registries, a more comprehensive understanding of breast cancer care and factors that drive treatment use was obtained. © 2013 American Cancer Society.

The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells

PubMed Central

Zamberi, Nur Rizi; Abu, Nadiah; Mohamed, Nurul Elyani; Nordin, Noraini; Keong, Yeap Swee; Beh, Boon Kee; Zakaria, Zuki Abu Bakar; Nik Abdul Rahman, Nik Mohd Afizan; Alitheen, Noorjahan Banu

2016-01-01

Background. Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. Methods. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Results. Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water–treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water–treated group. Conclusions. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment. PMID:27230756

The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells.

PubMed

Zamberi, Nur Rizi; Abu, Nadiah; Mohamed, Nurul Elyani; Nordin, Noraini; Keong, Yeap Swee; Beh, Boon Kee; Zakaria, Zuki Abu Bakar; Nik Abdul Rahman, Nik Mohd Afizan; Alitheen, Noorjahan Banu

2016-12-01

Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Kefir water was cytotoxic toward 4T1 cells at IC 50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water-treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water-treated group. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment. © The Author(s) 2016.

Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

ClinicalTrials.gov

2016-10-11

Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer.

PubMed

Monnier, Alain M

2007-05-01

As there is a risk for relapse in early breast cancer, especially at 1-3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the optimal treatment strategy (i.e., initial adjuvant aromatase inhibitor therapy or sequential adjuvant aromatase inhibitor therapy).

Vascular and Cognitive Assessments in Patients With Breast Cancer Undergoing Chemotherapy After Surgery

ClinicalTrials.gov

2017-05-25

Cognitive/Functional Effects; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Rosuvastatin in Treating Women With Cardiovascular Complications Who Are Undergoing Chemotherapy For Breast Cancer

ClinicalTrials.gov

2017-05-25

Cardiovascular Complications; Recurrent Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Challenges in Recruiting Aging Women Holocaust Survivors to a Case Control Study of Breast Cancer.

PubMed

Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

2015-01-01

Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel. Copyright 2015, SLACK Incorporated.

Cryotherapy in Preventing Peripheral Neuropathy and Nail Toxicity in Patients With Breast Cancer Who Are Receiving Paclitaxel

ClinicalTrials.gov

2018-01-09

Chemotherapeutic Agent Toxicity; Pain; Peripheral Neuropathy; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-related Toxicity

Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-18

Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Post-treatment problems of African American breast cancer survivors.

PubMed

Barsevick, Andrea M; Leader, Amy; Bradley, Patricia K; Avery, Tiffany; Dean, Lorraine T; DiCarlo, Melissa; Hegarty, Sarah E

2016-12-01

African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems. A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems. Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems. The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.

Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

ClinicalTrials.gov

2018-01-29

Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-06-28

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

Using Twitter for breast cancer prevention: an analysis of breast cancer awareness month

PubMed Central

2013-01-01

Background One in eight women will develop breast cancer in her lifetime. The best-known awareness event is breast cancer awareness month (BCAM). BCAM month outreach efforts have been associated with increased media coverage, screening mammography and online information searching. Traditional mass media coverage has been enhanced by social media. However, there is a dearth of literature about how social media is used during awareness-related events. The purpose of this research was to understand how Twitter is being used during BCAM. Methods This was a cross-sectional, descriptive study. We collected breast cancer- related tweets from 26 September - 12 November 2012, using Twitter’s application programming interface. We classified Twitter users into organizations, individuals, and celebrities; each tweet was classified as an original or a retweet, and inclusion of a mention, meaning a reference to another Twitter user with @username. Statistical methods included ANOVA and chi square. For content analysis, we used computational linguistics techniques, specifically the MALLET implementation of the unsupervised topic modeling algorithm Latent Dirichlet Allocation. Results There were 1,351,823 tweets by 797,827 unique users. Tweets spiked dramatically the first few days then tapered off. There was an average of 1.69 tweets per user. The majority of users were individuals. Nearly all of the tweets were original. Organizations and celebrities posted more often than individuals. On average celebrities made far more impressions; they were also retweeted more often and their tweets were more likely to include mentions. Individuals were more likely to direct a tweet to a specific person. Organizations and celebrities emphasized fundraisers, early detection, and diagnoses while individuals tweeted about wearing pink. Conclusions Tweeting about breast cancer was a singular event. The majority of tweets did not promote any specific preventive behavior. Twitter is being used mostly as a one-way communication tool. To expand the reach of the message and maximize the potential for word-of-mouth marketing using Twitter, organizations need a strategic communications plan to ensure on-going social media conversations. Organizations may consider collaborating with individuals and celebrities in these conversations. Social media communication strategies that emphasize fundraising for breast cancer research seem particularly appropriate. PMID:24168075

Using Twitter for breast cancer prevention: an analysis of breast cancer awareness month.

PubMed

Thackeray, Rosemary; Burton, Scott H; Giraud-Carrier, Christophe; Rollins, Stephen; Draper, Catherine R

2013-10-29

One in eight women will develop breast cancer in her lifetime. The best-known awareness event is breast cancer awareness month (BCAM). BCAM month outreach efforts have been associated with increased media coverage, screening mammography and online information searching. Traditional mass media coverage has been enhanced by social media. However, there is a dearth of literature about how social media is used during awareness-related events. The purpose of this research was to understand how Twitter is being used during BCAM. This was a cross-sectional, descriptive study. We collected breast cancer- related tweets from 26 September - 12 November 2012, using Twitter's application programming interface. We classified Twitter users into organizations, individuals, and celebrities; each tweet was classified as an original or a retweet, and inclusion of a mention, meaning a reference to another Twitter user with @username. Statistical methods included ANOVA and chi square. For content analysis, we used computational linguistics techniques, specifically the MALLET implementation of the unsupervised topic modeling algorithm Latent Dirichlet Allocation. There were 1,351,823 tweets by 797,827 unique users. Tweets spiked dramatically the first few days then tapered off. There was an average of 1.69 tweets per user. The majority of users were individuals. Nearly all of the tweets were original. Organizations and celebrities posted more often than individuals. On average celebrities made far more impressions; they were also retweeted more often and their tweets were more likely to include mentions. Individuals were more likely to direct a tweet to a specific person. Organizations and celebrities emphasized fundraisers, early detection, and diagnoses while individuals tweeted about wearing pink. Tweeting about breast cancer was a singular event. The majority of tweets did not promote any specific preventive behavior. Twitter is being used mostly as a one-way communication tool. To expand the reach of the message and maximize the potential for word-of-mouth marketing using Twitter, organizations need a strategic communications plan to ensure on-going social media conversations. Organizations may consider collaborating with individuals and celebrities in these conversations. Social media communication strategies that emphasize fundraising for breast cancer research seem particularly appropriate.

Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2014-04-02

Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

ClinicalTrials.gov

2016-12-09

Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

ClinicalTrials.gov

2017-06-14

Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

ClinicalTrials.gov

2017-08-07

Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2017-11-15

Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

Phase I: At-Home Support for Rural Women Using Group Video Calling

ClinicalTrials.gov

2014-10-15

Depression; Post-traumatic Stress Disorder; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Educational Counseling in Improving Communication and Quality of Life in Spouses and Breast Cancer Patients

ClinicalTrials.gov

2018-02-06

Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Psychosocial Effects of Cancer and Its Treatment; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission

ClinicalTrials.gov

2017-12-07

HER2/Neu Negative; No Evidence of Disease; One or More Positive Axillary Nodes; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

ClinicalTrials.gov

2017-12-07

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

ClinicalTrials.gov

2018-06-01

Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca

ClinicalTrials.gov

2018-04-17

Breast Adenocarcinoma; Estrogen Receptor- Negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive Tumor; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Triple-negative Breast Carcinoma

Carevive Survivor Care Planning System in Improving Quality of Life in Breast Cancer Survivors

ClinicalTrials.gov

2018-02-20

Stage I Breast Cancer; Stage I Cervical Cancer; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage IA Breast Cancer; Stage IA Cervical Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Cervical Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Breast Cancer; Stage II Cervical Cancer; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Cervical Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Cervical Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Ovarian Cancer; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Uterine Corpus Cancer

FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

ClinicalTrials.gov

2018-04-13

Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

ClinicalTrials.gov

2017-03-29

Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

Racial and Ethnic Disparities in Patient-Provider Communication With Breast Cancer Patients: Evidence From 2011 MEPS and Experiences With Cancer Supplement

PubMed Central

White-Means, Shelley I.; Osmani, Ahmad Reshad

2017-01-01

The current study explores racial/ethnic disparities in the quality of patient-provider communication during treatment, among breast cancer patients. A unique data set, Medical Expenditure Panel Survey and Experiences With Cancer Supplement 2011, is used to examine this topic. Using measures of the quality of patient-provider communication that patients are best qualified to evaluate, we explore the relationship between race/ethnicity and patients’ perspectives on whether (1) patient-provider interactions are respectful, (2) providers are listening to patients, (3) providers provide adequate explanations of outcomes and treatment, and (4) providers spend adequate time in interacting with the patients. We also examine the relationship between race/ethnicity and patients’ perspectives on whether their (1) doctor ever discussed need for regular follow-up care and monitoring after completing treatment, (2) doctor ever discussed long-term side effects of cancer treatment, (3) doctor ever discussed emotional or social needs related to cancer, and (4) doctor ever discussed lifestyle or health recommendations. Multivariate ordinary least squares and ordered logistic regression models indicate that after controlling for factors such as income and health insurance coverage, the quality of patient-provider communication with breast cancer patients varies by race/ethnicity. Non-Hispanic blacks experience the greatest communication deficit. Our findings can inform the content of future strategies to reduce disparities. PMID:28856941

Denosumab as an add-on Neoadjuvant Treatment (GeparX)

ClinicalTrials.gov

2017-07-10

Breast Cancer Female NOS; Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Invasive Ductal Breast Cancer; HER2 Positive Breast Cancer; Inflammatory Breast Cancer; Tubular Breast Cancer Stage III

MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

ClinicalTrials.gov

2017-08-01

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer

ClinicalTrials.gov

2017-10-10

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2016-09-21

Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

ClinicalTrials.gov

2018-05-04

Inflammatory Breast Cancer; Stage IIA Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer; Stage IIB Breast Cancer; Estrogen Receptor Negative; Progesterone Receptor Negative; HER2/Neu Negative

A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)

ClinicalTrials.gov

2017-07-10

Tubular Breast Cancer Stage II; Tubular Breast Cancer Stage III; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; HER2 Positive Breast Cancer; Inflammatory Breast Cancer

Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

ClinicalTrials.gov

2017-10-05

Ductal Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

ClinicalTrials.gov

2018-06-18

Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

Measuring preparedness for mammography in women with intellectual disabilities: a validation study of the Mammography Preparedness Measure.

PubMed

Wang, Claire Tienwey; Greenwood, Nechama; White, Laura F; Wilkinson, Joanne

2015-05-01

Women with intellectual disabilities have similar breast cancer rates as the general population, but lower rates of regular mammography and higher breast cancer mortality rates. Although prior qualitative work demonstrates that women with intellectual disabilities face unique, disability-specific barriers to mammography, the present authors lack standardized, validated instruments for measuring knowledge of breast cancer screening in this population. In addition, much research related to adults with intellectual disabilities focuses on family or carer perspectives, rather than involving women with intellectual disabilities, themselves. The present authors first pilot tested a general population instrument measuring breast cancer knowledge, and found that it did not perform adequately in women with intellectual disabilities. In response, the present authors developed the Mammography Preparedness Measure (MPM), a direct short interview tool to measure knowledge and preparedness in women with intellectual disabilities, themselves, rather than relying on caregiver or other reports, and using inclusive methodology. The present authors validated the MPM by assessing test-retest reliability. Average test-retest per cent agreement of 84%, ranging from 74 to 91% agreement per item, with an overall kappa of 0.59. The MPM appears to be a valid instrument appropriate for measuring mammography preparedness in women with intellectual disabilities. The success of this innovative tool suggests that direct, rather than informant-directed tools can be developed to measure health knowledge and cancer screening readiness in adults with intellectual disabilities, an important measure in studying and reducing disparities. © 2014 John Wiley & Sons Ltd.

Pazopanib Inhibits the Activation of PDGFRβ-Expressing Astrocytes in the Brain Metastatic Microenvironment of Breast Cancer Cells

PubMed Central

Gril, Brunilde; Palmieri, Diane; Qian, Yongzhen; Anwar, Talha; Liewehr, David J.; Steinberg, Seth M.; Andreu, Zoraida; Masana, Daniel; Fernández, Paloma; Steeg, Patricia S.; Vidal-Vanaclocha, Fernando

2014-01-01

Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor β (at tyrosine 751; p751-PDGFRβ) was identified around perivascular brain micrometastases. p751-PDGFRβ+ astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRβ+ astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients. PMID:23583652

Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer.

PubMed

Giamas, Georgios; Filipović, Aleksandra; Jacob, Jimmy; Messier, Walter; Zhang, Hua; Yang, Dongyun; Zhang, Wu; Shifa, Belul Assefa; Photiou, Andrew; Tralau-Stewart, Cathy; Castellano, Leandro; Green, Andrew R; Coombes, R Charles; Ellis, Ian O; Ali, Simak; Lenz, Heinz-Josef; Stebbing, Justin

2011-06-01

Therapies targeting estrogen receptor α (ERα, encoded by ESR1) have transformed the treatment of breast cancer. However, large numbers of women relapse, highlighting the need for the discovery of new regulatory targets modulating ERα pathways. An siRNA screen identified kinases whose silencing alters the estrogen response including those previously implicated in regulating ERα activity (such as mitogen-activated protein kinase and AKT). Among the most potent regulators was lemur tyrosine kinase-3 (LMTK3), for which a role has not previously been assigned. In contrast to other modulators of ERα activity, LMTK3 seems to have been subject to Darwinian positive selection, a noteworthy result given the unique susceptibility of humans to ERα+ breast cancer. LMTK3 acts by decreasing the activity of protein kinase C (PKC) and the phosphorylation of AKT (Ser473), thereby increasing binding of forkhead box O3 (FOXO3) to the ESR1 promoter. LMTK3 phosphorylated ERα, protecting it from proteasomal degradation in vitro. Silencing of LMTK3 reduced tumor volume in an orthotopic mouse model and abrogated proliferation of ERα+ but not ERα- cells, indicative of its role in ERα activity. In human cancers, LMTK3 abundance and intronic polymorphisms were significantly associated with disease-free and overall survival and predicted response to endocrine therapies. These findings yield insights into the natural history of breast cancer in humans and reveal LMTK3 as a new therapeutic target.

Kindness Interventions in Enhancing Well-Being in Breast Cancer Survivors

ClinicalTrials.gov

2018-06-18

Cancer Survivor; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2017-07-28

Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

ClinicalTrials.gov

2018-03-02

Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

ClinicalTrials.gov

2018-06-08

Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

Breast cancer health promotion in Qatar: a survey of community pharmacists' interests and needs.

PubMed

El Hajj, Maguy Saffouh; Hamid, Yousra

2013-06-01

Breast cancer is the most common cancer in women in Qatar. Despite the sustained efforts to increase breast cancer public awareness via campaigns and public screening programmes, breast cancer screening rate remains low. The involvement of community pharmacists in the communication and distribution of breast cancer screening information should have a significant positive impact. The objectives of this study were to determine the degree of community pharmacists' involvement in breast cancer health promotion activities in Qatar, to explore their attitudes towards the involvement in breast cancer health promotion, to assess their breast cancer knowledge, to gauge their interest in receiving breast cancer continuous education and to list their perceived barriers for including breast cancer health promotion activities into their daily practice. Community pharmacies in Qatar. The study objectives were addressed in a cross-sectional survey of all community pharmacists in Qatar. The extent of community pharmacists' involvement in breast cancer health promotion activities, the community pharmacists' interest and comfort in providing breast cancer health promotion, their breast cancer knowledge, their interest in receiving breast cancer continuous education, their attitudes and beliefs towards breast cancer health promotion and their perceived barriers for integrating breast cancer heath promotion activities into their daily practice. Over a 12-week period, we collected 195 surveys (60% response rate). Eighty-eight percent indicated that they never invited healthcare professionals to provide breast cancer education in the pharmacy, 78% said that they never distributed breast cancer educational materials, and 58% reported that they never counseled patients about breast cancer. Nevertheless, more than 60% were highly interested in being engaged in breast cancer health promotion activities. In addition, 87% believed that discussing breast cancer awareness with female patients in the pharmacy was beneficial to patients. Yet pharmacists perceived many barriers for integrating breast cancer health promotion into their daily practice including lack of educational materials (79%) and lack of public recognition (61%). Moreover, their breast cancer knowledge mean score was 63% with 77% expressing a high interest in receiving breast cancer continuous education. Despite their low involvement in breast cancer health promotion, the majority of pharmacists were interested in educating patients about breast cancer. However, low breast cancer knowledge and other barriers can prevent actualizing this role. Further work should focus on providing these pharmacists with breast cancer continuous education and overcoming all stated barriers.

Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus

ClinicalTrials.gov

2018-04-26

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Oral Complications; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

ClinicalTrials.gov

2016-07-29

Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Development of chitosan graft pluronic®F127 copolymer nanoparticles containing DNA aptamer for paclitaxel delivery to treat breast cancer cells

NASA Astrophysics Data System (ADS)

Thach Nguyen, Kim; Le, Duc Vinh; Do, Dinh Ho; Huan Le, Quang

2016-06-01

HER-2/ErbB2/Neu(HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves a therapeutic target for breast cancer. In this study, we aimed to isolate DNA aptamer (Ap) that specifically bind to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. We developed a novel multifunctional composite micelle with surface modification of Ap for targeted delivery of paclitaxel. This binary mixed system consisting of Ap modified pluronic®F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Polymeric micelles had a spherical shape and were self-assemblies of block copolymers of approximately 86.22 ± 1.45 nm diameter. PTX could be loaded with high encapsulation efficiency (83.28 ± 0.13%) and loading capacity (9.12 ± 0.34%). The release profile were 29%-35% in the first 12 h and 85%-93% after 12 d at pH 7.5 of receiving media. The IC50 doses by MTT assay showed the greater activity of nanoparticles loaded paclitaxel over free paclitaxel and killed cells up to 95% after 6 h. These results demonstrated unique assembly with the capacity to function as an efficient detection and delivery vehicle in the biological living system.

Margins: a status report from the Annual Meeting of the American Society of Breast Surgeons.

PubMed

Harness, Jay K; Giuliano, Armando E; Pockaj, Barbara A; Downs-Kelly, Erinn

2014-10-01

Since the emergence of breast conserving surgery (BCS) as an alternative to mastectomy in the 1980's, there has been little consensus on what constitutes acceptable margins for cases of invasive breast cancer, how best to evaluate margins in the operating room, or an understanding of the challenging process of margin assessment by pathologists. The program committee for the 15th Annual Meeting of The American Society of Breast Surgeons organized a plenary session to discuss the latest thinking and guidelines for these important issues. The SSO/ASTRO Consensus Guideline on Margins for BCS was an important focus of discussion. The SSO/ASTRO consensus panelists concluded that "no ink on tumor" is an adequate surgical margin for BCS in patients with invasive breast cancers. Intraoperative strategies to decrease the incidence of positive margins include intraoperative localization techniques (wire-localization, ultrasound, radioactive seed) and intraoperative margin assessments with specimen radiography, imprint cytology, and frozen section. Studies also demonstrate the positive effect of shave margins with or without intraoperative margin assessment. The College of American Pathologists protocols for breast specimen margin evaluation consider multiple variables that can impact the proper assessment of margins. These variables include: tissue fixation time, specimen orientation, cold ischemia time, leaking ink, specimen pancaking and others that surgeons need to be aware of. Determining when "enough is enough" should not only be the application of guidelines and national standards, but also a multidisciplinary discussion between breast cancer specialists for what is right for the individual patient's unique circumstances.

Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery

ClinicalTrials.gov

2017-10-02

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Triple-negative Breast Cancer

Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer

ClinicalTrials.gov

2017-12-18

Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Risks of Breast Cancer Screening

MedlinePlus

... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Go ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

Breast cancer in young women.

PubMed

Radecka, Barbara; Litwiniuk, Maria

2016-01-01

Breast cancer (BC) in young women is rare, affecting only 4-6% of women under the age of 40. Regardless, BC remains the most common malignancy among younger patients. Recently, a significant increase in BC rates has been observed among pre-menopausal subjects. Breast cancer in young women requires special attention due to its specific morphologic and prognostic characteristics and unique aspects, including fertility preservation and psychosocial issues (e.g. its impact on family life and career). Young women are more likely to have tumors with higher incidence of negative clinicopathologic features (higher histological grade, more lymph node positivity, lower estrogen receptor (ER) positivity, higher rates of Her2/neu overexpression). Also, they tend to be diagnosed at more advanced stages of the disease. That, in turn, contributes to less favorable prognosis as compared to older women. Young women are generally treated similarly to older patients. Surgical management includes mastectomy or breast-conserving surgery, followed by radiation therapy (younger women have higher local recurrence rates than older women, especially after breast-conserving therapy). Although the basics of chemotherapy are the same for patients of all ages, younger women have some special considerations. It is important to consider options for fertility preservation before starting systemic treatment. Patients should have access to genetic testing as their results may affect the choice of therapy. Younger women and their families should receive adequate psychological support and counselling.

Breast density in multiethnic women presenting for screening mammography.

PubMed

Oppong, Bridget A; Dash, Chiranjeev; O'Neill, Suzanne; Li, Yinan; Makambi, Kepher; Pien, Edward; Makariou, Erini; Coleman, Tesha; Adams-Campbell, Lucile L

2018-05-01

Data on ethnic variations in breast density are limited and often not inclusive of underrepresented minorities. As breast density is associated with elevated breast cancer risk, investigating racial and ethnic difference may elucidate the observed differences in breast cancer risk among different populations. We reviewed breast density from initial screening of women from the Capital Breast Care Center and Georgetown University Hospital from 2010 to 2014. Patient demographics including race, age at screening, education, menopausal status, and body mass index were abstracted. We recorded the BI-RADS density categories: (1) "fatty," (2) "scattered fibroglandular densities," (3) "heterogeneously dense," and (4) "extremely dense." Multivariable unconditional logistic regression was used to identify predictors of breast density. Density categorization was recorded for 2146 women over the 5-year period, comprising Blacks (n = 940), Hispanics (n = 893), and Whites (n = 314). Analysis of subject characteristics by breast density showed that high category is observed in younger, Hispanic, nulliparous, premenopausal, and nonobese women (t-test or chi-square test, P-values <.0001). Obese women are 70% less likely to have high density. Being Hispanic, premenopausal, and nonobese were predictive of high density on logistic regression. In this analysis of density distribution in a diverse sample, Hispanic women have the highest breast density, followed by Blacks and Whites. Unique in our findings is women who identify as Hispanic have the highest breast density and lower rates of obesity. Further investigation of the impact of obesity on breast density, especially in the understudied Hispanic group is needed. © 2017 Wiley Periodicals, Inc.

Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models.

PubMed

Bahreini, Amir; Li, Zheqi; Wang, Peilu; Levine, Kevin M; Tasdemir, Nilgun; Cao, Lan; Weir, Hazel M; Puhalla, Shannon L; Davidson, Nancy E; Stern, Andrew M; Chu, David; Park, Ben Ho; Lee, Adrian V; Oesterreich, Steffi

2017-05-23

Mutations in the estrogen receptor alpha (ERα) 1 gene (ESR1) are frequently detected in ER+ metastatic breast cancer, and there is increasing evidence that these mutations confer endocrine resistance in breast cancer patients with advanced disease. However, their functional role is not well-understood, at least in part due to a lack of ESR1 mutant models. Here, we describe the generation and characterization of genome-edited T47D and MCF7 breast cancer cell lines with the two most common ESR1 mutations, Y537S and D538G. Genome editing was performed using CRISPR and adeno-associated virus (AAV) technologies to knock-in ESR1 mutations into T47D and MCF7 cell lines, respectively. Various techniques were utilized to assess the activity of mutant ER, including transactivation, growth and chromatin-immunoprecipitation (ChIP) assays. The level of endocrine resistance was tested in mutant cells using a number of selective estrogen receptor modulators (SERMs) and degraders (SERDs). RNA sequencing (RNA-seq) was employed to study gene targets of mutant ER. Cells with ESR1 mutations displayed ligand-independent ER activity, and were resistant to several SERMs and SERDs, with cell line and mutation-specific differences with respect to magnitude of effect. The SERD AZ9496 showed increased efficacy compared to other drugs tested. Wild-type and mutant cell co-cultures demonstrated a unique evolution of mutant cells under estrogen deprivation and tamoxifen treatment. Transcriptome analysis confirmed ligand-independent regulation of ERα target genes by mutant ERα, but also identified novel target genes, some of which are involved in metastasis-associated phenotypes. Despite significant overlap in the ligand-independent genes between Y537S and D538G, the number of mutant ERα-target genes shared between the two cell lines was limited, suggesting context-dependent activity of the mutant receptor. Some genes and phenotypes were unique to one mutation within a given cell line, suggesting a mutation-specific effect. Taken together, ESR1 mutations in genome-edited breast cancer cell lines confer ligand-independent growth and endocrine resistance. These biologically relevant models can be used for further mechanistic and translational studies, including context-specific and mutation site-specific analysis of the ESR1 mutations.

Testing the effects of narrative and play on physical activity among breast cancer survivors using mobile apps: study protocol for a randomized controlled trial.

PubMed

Lyons, Elizabeth J; Baranowski, Tom; Basen-Engquist, Karen M; Lewis, Zakkoyya H; Swartz, Maria C; Jennings, Kristofer; Volpi, Elena

2016-03-09

Physical activity reduces risk for numerous negative health outcomes, but postmenopausal breast cancer survivors do not reach recommended levels. Many interventions encourage self-monitoring of steps, which can increase physical activity in the short term. However, these interventions appear insufficient to increase motivation for sustained change. There is a need for innovative strategies to increase physical activity motivation in this population. Narratives are uniquely persuasive, and video games show promise for increasing motivation. This study will determine the effectiveness of an intervention that combines narrative and gaming to encourage sustained physical activity. SMARTGOAL (Self-Monitoring Activity: a Randomized Trial of Game-Oriented AppLications) is a randomized controlled intervention trial. The intervention period is six months, followed by a six month maintenance period. Participants (overweight, sedentary postmenopausal breast cancer survivors aged 45-75) will be randomized to a self-monitoring group or an enhanced narrative game group. The self-monitoring group will be encouraged to use a mobile application for self-monitoring and feedback and will receive 15 counseling phone calls emphasizing self-regulation. The narrative game group will be encouraged to use a mobile application that includes self-monitoring and feedback as well as a narrative-based active video game. The 15 calls for this group will emphasize concepts related to the game storyline. Counseling calls in both groups will occur weekly in months 1 - 3 and monthly in months 4 - 6. No counseling calls will occur after month 6, but both groups will be encouraged to continue using their apps. The primary outcome of the study is minutes of moderate to vigorous physical activity at six months. Other objectively measured outcomes include fitness and physical function. Self-reported outcomes include quality of life, depression, and motivation. This protocol will result in implementation and evaluation of two technology-based physical activity interventions among breast cancer survivors. Both interventions hold promise for broad dissemination. Understanding the potential benefit of adding narrative and game elements to interventions will provide critical information to interventionists, researchers, clinicians, and policymakers. This study is uniquely suited to investigate not just whether but how and why game elements may improve breast cancer survivors' health. clinicaltrials.gov NCT02341235 (January 9, 2015).

Met Nuclear Localization and Signaling in Breast Cancer

DTIC Science & Technology

2006-05-01

and in germinal regions of many tissues using 4 unique antibodies . Cell fractionation reveals a 60kDa band recognized by C-terminal Met antibodies ...cascades such as Gab1 , Grb2 and PI3K, leading to proliferation, scattering, increased motility, invasion and branching morphogenesis (reviewed in (2...Identification of Met antibodies for use on tissue microarray of normal and cancerous cells, Months 12-24 Task 2. Definition of the domain

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

PubMed

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S; Bowden, Michaela; Rao, Prakash; Long, Henry W; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-05-30

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance

PubMed Central

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S.; Bowden, Michaela; Rao, Prakash; Long, Henry W.; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-01-01

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2–ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists. PMID:28507152

Persistent breast pain among women with histories of breast conserving surgery for breast cancer compared to women without histories of breast surgery or cancer

PubMed Central

Edmond, Sara N.; Shelby, Rebecca A.; Keefe, Francis J.; Fisher, Hannah M.; Schmidt, John; Soo, Mary Scott; Skinner, Celette Sugg; Ahrendt, Gretchen M.; Manculich, Jessica; Sumkin, Jules H.; Zuley, Margarita L.; Bovbjerg, Dana H.

2016-01-01

Objectives This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer. Methods Breast cancer survivors (n=200) were recruited at their first post-surgical surveillance mammogram (6-15 months post-surgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected. Results Persistent breast pain (duration ≥ 6 months) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (p<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared to survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared to women without a breast cancer history. Discussion Results indicate that persistent breast pain negatively impacts women with a history of breast conserving cancer surgery compared to women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors. PMID:27922843

Broccoli Sprout Extract in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-04

Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Stomatitis associated with mammalian target of rapamycin inhibition: A review of pathogenesis, prevention, treatment, and clinical implications for oral practice in metastatic breast cancer.

PubMed

Chambers, Mark S; Rugo, Hope S; Litton, Jennifer K; Meiller, Timothy F

2018-04-01

Patients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care. The authors conducted a PubMed search from 2007 through 2017 using the terms "stomatitis," "mIAS," "everolimus," "mTOR," "metastatic breast cancer," and "oral care." They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines. mIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care. Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Ethnic disparities in breast cancer between Central Europe Caucasian women of Slavic origin and Middle East Turkish subjects.

PubMed

Zubor, P; Caliskan, M; Kajo, K; Soybir, G; Topuzlu, C; Danko, J

2014-01-01

The biological, cultural, behavioral and sociodemographic differences across populations modulate breast cancer profile among races or ethnics. Following this, we aimed to identify differences in breast cancer epidemiology, histopathology, and clinical presentation from representatives of central Europe (Slovakia) and Middle-East countries (Turkey) to point on ethnic disparities in cancer biology. The population based cross-sectional study analyzing 414 cases of primary breast carcinomas where 214 represented Caucasian and 200 Turkish subjects. The differences were found for age at the time of diagnosis (<0.0001), education, menopausal status (<0.001), tumor localization (<0.01), size (<0.0001), grade (<0.05) and axillary lymph node status (<0.001) between groups. Although carcinomas in Slovak subjects were of higher grade, negative axillary nodal status was more frequent finding compared to Turkish patients (50.0 vs. 41.0%). The Slovak group showed carcinomas to be more often ER positive (72.4 vs. 54.0%; <0.001), ER/PgR positive (54.6 vs. 49.0%; <0.001), of better Nottingham prognostic index (<0.001), and less frequent Her-2 positive (21.2 vs. 28.5%). Slovak population expressed significantly higher risk of non-sentinel lymph node metastases with increased tumor size, grade, vascular invasion and Her-2 positivity compared to Turkey population. The tumor size >2 cm and high tumor grade (G3) bears a risk of OR=7.62 and OR=3.10 in Slovak compared to OR=3.94 and OR=1.79 in Turkish cases, respectively.There are wide demographic and biological disparities in breast cancer between observed ethnics providing unique information for clinicians working at the level of screening or therapy in these populations.

Through the Lens of Culture: Quality of Life Among Latina Breast Cancer Survivors

PubMed Central

Graves, Kristi D.; Jensen, Roxanne E.; Cañar, Janet; Perret-Gentil, Monique; Leventhal, Kara-Grace; Gonzalez, Florencia; Caicedo, Larisa; Jandorf, Lina; Kelly, Scott; Mandelblatt, Jeanne

2012-01-01

BACKGROUND Latinas have lower quality of life than Caucasian cancer survivors but we know little about factors associated with quality of life in this growing population. METHODS Bilingual staff conducted interviews with a national cross-sectional sample of 264 Latina breast cancer survivors. Quality of life was measured using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Regression models evaluated associations between culture, social and medical context and overall quality of life and its subdomains. RESULTS Latina survivors were 1-5 years post-diagnosis and reported a lower mean quality of life score compared to other published reports of non-Latina survivors (M=105; SD=19.4 on the FACT-B). Culturally-based feelings of breast cancer-related stigma and shame were consistently related to lower overall quality of life and lower well-being in each quality of life domain. Social and medical contextual factors were independently related to quality of life; together cultural, social and medical context factors uniquely accounted for 62% of the explained model variance of overall quality of life (Adjusted R2=0.53, P<.001). Similar relationships were seen for quality of life subdomains in which cultural, social and medical contextual variables independently contributed to the overall variance of each final model: physical well-being (Adjusted R2=0.23, P <.001), social well-being (Adjusted R2=0.51, P<.001), emotional well-being (Adjusted R2=0.28, P<.001), functional well-being (Adjusted R2=0.41, P<.001) and additional breast concerns (Adjusted R2=0.40, P<.001). CONCLUSIONS Efforts to improve Latinas’ survivorship experiences should consider cultural, social and medical contextual factors to close existing quality of life gaps between Latinas and other survivors. PMID:23085764

Next-generation sequencing of the BRCA1 and BRCA2 genes for the genetic diagnostics of hereditary breast and/or ovarian cancer.

PubMed

Trujillano, Daniel; Weiss, Maximilian E R; Schneider, Juliane; Köster, Julia; Papachristos, Efstathios B; Saviouk, Viatcheslav; Zakharkina, Tetyana; Nahavandi, Nahid; Kovacevic, Lejla; Rolfs, Arndt

2015-03-01

Genetic testing for hereditary breast and/or ovarian cancer mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the BRCA1 and BRCA2 genes. We explored a more efficient genetic screening strategy based on next-generation sequencing of the BRCA1 and BRCA2 genes in 210 hereditary breast and/or ovarian cancer patients. We first validated this approach in a cohort of 115 samples with previously known BRCA1 and BRCA2 mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq BRCA1 and BRCA2 panel. The DNA Libraries were pooled, barcoded, and sequenced using an Ion Torrent Personal Genome Machine sequencer. The combination of different robust bioinformatics tools allowed detection of all previously known pathogenic mutations and polymorphisms in the 115 samples, without detecting spurious pathogenic calls. We then used the same assay in a discovery cohort of 95 uncharacterized hereditary breast and/or ovarian cancer patients for BRCA1 and BRCA2. In addition, we describe the allelic frequencies across 210 hereditary breast and/or ovarian cancer patients of 74 unique definitely and likely pathogenic and uncertain BRCA1 and BRCA2 variants, some of which have not been previously annotated in the public databases. Targeted next-generation sequencing is ready to substitute classic molecular methods to perform genetic testing on the BRCA1 and BRCA2 genes and provides a greater opportunity for more comprehensive testing of at-risk patients. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Facets of Spirituality as Predictors of Adjustment to Cancer: Relative Contributions of Having Faith and Finding Meaning

PubMed Central

Yanez, Betina; Edmondson, Donald; Stanton, Annette L.; Park, Crystal L.; Kwan, Lorna; Ganz, Patricia A.; Blank, Thomas O.

2009-01-01

Spirituality is a multidimensional construct, and little is known about how its distinct dimensions jointly affect well-being. In longitudinal studies (Study 1, N = 418 breast cancer patients; Study 2, N = 165 cancer survivors), we examined two components of spiritual well-being (i.e., meaning/peace and faith) and their interaction, as well as change scores on those variables, as predictors of psychological adjustment. In Study 1, higher baseline meaning/peace, as well as an increase in meaning/peace over six months, predicted a decline in depressive symptoms and an increase in vitality across 12 months in breast cancer patients. Baseline faith predicted an increase in perceived cancer-related growth. Study 2 revealed that an increase in meaning/peace was related to improved mental health and lower cancer-related distress. An increase in faith was related to increased cancer-related growth. Both studies revealed significant interactions between meaning/peace and faith in predicting adjustment. Findings suggest that the ability to find meaning and peace in life is the more influential contributor to favorable adjustment during cancer survivorship, although faith appears to be uniquely related to perceived cancer-related growth. PMID:19634965

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

PubMed

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

ClinicalTrials.gov

2018-03-30

BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

ClinicalTrials.gov

2017-05-22

Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

ClinicalTrials.gov

2018-02-08

Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

Ginseng in Decreasing Cancer-Related Fatigue After Treatment in Cancer Survivors

ClinicalTrials.gov

2018-03-15

Cancer Survivor; Stage I Breast Cancer AJCC v7; Stage I Colon Cancer AJCC v6 and v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage II Colon Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIA Colon Cancer AJCC v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIB Colon Cancer AJCC v7; Stage IIC Colon Cancer AJCC v7; Stage III Breast Cancer AJCC v7; Stage III Colon Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

PubMed

Hartmaier, R J; Trabucco, S E; Priedigkeit, N; Chung, J H; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-04-01

Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

[Breast lesions of a metastatic melanoma on a radiotherapy territory: Treatment by vemurafenib and carcinologic surgery].

PubMed

Fernandez, J; Montaudié, H; Courdi, A; Georgiou, C; Camuzard, O; Chignon-Sicard, B

2016-02-01

This article describes the unique case of a female patient who presented distant melanoma metastasis on the breast while having irradiation therapy for breast cancer. This happened eight months after the initial treatment for a melanoma of the back (under the right scapula). Furthermore, this case report demonstrates the efficiency of Vemurafenib® as a treatment for late stage melanomas. The patient was a 47-year-old female that had a superficial spreading melanoma under the right scapula (Breslow 1.02mm) that was treated with 2cm skin excision and sentinel lymph node sampling that was negative. The melanoma was positive for the BRAF600E mutation. One month after this incident, the patient developed breast cancer that was treated with conservative surgery and radiotherapy. Three months after the end of the irradiation treatment, she developed multiple melanoma metastasis on the skin of the breast. Our multidisciplinary team decided to initiate a treatment with vemurafenib. The patient showed an excellent response, so the surgical team completed the treatment with a radical mastectomy and immediate reconstruction with a pedicled latissimus dorsi flap. The histologic report of the mastectomy specimen showed no sign of melanocytic proliferation, that demonstrates the efficacy of vemurafenib. The patient showed no relapse after two years of follow-up. The speed of development and location of cutaneous metastases in this case brought us to think about the effects of radiation therapy on the skin. Radiation therapy causes acute complications (radiodermatitis) by cellular and molecular mechanisms. Moreover, depressed immunity is found after irradiation. Association of these mecanisms could explain the appearance of these metastases in irradiation field. The efficiency of vemurafenib found in our case is consistent with what is described in literature, especially with the improvement in median overall survival. This case demonstrates a unique case of distant melanoma metastasis on the irradiation field of a breast cancer. It also demonstrates the efficacy of vemurafenib as well as the efficacy of a radical complementary surgical treatment in these patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer

ClinicalTrials.gov

2018-04-05

Androgen Receptor Positive; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel With or Without Carboplatin in Treating Patients With Triple-Negative Breast Cancer

ClinicalTrials.gov

2016-10-04

Breast Adenocarcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Examination of Duct Physiology in the Human Mammary Gland

PubMed Central

Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

2016-01-01

Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

In vitro characterization of cancer cell morphology, chemokinesis, and matrix invasion using a novel microfabricated system

NASA Astrophysics Data System (ADS)

Blaha, Laura

A diagnosis of metastatic cancer reduces a patient's 5-year survival rate by nearly 80% compared to a primary tumor diagnosed at an early stage. While gene expression arrays have revealed unique gene signatures for metastatic cancer cells, we are lacking an understanding of the tangible physical changes that distinguish metastatic tumor cells from each other and from their related primary tumors. At the fundamental level, this translates into first characterizing the phenotype of metastatic cancer cells in vitro both in 2D - looking at morphology and migration - and in 3D - focusing on matrix invasion. While 2D in vitro studies have provided insight into the effects of specific environmental conditions on specific cancer cell lines, the unique details included in each experimental design make it challenging to compare cell phenotype across different in vitro platforms as well as between laboratories and disciplines that share the goal of understanding cancer. While 3D phenotype studies have employed more standardized and ubiquitous assays, most available tools lack the imaging capability and geometry to effectively characterize all factors driving 3D matrix invasion. In this work, we present protocols and platforms aimed at addressing the problems identified in the tools currently available for studying metastatic cancer in vitro. First, we present a 2D study of morphology and migration using widely accepted protocols. The study is applied to characterizing phenotypes of three breast cancer cell lines with different metastatic organ tropisms. The results show that general populations of cells from each of the 3 lines are unique in shape and motility despite being derived from the same tumor line and that the observed phenotype differences may be related to differences in focal adhesion assembly. More broadly, these studies suggest that standardizing phenotype studies using commonly available techniques may provide a platform by which to compare phenotypic studies across cancer cell types and between research groups to investigate tropism-specific cancer phenotypes. We conclude our investigation of phenotype with a study of 3D matrix invasion using a novel microfluidic platform. The results show that invasion of metastatic breast cancer cells into a 3D type I collagen gel is significantly enhanced in the presence of live endothelial cells. In applying the model to study cell-cell and cell-matrix interactions driving invasion, our platform revealed that, while the fibronectin-rich matrix deposited by endothelial cells was not sufficient to drive invasion alone, metastatic breast cancer cells were able to exploit a structural or secreted component of energetically inactivated endothelial cell to gain entry into the underlying matrix. These findings have important implications for designing drugs targeted at preventing cancer metastasis. The findings in this dissertation reveal significant phenotypic differences in metastatic breast cancer cells with different preferences in metastatic target organ. In addition, the microfluidic platform reveals novel cell-cell interactions driving a key step in the seeding and colonization of a metastatic tumor. Collectively, these results reveal important characteristics of metastatic cancer cells and their interactions with other cell types during metastasis. These studies also provide platforms on which to target or prevent malignant phenotypes and cellular interactions in the future.

S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)

ClinicalTrials.gov

2018-03-20

Febrile Neutropenia; Stage 0 Breast Cancer; Stage 0 Colorectal Cancer; Stage 0 Non-Small Cell Lung Cancer; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Breast Cancer; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Breast Density Legislation: Discussion of Patient Utilization and Subsequent Direct Financial Ramifications for Insurance Providers.

PubMed

Sobotka, John; Hinrichs, Clay

2015-10-01

Now that New Jersey has become the 14th state in the United States to enact legislation regarding dense breast screening, its patients are eligible to receive screening breast sonography coverage from their insurance carriers. This law is intended to improve breast cancer detection in patients with dense breasts and create awareness of unique issues that come with dense breast tissue, while reinforcing already present efforts to reduce the incidence of and morbidity related to the diagnosis of breast cancer. The aim of this study was to examine data from months preceding the effective date of this legislation in a community hospital setting and compare these data with data from months immediately after, and 6 months after, its enactment to present patient participation data and estimate the legislation's direct financial ramifications. Detractors of this type of legislation worry about overburdening the health care system with an influx of patients. Although there is a lack of present studies confirming this suspicion in other states with dense breast legislation, this study confirms a large increase in patient utilization after enactment, showing a minimum relative increase of 176.90% and a maximum relative increase of 335.56% in patient utilization of screening breast sonography. The investigators further include an estimation of an increased direct cost for insurers of $4,910,899.18 to $9,848,897.96 for a given month. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer

ClinicalTrials.gov

2018-04-03

Estrogen Receptor Status; HER2/Neu Negative; Invasive Breast Carcinoma; Postmenopausal; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

KeraStat Skin Therapy in Treating Radiation Dermatitis in Patients With Newly Diagnosed Stage 0-IIIA Breast Cancer

ClinicalTrials.gov

2017-05-25

Ductal Breast Carcinoma in Situ; Skin Reactions Secondary to Radiation Therapy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Characterization and discrimination of human breast cancer and normal breast tissues using resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Wu, Binlin; Smith, Jason; Zhang, Lin; Gao, Xin; Alfano, Robert R.

2018-02-01

Worldwide breast cancer incidence has increased by more than twenty percent in the past decade. It is also known that in that time, mortality due to the affliction has increased by fourteen percent. Using optical-based diagnostic techniques, such as Raman spectroscopy, has been explored in order to increase diagnostic accuracy in a more objective way along with significantly decreasing diagnostic wait-times. In this study, Raman spectroscopy with 532-nm excitation was used in order to incite resonance effects to enhance Stokes Raman scattering from unique biomolecular vibrational modes. Seventy-two Raman spectra (41 cancerous, 31 normal) were collected from nine breast tissue samples by performing a ten-spectra average using a 500-ms acquisition time at each acquisition location. The raw spectral data was subsequently prepared for analysis with background correction and normalization. The spectral data in the Raman Shift range of 750- 2000 cm-1 was used for analysis since the detector has highest sensitivity around in this range. The matrix decomposition technique nonnegative matrix factorization (NMF) was then performed on this processed data. The resulting leave-oneout cross-validation using two selective feature components resulted in sensitivity, specificity and accuracy of 92.6%, 100% and 96.0% respectively. The performance of NMF was also compared to that using principal component analysis (PCA), and NMF was shown be to be superior to PCA in this study. This study shows that coupling the resonance Raman spectroscopy technique with subsequent NMF decomposition method shows potential for high characterization accuracy in breast cancer detection.

Interactions of Family History of Breast Cancer with Radiotherapy in Relation to the Risk of Breast Cancer Recurrence.

PubMed

Li, Danmeng; Mai, Volker; Gerke, Travis; Pinney, Susan Mengel; Yaghjyan, Lusine

2017-12-01

We examined associations between a family history of breast cancer and the risk of breast cancer recurrence in women who received or did not receive radiotherapy. Our study included 2,440 women enrolled in the Breast Cancer Registry of Greater Cincinnati. Information on breast cancer risk factors, including detailed family history of breast cancer, characteristics of the primary tumor, treatment received, and recurrence status was collected at baseline and via updates. Associations between a family history of breast cancer and the risk of breast cancer recurrence were examined separately in women treated with and without radiotherapy using survival analysis. Over an average follow-up time of 8.78 years, we found no associations between a family history of breast cancer and the risk of breast cancer recurrence among women with a history of radiotherapy (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.75-1.23). Among women who did not receive radiotherapy, the total number of relatives with breast cancer was positively associated with the risk of breast cancer recurrence (HR, 1.21; 95% CI, 1.00-1.47). We found no interactions of radiotherapy with family history (p-interaction >0.05). Radiotherapy for a primary breast cancer in women with a family history of breast cancer does not increase risk of breast cancer recurrence. If these findings are replicated in future studies, the results may translate into an important health message for breast cancer survivors with a family history of breast cancer.

The need for supplemental breast cancer screening modalities: a perspective of population-based breast cancer screening programs in Japan.

PubMed

Uematsu, Takayoshi

2017-01-01

This article discusses possible supplemental breast cancer screening modalities for younger women with dense breasts from a perspective of population-based breast cancer screening program in Japan. Supplemental breast cancer screening modalities have been proposed to increase the sensitivity and detection rates of early stage breast cancer in women with dense breasts; however, there are no global guidelines that recommend the use of supplemental breast cancer screening modalities in such women. Also, no criterion standard exists for breast density assessment. Based on the current situation of breast imaging in Japan, the possible supplemental breast cancer screening modalities are ultrasonography, digital breast tomosynthesis, and breast magnetic resonance imaging. An appropriate population-based breast cancer screening program based on the balance between cost and benefit should be a high priority. Further research based on evidence-based medicine is encouraged. It is very important that the ethnicity, workforce, workflow, and resources for breast cancer screening in each country should be considered when considering supplemental breast cancer screening modalities for women with dense breasts.

RO4929097 and Whole-Brain Radiation Therapy or Stereotactic Radiosurgery in Treating Patients With Brain Metastases From Breast Cancer

ClinicalTrials.gov

2015-01-22

Estrogen Receptor-negative Breast Cancer; Extensive Stage Small Cell Lung Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Tumors Metastatic to Brain; Unspecified Adult Solid Tumor, Protocol Specific

Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer

ClinicalTrials.gov

2018-04-06

Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Breast Cancer Brain Metastases: Clonal Evolution in Clinical Context.

PubMed

Saunus, Jodi M; McCart Reed, Amy E; Lim, Zhun Leong; Lakhani, Sunil R

2017-01-13

Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management.

Breast cancer screening

MedlinePlus

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... performed to screen women to detect early breast cancer when it is more likely to be cured. ...

Awareness and current knowledge of breast cancer.

PubMed

Akram, Muhammad; Iqbal, Mehwish; Daniyal, Muhammad; Khan, Asmat Ullah

2017-10-02

Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

Pembrolizumab and Capecitabine in Treating Patients With Locally Advanced or Metastatic Triple Negative or Hormone-Refractory Breast Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-03-15

Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-06-08

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

PubMed

Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

2018-04-09

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

Integrative Tumor Board: a Case Report and Discussion from Dana-Farber Cancer Institute

PubMed Central

Lu, Weidong; Ott, Mary Jane; Kennedy, Stacy; Mathay, Maria B.; Doherty-Gilman, Anne M.; Dean-Clower, Elizabeth; Hayes, Carolyn M.; Rosenthal, David S.

2010-01-01

A 34-year-old female carrying a BRCA1 gene and a significant family history was diagnosed with T1c, N1 breast cancer. The tumor was estrogen receptor, progesterone receptor and HER-2/Neu negative. The patient received dose-dense chemotherapy with Adriamycin and Cytoxan followed by Taxol, and left breast irradiation. Later, a bilateral S-GAP flap reconstruction with right prophylactic mastectomy and left mastectomy were performed. During her treatment, the patient had an integrative medicine consultation and was seen by a team of healthcare providers specializing in integrative therapies including integrative nutrition, therapeutic massage, acupuncture, and yoga. Each modality contributed unique benefit in her care that led to a satisfactory outcome of the patient. A detailed discussion regarding her care from each modality is presented. The case elucidates the need of integrative approaches for cancer patients in a conventional medical setting. PMID:19815593

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

ClinicalTrials.gov

2018-04-09

Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

A Study of Neoadjuvant Paclitaxel in Combination With Bavituximab in Early- Stage Triple- Negative Breast Cancer

ClinicalTrials.gov

2017-03-08

Breast Cancer; Triple Negative Breast Neoplasms; Triple-Negative Breast Neoplasm; Triple-Negative Breast Cancer; Triple Negative Breast Cancer; ER-Negative PR-Negative HER2-Negative Breast Neoplasms; ER-Negative PR-Negative HER2-Negative Breast Cancer

2D/ 3D Quantitative Ultrasound of the Breast

NASA Astrophysics Data System (ADS)

Nasief, Haidy Gerges

Breast cancer is the second leading cause of cancer death of women in the United States, so breast cancer screening for early detection is common. The purpose of this dissertation is to optimize quantitative ultrasound (QUS) methods to improve the specificity and objectivity of breast ultrasound. To pursue this goal, the dissertation is divided into two parts: 1) to optimize 2D QUS, and 2) to introduce and validate 3D QUS. Previous studies had validated these methods in phantoms. Applying our QUS analysis on subcutaneous breast fat demonstrated that QUS parameter estimates for subcutaneous fat were consistent among different human subjects. This validated our in vivo data acquisition methods and supported the use of breast fat as a clinical reference tissue for ultrasound BI-RADSRTM assessments. Although current QUS methods perform well for straightforward cases when assumptions of stationarity and diffuse scattering are well-founded, these conditions often are not present due to the complicated nature of in vivo breast tissue. Key improvements in QUS algorithms to address these challenges were: 1) applying a "modified least squares method (MLSM)" to account for the heterogeneous tissue path between the transducer and the region of interest, ROI; 2) detecting anisotropy in acoustic parameters; and 3) detecting and removing the echo sources that depart from diffuse and stationary scattering conditions. The results showed that a Bayesian classifier combining three QUS parameters in a biased pool of high-quality breast ultrasound data successfully differentiated all fibroadenomas from all carcinomas. Given promising initial results in 2D, extension to 3D acquisitions in QUS provided a unique capability to test QUS for the entire breast volume. QUS parameter estimates using 3D data were consistent with those found in 2D for phantoms and in vivo data. Extensions of QUS technology from 2D to 3D can improve the specificity of breast ultrasound, and thus, could lead to improved screening with this modality.

Full Intelligent Cancer Classification of Thermal Breast Images to Assist Physician in Clinical Diagnostic Applications

PubMed Central

Lashkari, AmirEhsan; Pak, Fatemeh; Firouzmand, Mohammad

2016-01-01

Breast cancer is the most common type of cancer among women. The important key to treat the breast cancer is early detection of it because according to many pathological studies more than 75% – 80% of all abnormalities are still benign at primary stages; so in recent years, many studies and extensive research done to early detection of breast cancer with higher precision and accuracy. Infra-red breast thermography is an imaging technique based on recording temperature distribution patterns of breast tissue. Compared with breast mammography technique, thermography is more suitable technique because it is noninvasive, non-contact, passive and free ionizing radiation. In this paper, a full automatic high accuracy technique for classification of suspicious areas in thermogram images with the aim of assisting physicians in early detection of breast cancer has been presented. Proposed algorithm consists of four main steps: pre-processing & segmentation, feature extraction, feature selection and classification. At the first step, using full automatic operation, region of interest (ROI) determined and the quality of image improved. Using thresholding and edge detection techniques, both right and left breasts separated from each other. Then relative suspected areas become segmented and image matrix normalized due to the uniqueness of each person's body temperature. At feature extraction stage, 23 features, including statistical, morphological, frequency domain, histogram and Gray Level Co-occurrence Matrix (GLCM) based features are extracted from segmented right and left breast obtained from step 1. To achieve the best features, feature selection methods such as minimum Redundancy and Maximum Relevance (mRMR), Sequential Forward Selection (SFS), Sequential Backward Selection (SBS), Sequential Floating Forward Selection (SFFS), Sequential Floating Backward Selection (SFBS) and Genetic Algorithm (GA) have been used at step 3. Finally to classify and TH labeling procedures, different classifiers such as AdaBoost, Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naïve Bayes (NB) and probability Neural Network (PNN) are assessed to find the best suitable one. These steps are applied on different thermogram images degrees. The results obtained on native database showed the best and significant performance of the proposed algorithm in comprise to the similar studies. According to experimental results, GA combined with AdaBoost with the mean accuracy of 85.33% and 87.42% on the left and right breast images with 0 degree, GA combined with AdaBoost with mean accuracy of 85.17% on the left breast images with 45 degree and mRMR combined with AdaBoost with mean accuracy of 85.15% on the right breast images with 45 degree, and also GA combined with AdaBoost with a mean accuracy of 84.67% and 86.21%, on the left and right breast images with 90 degree, are the best combinations of feature selection and classifier for evaluation of breast images. PMID:27014608

Second cancers in patients with male breast cancer: a literature review.

PubMed

Grenader, Tal; Goldberg, Anthony; Shavit, Linda

2008-06-01

The risk of second malignancies among female breast cancer patients has been studied for decades. In contrast, very little is known about second primary tumors in men. Risk factors for breast cancer in men, including genetic, hormonal and environmental factors, provide parallels to the etiology of breast cancer in women. This review considers the literature related to the risk of developing a second cancer in patients with male breast cancer. A systematic review of the literature between 1966 and 2007 was conducted and acceptable articles used for analysis. All retrieved articles were screened to identify any papers that had been missed. Studies were included if they discussed the risk of subsequent malignancy in patients with male breast cancer. Patients with history of male breast cancer have an increased risk of a second ipsilateral, or contralateral breast cancer (standardized incidence ratio 30-110). The risk of subsequent contralateral breast cancer was highest in men under 50 years of age at the time of the diagnosis of the initial cancer. The data on non-breast second primary cancers is diverse. One study has suggested an increased incidence of cancers of the small intestine, prostate, rectum and pancreas, and of non-melanoma skin cancer and myeloid leukaemia. Other investigators did not find an increase in the overall risk of subsequent cancer development in men diagnosed initially with primary breast cancer. Although sarcoma, lung and esophageal cancers are well recognized complications of radiation therapy for female breast cancer, there is no evidence for the association of these cancers following radiation therapy in male breast cancer. Although the incidence of second primary cancer in patients with primary male breast cancer requires further study, male breast cancer survivors should probably undergo periodic screening for the early detection of second breast cancers and other adverse health effects.

Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

ClinicalTrials.gov

2018-05-01

HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

A Unique Opportunity to Test Whether Cell Fusion is a Mechanism of Breast Cancer Metastasis

DTIC Science & Technology

2012-07-01

tetraploid with numerous structural rearrangements. The observations that a majority of cancer cell lines in the NCI-60 drug screening panel99 and...optimized electroporation conditions for T47D and human mesenchymal stem cell populations. As a result we have been able to conduct our first co...specific receptor-ligand interactions necessary for cell fusion, to produce a target for drug therapy. Post-fusion events might also be investigated

Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2013-09-27

Adenocarcinoma of the Gastroesophageal Junction; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy

ClinicalTrials.gov

2018-04-18

Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

ClinicalTrials.gov

2017-06-07

Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

HER2-positive male breast cancer with thyroid cancer: an institutional report and review of literature.

PubMed

Bardhan, Pooja; Bui, Marilyn M; Minton, Susan; Loftus, Loretta; Carter, W Bradford; Laronga, Christine; Ismail-Khan, Roohi

2012-01-01

We report a rare finding of two male breast cancer patients with HER2-positive breast cancer who also developed thyroid cancer. We reviewed 45 male breast cancer patients treated in our institution from 2003 to 2008. Only five male breast cancer patients were HER2-positive. In reviewing the published data, we found no cases of thyroid cancer and concurrent breast cancer in men. However, breast cancer and thyroid cancer have shown close association in women. This finding therefore provokes speculation as to whether we should investigate whether women with HER2-positive breast cancer are at a higher risk for thyroid cancer. Although this observation seems to be clinically prevalent, publications are sparse in clinical research areas linking thyroid cancer to breast cancer.

Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

ClinicalTrials.gov

2018-01-22

BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma In Situ; Lobular Breast Carcinoma In Situ; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

PubMed

Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

2017-06-01

Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density. Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1 st -degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density. Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density. Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history. Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR . ©2017 American Association for Cancer Research.

Breast Cancer Overview

MedlinePlus

... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

Vinorelbine induced perforation of a metastatic gastric lesion.

PubMed

Mullally, W J; O'Súilleabháin, C B; Brady, C; O'Reilly, S

2017-08-01

Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted in gastric perforation. Five years after gastric perforation she resumed palliative chemotherapy after progression on sequential hormonal therapies.

Molecular evaluation of PIK3CA gene mutation in breast cancer: determination of frequency, distribution pattern and its association with clinicopathological findings in Indian patients.

PubMed

Ahmad, Firoz; Badwe, Anuya; Verma, Geeta; Bhatia, Simi; Das, Bibhu Ranjan

2016-07-01

Somatic mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful marker for prognosis and therapeutic target. Activating mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in 18-40 % of breast carcinomas. In this study, we evaluated PIK3CA mutation in 185 Indian breast cancer patients by direct DNA sequencing. PIK3CA mutations were observed in 23.2 % (43/185) of breast tumor samples. PIK3CA mutations were more frequent exon 30 (76.8 %) than in exon 9 (23.2 %). Mutations were mostly clustered within two hotspot region between nucleotides 1624 and 1636 or between 3129 and 3140. Sequencing analysis revealed four different missense mutations at codon 542 and 545 (E542K, E545K, E545A and E545G) in the helical domain and two different amino acid substitutions at codon 1047 (H1047R and H1047L) in the kinase domain. None of the cases harbored concomitant mutations at multiple codons. PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non-DCIS tumors; however, none of the differences were significant. In addition, PIK3CA mutations were common in ER+, PR+ and HER2+ cases (30 %), and a comparatively low frequency were noted in triple-negative tumors (13.6 %). In conclusion, to our knowledge, this is the largest study to evaluate the PIK3CA mutation in Indian breast cancer patients. The frequency and distribution pattern of PIK3CA mutations is similar to global reports. Furthermore, identification of molecular markers has unique strengths and can provide insights into the pathogenic process of breast carcinomas.

Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

ClinicalTrials.gov

2017-09-25

Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms.

PubMed

Wheler, Jennifer J; Parker, Barbara A; Lee, Jack J; Atkins, Johnique T; Janku, Filip; Tsimberidou, Apostolia M; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Schwab, Richard; Moulder, Stacy; Valero, Vicente; Schwaederle, Maria; Yelensky, Roman; Miller, Vincent A; Stephens, M Philip J; Meric-Bernstam, Funda; Kurzrock, Razelle

2014-05-15

Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.

Therapies for Cognitive Deficits Associated With Chemotherapy for Breast Cancer: A Systematic Review of Objective Outcomes.

PubMed

Morean, Diane F; O'Dwyer, Linda; Cherney, Leora R

2015-10-01

To systematically review evidence of treatments for cognitive impairments experienced by at least 20% of all women who undergo chemotherapy for breast cancer. Searches of 5 databases (PubMed, Embase, Cochrane CENTRAL, PsycINFO, CINAHL), with no date or language restrictions, identified 1701 unique results. Search terms included breast cancer, chemotherapy, chemobrain, chemofog, and terms on cognition and language deficits. Included only peer-reviewed journal articles that described therapies for cognitive dysfunction in women undergoing (or who had undergone) chemotherapy for breast cancer and provided objective measurements of cognition or language. Data were extracted according to Cochrane recommendations, including characteristics of participants, interventions, outcomes, and studies. Quality assessment of all 12 eligible studies was performed using the Physiotherapy Evidence Database scale and treatment fidelity criteria. Screening, data extraction, and quality assessment reliability were performed. Six articles described interventions for cognition that took place during cancer treatment; 6, afterward. Five interventions were medical (including a strength-training program), 2 were restorative, and 5 were cognitive. Medicinal treatments were ineffective; restorative and exercise treatments had mixed results; cognitive therapy had success in varying cognitive domains. The domains most tested and most successfully treated were verbal memory, attention, and processing speed. Cognitive therapy protocols delivered after chemotherapy and aimed at improving verbal memory, attention, and processing speed hold the most promise. Future research is needed to clarify whether computerized cognitive training can be effective in treating this population, and to identify objective assessment tools that are sensitive to this disorder. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pazopanib inhibits the activation of PDGFRβ-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells.

PubMed

Gril, Brunilde; Palmieri, Diane; Qian, Yongzhen; Anwar, Talha; Liewehr, David J; Steinberg, Seth M; Andreu, Zoraida; Masana, Daniel; Fernández, Paloma; Steeg, Patricia S; Vidal-Vanaclocha, Fernando

2013-06-01

Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor β (at tyrosine 751; p751-PDGFRβ) was identified around perivascular brain micrometastases. p751-PDGFRβ(+) astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRβ(+) astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

PubMed Central

Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jing; Sun, Qian; Guan, Xiaoxiang

2017-01-01

ABSTRACT Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy. PMID:28272969

Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

ClinicalTrials.gov

2018-06-26

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Breast Cancer -- Male

MedlinePlus

... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

ClinicalTrials.gov

2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

Estrogen response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the coexistence of multiple estrogen-deprivation resistant mechanisms.

PubMed

Fujiki, Natsu; Konno, Hiromi; Kaneko, Yosuke; Gohno, Tatsuyuki; Hanamura, Toru; Imami, Koshi; Ishihama, Yasushi; Nakanishi, Kyoko; Niwa, Toshifumi; Seino, Yuko; Yamaguchi, Yuri; Hayashi, Shin-ichi

2014-01-01

The acquisition of estrogen-deprivation resistance and estrogen receptor (ER) signal-independence in ER-positive breast cancer is one of the crucial steps in advancing the aggressiveness of breast cancer; however, this has not yet been elucidated in detail. To address this issue, we established several estrogen-deprivation-resistant (EDR) breast cancer cell lines from our unique MCF-7 cells, which had been stably transfected with an ERE-GFP reporter plasmid. Three cell lines with high ER activity and another 3 cell lines with no ER activity were established from cell cloning by monitoring GFP expression in living cells. The former three ERE-GFP-positive EDR cell lines showed the overexpression of ER and high expression of several ER-target genes. Further analysis of intracellular signaling factors revealed a marked change in the phosphorylation status of ERα on Ser167 and Akt on Thr308 by similar mechanisms reported previously; however, we could not find any changes in MAP-kinase factors. Comprehensive phospho-proteomic analysis also indicated the possible contribution of the Akt pathway to the phosphorylation of ERα. On the other hand, constitutive activation of c-Jun N-terminal kinase (JNK) was observed in ERE-GFP-negative EDR cells, and the growth of these cells was inhibited by a JNK inhibitor. An IGF1R-specific inhibitor diminished the phosphorylation of JNK, which suggested that a novel signaling pathway, IGF1R-JNK, may be important for the proliferation of ER-independent MCF-7 cells. These results indicate that ER-positive breast cancer cells can acquire resistance by more than two mechanisms at a time, which suggests that multiple mechanisms may occur simultaneously. This finding also implies that breast cancers with different resistance mechanisms can concomitantly occur and mingle in an individual patient, and may be a cause of the recurrence of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of diet and exercise on weight-related outcomes for breast cancer survivors and their adult daughters: an analysis of the DAMES trial.

PubMed

Tometich, Danielle B; Mosher, Catherine E; Winger, Joseph G; Badr, Hoda J; Snyder, Denise C; Sloane, Richard J; Demark-Wahnefried, Wendy

2017-08-01

Few trials have aimed to promote diet and exercise behaviors in both cancer survivors and their family members and examine their associations with weight-related outcomes. We conducted a secondary analysis to examine associations between change in diet and exercise behaviors and weight-related outcomes for overweight breast cancer survivors and their overweight adult daughters in the Daughters And MothErS Against Breast Cancer (DAMES) randomized trial. The DAMES trial assessed the impact of two iteratively tailored, mailed print diet and exercise interventions against standard brochures over a 12-month period. This analysis examined change in diet and exercise behaviors and weight-related variables from baseline to post-intervention for the 50 breast cancer survivors and their adult daughters randomized to the intervention arms. To reduce the potential for type II error in this pilot, p values <0.10 were considered statistically significant. For mothers, change in diet quality was uniquely related to change in BMI (β = -0.12, p = 0.082), weight (β = -0.12, p = 0.060), and waist circumference (β = -0.38, p = 0.001), whereas change in caloric intake was related to waist circumference (β = 0.21, p = 0.002). For daughters, change in caloric intake was related to change in waist circumference (β = 0.12, p = 0.055). However, change in diet quality was not associated with weight-related outcomes in daughters. Additionally, change in exercise was not associated with weight-related outcomes in mothers or daughters. Findings support mail-based and other tailored interventions for weight loss in this population, with an emphasis on diet quality for breast cancer survivors and caloric intake for their adult daughters.

Malignancy during pregnancy in Japan: an exceptional opportunity for early diagnosis.

PubMed

Sekine, Masayuki; Kobayashi, Yoshiyuki; Tabata, Tsutomu; Sudo, Tamotsu; Nishimura, Ryuichiro; Matsuo, Koji; Grubbs, Brendan H; Enomoto, Takayuki; Ikeda, Tomoaki

2018-02-08

Malignancy during pregnancy has become a significant cause of maternal death in developed countries, likely due to both an older pregnant population, and increases of cervical cancer in younger women. Our aim is to investigate the clinical aspects of malignancy during pregnancy in Japan and to use this information to identify opportunities for earlier detection and treatment. We provided a questionnaire to 1508 secondary or tertiary care hospitals in Japan. We reviewed the clinical characteristics of cases with malignancy during pregnancy for the period of January to December, 2008. From the 760 institutions which responded, we obtained clinical information for 227 unique cases. The questionnaire provided clinical information, including disease site, pregnancy outcome and how the disease was detected. The most common type of malignancy was cervical cancer (n = 162, 71.4%) followed by ovarian (n = 16, 7.0%) and breast cancer (n = 15, 6.6%). Leukemia (n = 7, 3.1%), colon cancer (n = 5, 2.2%), gastric cancer (n = 5, 2.2%), malignant lymphoma (n = 4, 1.8%), thyroid cancer (n = 3, 1.3%), brain cancer (n = 3, 1.3%), endometrial cancer (n = 2, 0.9%), and head and neck cancer (n = 2, 0.9%) accounted for the remaining cases. Overall, gynecological malignancies accounted for 79.3% (95% confidence interval 74.0-84.6) of pregnancy associated malignancies diagnosed in the present study. The majority of cervical cancers, 149 (92.0%) of 162, were diagnosed by a Pap (Papanicolaou) smear during early gestation. Ten (62.5%) of the ovarian cancer cases were diagnosed by ultrasonography during a prenatal checkup or at the time of initial pregnancy diagnosis. Out of 14 breast cancers, only one (7.1%) was diagnosed by screening breast exam. From this study, we reaffirm the clear and significant benefits of prenatal checkups starting at an early gestational age for the detection of gynecological cancers during pregnancy. Conversely, breast cancer detection during pregnancy was poor, suggesting new strategies for early identification of this disease are required.

Breast Cancer Surgery

MedlinePlus

FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

Photothermal-triggered control of sub-cellular drug accumulation using doxorubicin-loaded single-walled carbon nanotubes for the effective killing of human breast cancer cells

NASA Astrophysics Data System (ADS)

Oh, Yunok; Jin, Jun-O.; Oh, Junghwan

2017-03-01

Single-walled carbon nanotubes (SWNTs) are often the subject of investigation as effective photothermal therapy (PTT) agents owing to their unique strong optical absorption. Doxorubicin (DOX)-loaded SWNTs (SWNTs-DOX) can be used as an efficient therapeutic agent for combined near infrared (NIR) cancer photothermal and chemotherapy. However, SWNTs-DOX-mediated induction of cancer cell death has not been fully investigated, particularly the reaction of DOX inside cancer cells by PTT. In this study, we examined how the SWNTs-DOX promoted effective MDA-MB-231 cell death compared to DOX and PTT alone. We successfully synthesized the SWNTs-DOX. The SWNTs-DOX exhibited a slow DOX release, which was accelerated by NIR irradiation. Furthermore, DOX released from the SWNTs-DOX accumulated inside the cells at high concentration and effectively localized into the MDA-MB-231 cell nucleus. A combination of SWNTs-DOX and PTT promoted an effective MDA-MB-231 cell death by mitochondrial disruption and ROS generation. Thus, SWNTs-DOX can be utilized as an excellent anticancer agent for early breast cancer treatment.

Wnt-Responsive Cancer Stem Cells Are Located Close to Distorted Blood Vessels and Not in Hypoxic Regions in a p53-Null Mouse Model of Human Breast Cancer

PubMed Central

Landua, John D.; Bu, Wen; Wei, Wei; Li, Fuhai; Wong, Stephen T.C.; Dickinson, Mary E.; Rosen, Jeffrey M.; Lewis, Michael T.

2014-01-01

Cancer stem cells (CSCs, or tumor-initiating cells) may be responsible for tumor formation in many types of cancer, including breast cancer. Using high-resolution imaging techniques, we analyzed the relationship between a Wnt-responsive, CSC-enriched population and the tumor vasculature using p53-null mouse mammary tumors transduced with a lentiviral Wnt signaling reporter. Consistent with their localization in the normal mammary gland, Wnt-responsive cells in tumors were enriched in the basal/myoepithelial population and generally located in close proximity to blood vessels. The Wnt-responsive CSCs did not colocalize with the hypoxia-inducible factor 1α-positive cells in these p53-null basal-like tumors. Average vessel diameter and vessel tortuosity were increased in p53-null mouse tumors, as well as in a human tumor xenograft as compared with the normal mammary gland. The combined strategy of monitoring the fluorescently labeled CSCs and vasculature using high-resolution imaging techniques provides a unique opportunity to study the CSC and its surrounding vasculature. PMID:24797826

Gold Nanoantenna-Mediated Photothermal Drug Delivery from Thermosensitive Liposomes in Breast Cancer.

PubMed

Ou, Yu-Chuan; Webb, Joseph A; Faley, Shannon; Shae, Daniel; Talbert, Eric M; Lin, Sharon; Cutright, Camden C; Wilson, John T; Bellan, Leon M; Bardhan, Rizia

2016-08-31

In this work, we demonstrate controlled drug delivery from low-temperature-sensitive liposomes (LTSLs) mediated by photothermal heating from multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. The unique geometry of MGNs enables the generation of mild hyperthermia (∼42 °C) by converting near-infrared light to heat and effectively delivering doxorubicin (DOX) from the LTSLs in breast cancer cells. We confirmed the cellular uptake of MGNs by using both fluorescence confocal Z-stack imaging and transmission electron microscopy (TEM) imaging. We performed a cellular viability assay and live/dead cell fluorescence imaging of the combined therapeutic effects of MGNs with DOX-loaded LTSLs (DOX-LTSLs) and compared them with free DOX and DOX-loaded non-temperature-sensitive liposomes (DOX-NTSLs). Imaging of fluorescent live/dead cell indicators and MTT assay outcomes both demonstrated significant decreases in cellular viability when cells were treated with the combination therapy. Because of the high phase-transition temperature of NTSLs, no drug delivery was observed from the DOX-NTSLs. Notably, even at a low DOX concentration of 0.5 μg/mL, the combination treatment resulted in a higher (33%) cell death relative to free DOX (17% cell death). The results of our work demonstrate that the synergistic therapeutic effect of photothermal hyperthermia of MGNs with drug delivery from the LTSLs can successfully eradicate aggressive breast cancer cells with higher efficacy than free DOX by providing a controlled light-activated approach and minimizing off-target toxicity.

Gold Nanoantenna-Mediated Photothermal Drug Delivery from Thermosensitive Liposomes in Breast Cancer

PubMed Central

2016-01-01

In this work, we demonstrate controlled drug delivery from low-temperature-sensitive liposomes (LTSLs) mediated by photothermal heating from multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. The unique geometry of MGNs enables the generation of mild hyperthermia (∼42 °C) by converting near-infrared light to heat and effectively delivering doxorubicin (DOX) from the LTSLs in breast cancer cells. We confirmed the cellular uptake of MGNs by using both fluorescence confocal Z-stack imaging and transmission electron microscopy (TEM) imaging. We performed a cellular viability assay and live/dead cell fluorescence imaging of the combined therapeutic effects of MGNs with DOX-loaded LTSLs (DOX-LTSLs) and compared them with free DOX and DOX-loaded non-temperature-sensitive liposomes (DOX-NTSLs). Imaging of fluorescent live/dead cell indicators and MTT assay outcomes both demonstrated significant decreases in cellular viability when cells were treated with the combination therapy. Because of the high phase-transition temperature of NTSLs, no drug delivery was observed from the DOX-NTSLs. Notably, even at a low DOX concentration of 0.5 μg/mL, the combination treatment resulted in a higher (33%) cell death relative to free DOX (17% cell death). The results of our work demonstrate that the synergistic therapeutic effect of photothermal hyperthermia of MGNs with drug delivery from the LTSLs can successfully eradicate aggressive breast cancer cells with higher efficacy than free DOX by providing a controlled light-activated approach and minimizing off-target toxicity. PMID:27656689

Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

PubMed Central

Balasundaram, Ghayathri; Ho, Chris Jun Hui; Li, Kai; Driessen, Wouter; Dinish, US; Wong, Chi Lok; Ntziachristos, Vasilis; Liu, Bin; Olivo, Malini

2015-01-01

Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications. PMID:25609951

Metabolic Syndrome and Breast Cancer Risk.

PubMed

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-28

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tissue phosphoproteomics with PolyMAC identifies potential therapeutic targets in a transgenic mouse model of HER2 positive breast cancer

PubMed Central

Searleman, Adam C.; Iliuk, Anton B.; Collier, Timothy S.; Chodosh, Lewis A.; Tao, W. Andy; Bose, Ron

2014-01-01

Altered protein phosphorylation is a feature of many human cancers that can be targeted therapeutically. Phosphopeptide enrichment is a critical step for maximizing the depth of phosphoproteome coverage by MS, but remains challenging for tissue specimens because of their high complexity. We describe the first analysis of a tissue phosphoproteome using polymer-based metal ion affinity capture (PolyMAC), a nanopolymer that has excellent yield and specificity for phosphopeptide enrichment, on a transgenic mouse model of HER2-driven breast cancer. By combining phosphotyrosine immunoprecipitation with PolyMAC, 411 unique peptides with 139 phosphotyrosine, 45 phosphoserine, and 29 phosphothreonine sites were identified from five LC-MS/MS runs. Combining reverse phase liquid chromatography fractionation at pH 8.0 with PolyMAC identified 1571 unique peptides with 1279 phosphoserine, 213 phosphothreonine, and 21 phosphotyrosine sites from eight LC-MS/MS runs. Linear motif analysis indicated that many of the phosphosites correspond to well-known phosphorylation motifs. Analysis of the tyrosine phosphoproteome with the Drug Gene Interaction database uncovered a network of potential therapeutic targets centered on Src family kinases with inhibitors that are either FDA-approved or in clinical development. These results demonstrate that PolyMAC is well suited for phosphoproteomic analysis of tissue specimens. PMID:24723360

CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.

PubMed

Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E

2012-12-10

We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.

A preclinical mouse model of invasive lobular breast cancer metastasis.

PubMed

Doornebal, Chris W; Klarenbeek, Sjoerd; Braumuller, Tanya M; Klijn, Christiaan N; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W; Jonkers, Jos; de Visser, Karin E

2013-01-01

Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous breast cancer metastasis, which recapitulates key events in its formation and clinical course. Specifically, using the conditional K14cre;Cdh1(F/F);Trp53(F/F) model of de novo mammary tumor formation, we orthotopically transplanted invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once primary tumors were established in recipient mice, we mimicked the clinical course of treatment by conducting a mastectomy. After surgery, recipient mice succumbed to widespread overt metastatic disease in lymph nodes, lungs, and gastrointestinal tract. Genomic profiling of paired mammary tumors and distant metastases showed that our model provides a unique tool to further explore the biology of metastatic disease. Neoadjuvant and adjuvant intervention studies using standard-of-care chemotherapeutics showed the value of this model in determining therapeutic agents that can target early- and late-stage metastatic disease. In obtaining a more accurate preclinical model of metastatic lobular breast cancer, our work offers advances supporting the development of more effective treatment strategies for metastatic disease.

Breast cancer: updates and advances in 2016.

PubMed

Giordano, Sara B; Gradishar, William

2017-02-01

Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment. Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment. This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

PubMed Central

2009-01-01

Background Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. Methods The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. Results Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. Conclusion We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy. PMID:19799784

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells.

PubMed

Xiao, Yan; Gao, Xiugong; Taratula, Oleh; Treado, Stephen; Urbas, Aaron; Holbrook, R David; Cavicchi, Richard E; Avedisian, C Thomas; Mitra, Somenath; Savla, Ronak; Wagner, Paul D; Srivastava, Sudhir; He, Huixin

2009-10-02

Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy.

Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer

PubMed Central

Leygue, Etienne

2007-01-01

The steroid receptor RNA activator (SRA) is a unique modulator of steroid receptor transcriptional activity, as it is able to mediate its coregulatory effects as a RNA molecule. Recent findings, however, have painted a more complex picture of the SRA gene (SRA1) products. Indeed, even though SRA was initially thought to be noncoding, several RNA isoforms have now been found to encode an endogenous protein (SRAP), which is well conserved among Chordata. Although the function of SRAP remains largely unknown, it has been proposed that, much like its corresponding RNA, the protein itself might regulate estrogen and androgen receptor signaling pathways. As such, data suggest that both SRA and SRAP might participate in the mechanisms underlying breast, as well as prostate tumorigenesis. This review summarizes the published literature dealing with these two faces of the SRA gene products and underscores the relevance of this bifaceted system to breast cancer development. PMID:17710122

Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection.

PubMed

Lee, Su Hyun; Chang, Jung Min; Shin, Sung Ui; Chu, A Jung; Yi, Ann; Cho, Nariya; Moon, Woo Kyung

2017-12-01

To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review. DBT features and the cancer detectability score according to molecular subtype were compared using Fisher's exact test and analysis of variance. Of 288 invasive cancers, 194 were hormone receptor (HR)-positive, 48 were human epidermal growth factor receptor 2 (HER2) positive and 46 were triple negative breast cancers. The most common DBT findings were irregular spiculated masses for HR-positive cancer, fine pleomorphic or linear branching calcifications for HER2 positive cancer and irregular masses with circumscribed margins for triple negative breast cancers (p < 0.001). Cancer detectability on DBT was not significantly different according to molecular subtype (p = 0.213) but rather affected by tumour size, breast density and presence of mass or calcifications. Breast cancers showed different imaging features according to molecular subtype; however, it did not affect the cancer detectability on DBT. Advances in knowledge: DBT showed characteristic imaging features of breast cancers according to molecular subtype. However, cancer detectability on DBT was not affected by molecular subtype of breast cancers.

Nipple aspirate fluid-A liquid biopsy for diagnosing breast health.

PubMed

Shaheed, Sadr-Ul; Tait, Catherine; Kyriacou, Kyriacos; Mullarkey, Joanne; Burrill, Wayne; Patterson, Laurence H; Linforth, Richard; Salhab, Mohamed; Sutton, Chris W

2017-09-01

Nipple secretions are protein-rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra- and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies. Matched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS-PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin-digested peptides analyzed using 2D-LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance. A total of 1990 unique proteins were identified many of which are established cancer-associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed. This was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient-specific protein levels but changes relating to cancer stage require investigation of a larger cohort. © 2017 The Authors. PROTEOMICS-Clinical Applications published by WILEY-VCH Verlag GmbH & Co. KGaA.

Dose-dependent effect of mammographic breast density on the risk of contralateral breast cancer.

PubMed

Chowdhury, Marzana; Euhus, David; O'Donnell, Maureen; Onega, Tracy; Choudhary, Pankaj K; Biswas, Swati

2018-07-01

Increased mammographic breast density is a significant risk factor for breast cancer. It is not clear if it is also a risk factor for the development of contralateral breast cancer. The data were obtained from Breast Cancer Surveillance Consortium and included women diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 18 and 88 and years 1995 and 2009. Each case of contralateral breast cancer was matched with three controls based on year of first breast cancer diagnosis, race, and length of follow-up. A total of 847 cases and 2541 controls were included. The risk factors included in the study were mammographic breast density, age of first breast cancer diagnosis, family history of breast cancer, anti-estrogen treatment, hormone replacement therapy, menopausal status, and estrogen receptor status, all from the time of first breast cancer diagnosis. Both univariate analysis and multivariate conditional logistic regression analysis were performed. In the final multivariate model, breast density, family history of breast cancer, and anti-estrogen treatment remained significant with p values less than 0.01. Increasing breast density had a dose-dependent effect on the risk of contralateral breast cancer. Relative to 'almost entirely fat' category of breast density, the adjusted odds ratios (and p values) in the multivariate analysis for 'scattered density,' 'heterogeneously dense,' and 'extremely dense' categories were 1.65 (0.036), 2.10 (0.002), and 2.32 (0.001), respectively. Breast density is an independent and significant risk factor for development of contralateral breast cancer. This risk factor should contribute to clinical decision making.

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

ClinicalTrials.gov

2018-06-11

Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7

Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis

PubMed Central

Smith, S. G.; Sestak, I.; Forster, A.; Partridge, A.; Side, L.; Wolf, M. S.; Horne, R.; Wardle, J.; Cuzick, J.

2016-01-01

Background Preventive therapy is a risk reduction option for women who have an increased risk of breast cancer. The effectiveness of preventive therapy to reduce breast cancer incidence depends on adequate levels of uptake and adherence to therapy. We aimed to systematically review articles reporting uptake and adherence to therapeutic agents to prevent breast cancer among women at increased risk, and identify the psychological, clinical and demographic factors affecting these outcomes. Design Searches were carried out in PubMed, CINAHL, EMBASE and PsychInfo, yielding 3851 unique articles. Title, abstract and full text screening left 53 articles, and a further 4 studies were identified from reference lists, giving a total of 57. This review was prospectively registered with PROSPERO (CRD42014014957). Results Twenty-four articles reporting 26 studies of uptake in 21 423 women were included in a meta-analysis. The pooled uptake estimate was 16.3% [95% confidence interval (CI) 13.6–19.0], with high heterogeneity (I2 = 98.9%, P < 0.001). Uptake was unaffected by study location or agent, but was significantly higher in trials [25.2% (95% CI 18.3–32.2)] than in non-trial settings [8.7% (95% CI 6.8–10.9)] (P < 0.001). Factors associated with higher uptake included having an abnormal biopsy, a physician recommendation, higher objective risk, fewer side-effect or trial concerns, and older age. Adherence (day-to-day use or persistence) over the first year was adequate. However, only one study reported a persistence of ≥80% by 5 years. Factors associated with lower adherence included allocation to tamoxifen (versus placebo or raloxifene), depression, smoking and older age. Risk of breast cancer was discussed in all qualitative studies. Conclusion Uptake of therapeutic agents for the prevention of breast cancer is low, and long-term persistence is often insufficient for women to experience the full preventive effect. Uptake is higher in trials, suggesting further work should focus on implementing preventive therapy within routine care. PMID:26646754

Epigenetic suppression of neprilysin regulates breast cancer invasion

PubMed Central

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-01-01

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer. PMID:26950599

Epigenetic suppression of neprilysin regulates breast cancer invasion.

PubMed

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-03-07

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-16

Advanced Malignant Solid Neoplasm; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Castration-Resistant Prostate Carcinoma; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Prostate Carcinoma; PIK3CB Gene Mutation; Progesterone Receptor Negative; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; PTEN Gene Mutation; PTEN Loss; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer

ClinicalTrials.gov

2018-03-22

Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Metastatic Malignant Solid Neoplasm; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Unresectable Solid Neoplasm

Veliparib and Atezolizumab Either Alone or in Combination in Treating Patients With Stage III-IV Triple Negative Breast Cancer

ClinicalTrials.gov

2018-03-20

BRCA1 Gene Mutation; BRCA2 Gene Mutation; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma

Breast Cancer Knowledge among College Students: Influencing Factors and Resultant Behaviors

ERIC Educational Resources Information Center

Justice, Mary F.; King, Keith A.; Vidourek, Rebecca A.; Merianos, Ashley L.

2018-01-01

Background: Many misconceptions about breast cancer exist. College students have the opportunity to perform breast cancer risk-reducing behaviors. Purpose: The purpose of this study was to assess breast cancer knowledge among university students and examine the influence of breast cancer knowledge on health behaviors for breast cancer prevention.…

Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast.

PubMed

Lee, Kunsei; Kim, Hyeongsu; Lee, Jung Hyun; Jeong, Hyoseon; Shin, Soon Ae; Han, Taehwa; Seo, Young Lan; Yoo, Youngbum; Nam, Sang Eun; Park, Jong Heon; Park, Yoo Mi

2016-11-18

The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rate of interval cancer of the breast were calculated. The crude detection rate of breast cancer screening per 100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive predictive value of breast cancer screening per 100,000 positives increased from 741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014 and the specificities were 83.1% in 2009 and 85.7% in 2014. To increase the detection rate of breast cancer by breast cancer screening using mammography, the participation rate should be higher and an environment where accurate mammography and reading can be performed and reinforcement of quality control are required. To reduce the incidence rate of interval cancer of the breast, it will be necessary to educate women after their 20s to perform self-examination of the breast once a month regardless of participation in screening for breast cancer.

Social Media and the Adolescent and Young Adult (AYA) patient with Cancer

PubMed Central

Perales, Miguel-Angel; Drake, Emily K; Pemmaraju, Naveen; Wood, William A

2016-01-01

Over 70,000 adolescent and young adults aged 15 to 39 years (AYA) are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data, but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90% of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs. PMID:26893061

Social Media and the Adolescent and Young Adult (AYA) Patient with Cancer.

PubMed

Perales, Miguel-Angel; Drake, Emily K; Pemmaraju, Naveen; Wood, William A

2016-12-01

Over 70,000 adolescent and young adults (AYA) aged 15 to 39 years are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer, and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90 % of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs.

Fatigue Interventions in Cancer (Exercise Intervention)

ClinicalTrials.gov

2018-01-29

Sedentary Lifestyle; Stage III Breast Cancer AJCC v7; Stage III Prostate Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7

Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: A meta-analysis.

PubMed

Chen, Yan; Shi, Xiu-E; Tian, Jin-Hui; Yang, Xu-Juan; Wang, Yong-Feng; Yang, Ke-Hu

2018-05-01

Neoadjuvant chemotherapy (NAC) increases breast conservation rates in patients with resectable breast cancer at the associated cost of higher locoregional recurrence rates; however, the magnitude of the survival benefits of NAC for these patients remains undefined. Therefore, we aimed to clarify the survival benefit of NAC versus postoperative chemotherapy by conducting an updated meta-analysis of randomized clinical trials (RCTs). The authors searched the Cochrane Library, PubMed, Embase, Web of Science, Chinese biomedical literature database, and Chinese Scientific Journals full-text database from their inception to December 2016. The authors identified relevant RCTs that compared NAC with postoperative chemotherapy in the treatment of operable breast cancer. The main endpoints were overall survival (OS) and recurrence-free survival (RFS). A total of 21 citations representing 16 unique studies were eligible. There were 787 deaths among 2794 patients assigned to NAC groups and 816 deaths among 2799 patients assigned to adjuvant chemotherapy groups. A meta-analysis of data indicated that there was no significant benefit in terms of OS ([hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.94-1.13, P = .51) and RFS (HR = 1.01, 95% CI: 0.93-1.10, P = .80) between the NAC and postoperative chemotherapy groups. The pooled HR estimate for OS was not influenced by NAC cycles, the total number of chemotherapy cycles, administration of tamoxifen, administration of adjuvant chemotherapy, or type of NAC regimen. Subgroup analysis showed that the pooled HR estimate for RFS was influenced by anthracycline-containing regimens. Patients with a pathological complete response had superior survival outcomes compared with patients who had residual disease. The survival benefits for patients with operable breast cancer who received either NAC or adjuvant chemotherapy based on anthracycline regimens were comparable.

Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

NASA Astrophysics Data System (ADS)

Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

2018-03-01

Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (p<0.05). We applied our optimized imaging protocol to clinical samples and demonstrated significantly greater uptake of HS-27 by tumor than non-tumor tissue (p<0.05). The ubiquitous nature of HS-27 binding to all subtypes of breast cancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

Breast Cancer in Men

MedlinePlus

FACTS FOR LIFE Breast Cancer in Men Do men get breast cancer? Since men have breast tissue, they can get breast cancer, but it’s rare. About 1 percent of ... breast cancer cases in the U.S. occur in men. It may sound like a small number, but ...

Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program.

PubMed

Castells, Xavier; Domingo, Laia; Corominas, Josep María; Torá-Rocamora, Isabel; Quintana, María Jesús; Baré, Marisa; Vidal, Carmen; Natal, Carmen; Sánchez, Mar; Saladié, Francina; Ferrer, Joana; Vernet, Mar; Servitja, Sonia; Rodríguez-Arana, Ana; Roman, Marta; Espinàs, Josep Alfons; Sala, María

2015-01-01

Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

PubMed

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS hybrid clones exhibited a mesenchymal phenotype and, with the exception of one hybrid clone, responded to EGF with an increased migratory activity. Fusion of human breast epithelial cells and human breast cancer cells can give rise to hybrid clone cells that possess certain CS/IC properties, suggesting that cell fusion might be a mechanism underlying how tumor cells exhibiting a CS/IC phenotype could originate.

Common breast cancer susceptibility loci are associated with triple negative breast cancer

PubMed Central

Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

2012-01-01

Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer.

PubMed

Kuhlman, Kate Ryan; Boyle, Chloe C; Irwin, Michael R; Ganz, Patricia A; Crespi, Catherine M; Asher, Arash; Petersen, Laura; Bower, Julienne E

2017-10-01

Childhood maltreatment is associated with elevated risk for depression across the human lifespan. Identifying the pathways through which childhood maltreatment relates to depressive symptoms may elucidate intervention targets that have the potential to reduce the lifelong negative health sequelae of maltreatment exposure. In this cross-sectional study, 271 women with early-stage breast cancer were assessed after their diagnosis but before the start of adjuvant treatment (chemotherapy, radiation, endocrine therapy). Participants completed measures of childhood maltreatment exposure, psychological resources (optimism, mastery, self-esteem, mindfulness), and depressive symptoms. Using multiple mediation analyses, we examined which psychological resources uniquely mediated the relationship between childhood maltreatment and depressive symptoms. Exposure to maltreatment during childhood was robustly associated with lower psychological resources and elevated depressive symptoms. Further, lower optimism and mindfulness mediated the association between childhood maltreatment and elevated depressive symptoms. These results support existing theory that childhood maltreatment is associated with lower psychological resources, which partially explains elevated depressive symptoms in a sample of women facing breast cancer diagnosis and treatment. These findings warrant replication in populations facing other major life events and highlight the need for additional studies examining childhood maltreatment as a moderator of treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis

PubMed Central

Deakin, Nicholas O.; Turner, Christopher E.

2011-01-01

Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herein we show that the focal adhesion adaptor protein, paxillin, and the closely related Hic-5 have distinct and unique roles in the regulation of breast cancer cell lung metastasis by modulating cell morphology and cell invasion through three-dimensional extracellular matrices (3D ECMs). Cells depleted of paxillin by RNA interference displayed a highly elongated mesenchymal morphology, whereas Hic-5 knockdown induced an amoeboid phenotype with both cell populations exhibiting reduced plasticity, migration persistence, and velocity through 3D ECM environments. In evaluating associated signaling pathways, we determined that Rac1 activity was increased in cells devoid of paxillin whereas Hic-5 silencing resulted in elevated RhoA activity and associated Rho kinase–induced nonmuscle myosin II activity. Hic-5 was essential for adhesion formation in 3D ECMs, and analysis of adhesion dynamics and lifetime identified paxillin as a key regulator of 3D adhesion assembly, stabilization, and disassembly. PMID:21148292

Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced Breast Cancer

ClinicalTrials.gov

2018-06-22

Estrogen Receptor Positive; HER2/Neu Positive; Progesterone Receptor Positive; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Patient navigation in breast cancer: a systematic review.

PubMed

Robinson-White, Stephanie; Conroy, Brenna; Slavish, Kathleen H; Rosenzweig, Margaret

2010-01-01

The role of the patient navigator in cancer care and specifically in breast cancer care has grown to incorporate many titles and functions. To better evaluate the outcomes of patient navigation in breast cancer care, a comprehensive review of empiric literature detailing the efficacy of breast cancer navigation on breast cancer outcomes (screening, diagnosis, treatment, and participation in clinical research) was performed. Published articles were reviewed if published in the scientific literature between January 1990 and April 2009. Searches were conducted using PubMed and Ovid databases. Search terms included MeSH (Medical Subject Headings) terms, "patient navigator," "navigation," "breast cancer," and "adherence." Data-based literature indicates that the role of patient navigation is diverse with multiple roles and targeted populations. Navigation across many aspects of the breast cancer disease trajectory improves adherence to breast cancer care. The empiric review found that navigation interventions have been more commonly applied in breast cancer screening and early diagnosis than for adherence to treatment. There is evidence supporting the role of patient navigation in breast cancer to improve many aspects of breast cancer care. Data describing the role of patient navigation in breast cancer will assist in better defining future direction for the breast navigation role. Ongoing research will better inform issues related to role definition, integration into clinical breast cancer care, impact on quality of life, cost-effectiveness, and sustainability.

Addressing Breast Cancer's Unequal Burden | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn JavaScript on. Feature: Breast Cancer Addressing Breast Cancer's Unequal Burden Past Issues / Winter 2017 Table of ... What are trends in African-American women and breast cancer? Breast cancer is the most commonly diagnosed cancer ...

Frequency of breast cancer, lung cancer, and tobacco use articles in women's magazines from 1987 to 2003.

PubMed

Tobler, Kyle J; Wilson, Philip K; Napolitano, Peter G

2009-01-01

The objective of this study was to compare the frequency of articles in women's magazines that address breast cancer, lung cancer, and tobacco use from 1987-2003 and to ascertain whether the annual number of articles reflected corresponding cancer mortality rates from breast cancer and lung cancer and the number of female smokers throughout this time period. We reviewed 13 women's magazines published in the United States from 1987-2003 using the search terms breast cancer, lung cancer, smoking, and tobacco. We reviewed the abstracts or entire articles to determine relevance. A total of 1044 articles addressed breast cancer, lung cancer, or tobacco use: 681 articles related to breast cancer, 47 related to lung cancer, and 316 related to tobacco use. The greater number of breast cancer articles compared to lung cancer articles was statistically significant (P value < .0001). The greater number of breast cancer articles compared to lung cancer articles combined with tobacco use articles was also statistically significant (P = .0012). The annual number breast cancer articles compared to the breast cancer mortality rate demonstrated a negative relationship. The annual number of lung cancer articles compared to the lung cancer mortality rate demonstrated no relationship. The annual number of tobacco use articles compared to the annual number of female smokers demonstrated no relationship. Breast cancer was more frequently represented than lung cancer or tobacco use in women's magazines from 1987-2003 despite the increase in lung cancer mortality, a decrease in breast cancer mortality, and an insignificant change in the number of female smokers.

6 Common Cancers - Breast Cancer

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

PIPAC Nab-pac for Stomach, Pancreas, Breast and Ovarian Cancer

ClinicalTrials.gov

2018-05-31

Peritoneal Carcinomatosis; Ovarian Cancer Stage IIIB; Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV; Breast Cancer Stage IIIB; Breast Cancer Stage IIIc; Breast Cancer Stage IV; Stomach Cancer Stage III; Stomach Cancer Stage IV With Metastases; Pancreas Cancer, Stage III; Pancreas Cancer, Stage IV

Occupational exposure and risk of breast cancer

PubMed Central

FENGA, CONCETTINA

2016-01-01

Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID:26998264

Evidence that breast tissue stiffness is associated with risk of breast cancer.

PubMed

Boyd, Norman F; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J; Minkin, Salomon

2014-01-01

Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

ClinicalTrials.gov

2018-06-19

Breast Adenocarcinoma; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7

The effect of knowledge on uptake of breast cancer prevention modalities among women in Kyadondo County, Uganda.

PubMed

Atuhairwe, Christine; Amongin, Dinah; Agaba, Elly; Mugarura, Steven; Taremwa, Ivan M

2018-02-23

Breast cancer, the third most frequent cancer of women is preventable through knowledge on breast self-examination. Of the 44% of women diagnosed with breast cancer at the Uganda Cancer Institute, only 22% go for check-up in less than three months. This study explored the effect of breast cancer knowledge on the uptake of breast cancer prevention modalities among women in Kyadondo County, Uganda. A household survey of women in Kyadondo County was conducted during June, 2014 to August, 2015. This involved studying in-depth using a questionnaire the level of breast cancer knowledge of the respondents. Data was analyzed using logistic regression model. Chi-square test was used to establish relationships between knowledge base factors and the uptake of breast cancer prevention modalities. This study has established an empirical relationship between uptake of breast cancer prevention modalities and source of information especially radio (OR 1.94 95% CI: 1.16-3.24), television (OR 1.82 95%CI: 1.14-2.93), awareness of breast cancer (OR 4.03 95%CI: 1.01-15.98), knowledge on how to reduce risk of breast cancer (OR 1.98 95% CI: 1.20-3.27), what reduces breast cancer acquisition (OR 2.75 95% CI: 1.42-5.35), how to check for signs of breast cancer especially through breast self-examination (OR 3.09 95% CI: 1.62-5.88), and other methods of breast cancer diagnosis in a health care set up. The women's level of breast cancer awareness as a primary prevention strategy was found wanting, and requires a boost through community health education.

Olaparib In Metastatic Breast Cancer

ClinicalTrials.gov

2018-03-27

Metastatic Breast Cancer; Invasive Breast Cancer; Somatic Mutation Breast Cancer (BRCA1); Somatic Mutation Breast Cancer (BRCA2); CHEK2 Gene Mutation; ATM Gene Mutation; PALB2 Gene Mutation; RAD51 Gene Mutation; BRIP1 Gene Mutation; NBN Gene Mutation

Mitoguazone induces apoptosis via a p53-independent mechanism.

PubMed

Davidson, K; Petit, T; Izbicka, E; Koester, S; Von Hoff, D D

1998-08-01

Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.

Topical Network of Breast Cancer Information in a Korean American Online Community: A Semantic Network Analysis

ERIC Educational Resources Information Center

Park, Min Sook; Park, Hyejin

2016-01-01

Introduction: Health information-seeking and sharing online has become immensely intertwined with day-to-day information-seeking of US immigrants with health concerns. Despite the consistent recognition of unique health needs among different US immigrant communities, little is known about the distinctive patterns and extent of health information…

Unique Gene Expression Profiles in the Mammary Gland of Prepubertal and Adult Female Rats Treated With Estradiol or Soy Protein Isolate (SPI)

USDA-ARS?s Scientific Manuscript database

Concerns have arisen regarding infertility and increased breast cancer risk in women consuming soy foods, primarily because of the perceived estrogenicity of soy isoflavones such as genistein and daidzein. Two studies were conducted in mammary gland to determine if consumption of soy products induce...

Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.

PubMed

Mavaddat, Nasim; Peock, Susan; Frost, Debra; Ellis, Steve; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Izatt, Louise; Eeles, Rosalind A; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Porteous, Mary E; Morrison, Patrick J; Side, Lucy E; Kennedy, M John; Houghton, Catherine; Donaldson, Alan; Rogers, Mark T; Dorkins, Huw; Miedzybrodzka, Zosia; Gregory, Helen; Eason, Jacqueline; Barwell, Julian; McCann, Emma; Murray, Alex; Antoniou, Antonis C; Easton, Douglas F

2013-06-05

Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers. The aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles. Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks were obtained using Kaplan-Meier estimates. Associations between cancer risk and covariables of interest were evaluated using Cox regression. All statistical tests were two-sided. The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2 carriers in the highest tertile of risk, defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk, were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile (hazard ratio = 4.1, 95% CI = 1.2 to 14.5; P = .02). Prospective risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast, ovarian, and contralateral breast cancer. Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.

Screen-detected versus interval cancers: Effect of imaging modality and breast density in the Flemish Breast Cancer Screening Programme.

PubMed

Timmermans, Lore; Bleyen, Luc; Bacher, Klaus; Van Herck, Koen; Lemmens, Kim; Van Ongeval, Chantal; Van Steen, Andre; Martens, Patrick; De Brabander, Isabel; Goossens, Mathieu; Thierens, Hubert

2017-09-01

To investigate if direct radiography (DR) performs better than screen-film mammography (SF) and computed radiography (CR) in dense breasts in a decentralized organised Breast Cancer Screening Programme. To this end, screen-detected versus interval cancers were studied in different BI-RADS density classes for these imaging modalities. The study cohort consisted of 351,532 women who participated in the Flemish Breast Cancer Screening Programme in 2009 and 2010. Information on screen-detected and interval cancers, breast density scores of radiologist second readers, and imaging modality was obtained by linkage of the databases of the Centre of Cancer Detection and the Belgian Cancer Registry. Overall, 67% of occurring breast cancers are screen detected and 33% are interval cancers, with DR performing better than SF and CR. The interval cancer rate increases gradually with breast density, regardless of modality. In the high-density class, the interval cancer rate exceeds the cancer detection rate for SF and CR, but not for DR. DR is superior to SF and CR with respect to cancer detection rates for high-density breasts. To reduce the high interval cancer rate in dense breasts, use of an additional imaging technique in screening can be taken into consideration. • Interval cancer rate increases gradually with breast density, regardless of modality. • Cancer detection rate in high-density breasts is superior in DR. • IC rate exceeds CDR for SF and CR in high-density breasts. • DR performs better in high-density breasts for third readings and false-positives.

Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer

PubMed Central

Mao, Weimin; Chen, Bo; Yang, Shifeng; Ding, Xiaowen; Zou, Dehong; Mo, Wenju; He, Xiangming; Zhang, Xiping

2017-01-01

Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future. PMID:28938549

Maastricht Delphi Consensus on Event Definitions for Classification of Recurrence in Breast Cancer Research

PubMed Central

van Roozendaal, Lori M.; Strobbe, Luc J. A.; Aebi, Stefan; Cameron, David A.; Dixon, J. Michael; Giuliano, Armando E.; Haffty, Bruce G.; Hickey, Brigid E.; Hudis, Clifford A.; Klimberg, V. Suzanne; Koczwara, Bogda; Kühn, Thorsten; Lippman, Marc E.; Lucci, Anthony; Piccart, Martine; Smith, Benjamin D.; Tjan-Heijnen, Vivianne C. G.; van de Velde, Cornelis J. H.; Van Zee, Kimberly J.; Vermorken, Jan B.; Viale, Giuseppe; Voogd, Adri C.; Wapnir, Irene L.; White, Julia R.; Smidt, Marjolein L.

2014-01-01

Background In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, “local recurrence” may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. Methods The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. Results Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. Conclusion This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis. PMID:25381395

Do breast implants adversely affect prognosis among those subsequently diagnosed with breast cancer? Findings from an extended follow-up of a Canadian cohort.

PubMed

Lavigne, Eric; Holowaty, Eric J; Pan, Sai Yi; Xie, Lin; Villeneuve, Paul J; Morrison, Howard; Brisson, Jacques

2012-10-01

Cosmetic breast implants may impair the ability to detect breast cancers. The aims of this study were to examine whether implants and implant characteristics are associated with more advanced breast tumors at diagnosis and poorer survival. Study population includes all invasive breast cancer cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A total of 409 women with cosmetic breast implants and 444 women with other cosmetic surgery were diagnosed with breast cancer. These women were compared for stage at diagnosis using multinomial logistic regression models. Cox proportional hazards regression models were used for breast cancer-specific mortality analyses. Comparisons were also conducted according to implant characteristics. Compared with women with other cosmetic surgery, those with cosmetic breast implants had at later stage breast cancer diagnosis (OR of having stage III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81-5.10; P < 0.001). A nonstatistically significant increase in breast cancer-specific mortality rate for women with breast implants relative to surgical controls was observed (HR = 1.32, 95% CI: 0.94-1.83, P = 0.11). No statistically significant differences in stage and breast cancer mortality were observed according to implant characteristics. At diagnosis, breast cancers tended to be at more advanced stages among women with cosmetic breast implants. Breast cancer-specific survival was lower in these women although the reduction did not reach statistical significance. Further investigations of the effect of breast implants on breast cancer prognosis are warranted. 2012 AACR

Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model

PubMed Central

Tice, Jeffrey A.; Cummings, Steven R.; Smith-Bindman, Rebecca; Ichikawa, Laura; Barlow, William E.; Kerlikowske, Karla

2009-01-01

Background Current models for assessing breast cancer risk are complex and do not include breast density, a strong risk factor for breast cancer that is routinely reported with mammography. Objective To develop and validate an easy-to-use breast cancer risk prediction model that includes breast density. Design Empirical model based on Surveillance, Epidemiology, and End Results incidence, and relative hazards from a prospective cohort. Setting Screening mammography sites participating in the Breast Cancer Surveillance Consortium. Patients 1 095 484 women undergoing mammography who had no previous diagnosis of breast cancer. Measurements Self-reported age, race or ethnicity, family history of breast cancer, and history of breast biopsy. Community radiologists rated breast density by using 4 Breast Imaging Reporting and Data System categories. Results During 5.3 years of follow-up, invasive breast cancer was diagnosed in 14 766 women. The breast density model was well calibrated overall (expected–observed ratio, 1.03 [95% CI, 0.99 to 1.06]) and in racial and ethnic subgroups. It had modest discriminatory accuracy (concordance index, 0.66 [CI, 0.65 to 0.67]). Women with low-density mammograms had 5-year risks less than 1.67% unless they had a family history of breast cancer and were older than age 65 years. Limitation The model has only modest ability to discriminate between women who will develop breast cancer and those who will not. Conclusion A breast cancer prediction model that incorporates routinely reported measures of breast density can estimate 5-year risk for invasive breast cancer. Its accuracy needs to be further evaluated in independent populations before it can be recommended for clinical use. PMID:18316752

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women's health initiative

PubMed Central

McGinn, A. P.; Budrys, N.; Chlebowski, R.; Ho, G. Y.; Johnson, K. C.; Lane, D. S.; Li, W.; Neuhouser, M. L.; Saquib, J.; Shikany, J. M.; Song, Y.; Thomson, C.

2014-01-01

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50–79 at enrollment in the women's health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60–0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation. PMID:24104882

Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

PubMed Central

van der Gun, B T F; Huisman, C; Stolzenburg, S; Kazemier, H G; Ruiters, M H J; Blancafort, P; Rots, M G

2013-01-01

Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear. Methods: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain. Results: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival. Conclusion: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer. PMID:23403823

Relationship of Predicted Risk of Developing Invasive Breast Cancer, as Assessed with Three Models, and Breast Cancer Mortality among Breast Cancer Patients

PubMed Central

Pfeiffer, Ruth M.; Miglioretti, Diana L.; Kerlikowske, Karla; Tice, Jeffery; Vacek, Pamela M.; Gierach, Gretchen L.

2016-01-01

Purpose Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown. Methods Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC) for 37,939 invasive breast cancers (1996–2007), we estimated 5-year breast cancer risk (<1%; 1–1.66%; ≥1.67%) with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions); Breast Cancer Risk Assessment Tool (BCRAT); and BCSC 5-year risk model (BCSC-5). Breast cancer-specific mortality post-diagnosis (range: 1–13 years; median: 5.4–5.6 years) was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35–44; 45–54; 55–69; 70–89 years) models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years. Results Of 6,021 deaths, 2,993 (49.7%) were ascribed to breast cancer. In unadjusted case-only analyses, predicted breast cancer risk ≥1.67% versus <1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR) = 0.82 (95% CI = 0.75–0.90); BCRAT: HR = 0.72 (95% CI = 0.65–0.81) and BCSC-5: HR = 0.84 (95% CI = 0.75–0.94). Age-stratified, adjusted models showed similar, although mostly non-significant HRs. Among women ages 55–69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35–44 years. Conclusions Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high predicted risk of developing breast cancer does not imply that if cancer develops it will behave aggressively. PMID:27560501

The Effect of Breast Cancer Fatalism on Breast Cancer Awareness Among Turkish Women.

PubMed

Altintas, Hulya Kulakci; Ayyildiz, Tulay Kuzlu; Veren, Funda; Topan, Aysel Kose

2017-10-01

The aim of this study was to evaluate the effect of breast cancer fatalism and other factors on breast cancer awareness among Turkish women. This cross-sectional and comparative descriptive study was conducted with 894 women. Data were collected by Personal Information Form, Powe Fatalism Inventory and Champion's Health Belief Model Scale. Seriousness, health motivation, BSE benefits and BSE self-efficacy perceptions of the women were moderate, and susceptibility and BSE barriers perceptions were low. It was determined that awareness of breast cancer of the women was affected by breast cancer fatalism, age, education level, employment status, marital status, family type, economic status, social assurance, menopause status, family history of cancer, family history of breast cancer, knowledge on BSE, source of information on BSE, performing of BSE, frequency of BSE performing, having a problem with breast, having a breast examination in hospital, feeling during breast examination by healthcare professional, sex of healthcare professional for breast examination and their health beliefs (p < .05). The results suggested that awareness of breast cancer of the women was affected by breast cancer fatalism. In providing breast cancer early diagnosis behaviors, it is recommended to evaluate fatalism perceptions and health beliefs of the women and to arrange educational programs for this purpose.

POST-TREATMENT REGRET AMONG YOUNG BREAST CANCER SURVIVORS

PubMed Central

Bloom, Joan R.

2010-01-01

Objective The study addresses: (1) what women regret about their breast cancer treatment five years later, and (2) what characteristics of disease and treatment predict post-treatment regret. Method Interviews were conducted with breast cancer survivors in the San Francisco Bay Area. Participants were interviewed following diagnosis. Five years later, women were asked whether they had any regrets about their cancer treatment (N=449). Qualitative analysis was used to identify regret content, and logistic regression was used to determine what characteristics of treatment predicted regret. Results 42.5% of women in the sample regretted some aspect of treatment. The most common regrets were primary surgery (24.1%), chemotherapy and/or radiation (21.5%), reconstruction (17.8%), and problems with providers (13.1%). In addition, women regretted inactions (59.2%) (actions that they did not take) more than actions that they did take (30.4%). This represents a novel finding in the study of post-treatment regret, which has largely focused on regrets over actions. Quantitative analysis revealed that women who were anxious about the future (OR=1.32; p=.03) or had problems communicating with physicians (OR=1.26; p=.02) during treatment were more likely to express regret 5 years later. In addition, women with new or recurrent cancers 5 years later were significantly more likely to regret some aspect of their primary treatment (OR=5.81; p<.001). Conclusion This research supports addressing the psychosocial aspects of cancer care and improving physician-patient communication. Evidence is also provided for addressing the unique emotional needs of women with recurrent cancers, who may experience an undue burden of regret. PMID:20878843

Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

PubMed

Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

Human Papilloma Viruses and Breast Cancer – Assessment of Causality

PubMed Central

Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

Association of ABO and Rh blood groups with breast cancer.

PubMed

Meo, Sultan Ayoub; Suraya, Faryal; Jamil, Badar; Rouq, Fwziah Al; Meo, Anusha Sultan; Sattar, Kamran; Ansari, Mohammad Javed; Alasiri, Saleh A

2017-11-01

The aim of this study was to determine the association of "ABO" and "Rhesus" blood groups with incidence of breast cancer. In this study, we identified 70 research documents from data based search engines including "PubMed", "ISI-Web of Knowledge", "Embase" and "Google Scholar". The research papers were selected by using the primary key-terms including "ABO blood type", "Rhesus" blood type and "breast cancer". The research documents in which "ABO" and "Rhesus" blood types and breast cancer was debated were included. After screening, we reviewed 32 papers and finally we selected 25 research papers which met the inclusion criteria and remaining documents were excluded. Blood group "A" has high incidence of breast cancer (45.88%), blood group "O" has (31.69%); "B" (16.16%) and blood group "AB" has (6.27%) incidence of breast cancer. Blood group "A" has highest and blood group "AB" has least association with breast cancer. Furthermore, "Rhesus +ve" blood group has high incidence of breast cancer (88.31%) and "Rhesus -ve" blood group has least association with breast cancer (11.68%). Blood group "A" and "Rhesus +ve" have high risk of breast cancer, while blood type "AB" and "Rhesus -ve" are at low peril of breast cancer. Physicians should carefully monitor the females with blood group "A" and "Rh +ve" as these females are more prone to develop breast cancer. To reduce breast cancer incidence and its burden, preventive and screening programs for breast cancer especially in young women are highly recommended.

Role of Growth Hormone in Breast Cancer.

PubMed

Subramani, Ramadevi; Nandy, Sushmita B; Pedroza, Diego A; Lakshmanaswamy, Rajkumar

2017-06-01

Breast cancer is one of the most common cancers diagnosed in women. Approximately two-thirds of all breast cancers diagnosed are classified as hormone dependent, which indicates that hormones are the key factors that drive the growth of these breast cancers. Ovarian and pituitary hormones play a major role in the growth and development of normal mammary glands and breast cancer. In particular, the effect of the ovarian hormone estrogen has received much attention in regard to breast cancer. Pituitary hormones prolactin and growth hormone have also been associated with breast cancer. Although the role of these pituitary hormones in breast cancers has been studied, it has not been investigated extensively. In this review, we attempt to compile basic information from most of the currently available literature to understand and demonstrate the significance of growth hormone in breast cancer. Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance. Copyright © 2017 Endocrine Society.

Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

PubMed

Engmann, Natalie J; Golmakani, Marzieh K; Miglioretti, Diana L; Sprague, Brian L; Kerlikowske, Karla

2017-09-01

Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs <30 years). Population-attributable risk proportion of breast cancer. Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense breasts shifted to scattered fibroglandular breast density. Among postmenopausal women, 22.8% (95% CI, 18.3%-27.3%) of breast cancers could potentially be averted if all overweight and obese women attained a body mass index of less than 25. Most women with breast cancer have at least 1 breast cancer risk factor routinely documented at the time of mammography, and more than half of premenopausal and postmenopausal breast cancers are explained by these factors. These easily assessed risk factors should be incorporated into risk prediction models to stratify breast cancer risk and promote risk-based screening and targeted prevention efforts.

Investigation of Three Approaches to Address Fear of Recurrence Among Breast Cancer Survivors

ClinicalTrials.gov

2017-08-16

Breast Neoplasms; Breast Cancer; Breast Carcinoma; Malignant Neoplasm of Breast; Cancer of Breast; Mammary Neoplasm, Human; Human Mammary Carcinoma; Malignant Tumor of Breast; Mammary Cancer; Mammary Carcinoma; Anxiety; Fear; Neoplasm Remission, Spontaneous; Spontaneous Neoplasm Regression; Regression, Spontaneous Neoplasm; Remission, Spontaneous Neoplasm; Spontaneous Neoplasm Remission

Knowledge and perceptions of familial and genetic risks for breast cancer risk in adolescent girls

PubMed Central

Bradbury, Angela R.; Patrick-Miller, Linda; Egleston, Brian L.; Schwartz, Lisa A.; Sands, Colleen B.; Shorter, Rebecca; Moore, Cynthia W.; Tuchman, Lisa; Rauch, Paula; Malhotra, Shreya; Rowan, Brianne; van Decker, Stephanie; Schmidheiser, Helen; Bealin, Lisa; Sicilia, Patrick; Daly, Mary B.

2012-01-01

Background Evidence suggests early events might modify adult breast cancer risk and many adolescents learn of familial and genetic risks for breast cancer. Little is known about how adolescent girls understand and respond to breast cancer risk. Methods Semi-structured interviews with 11-19 year-old girls at high-risk and population-risk for breast cancer evaluated knowledge and perceptions of breast cancer risk and risk modification. Framework analysis and descriptive statistics were utilized to analyze open-ended responses. Risk group and age differences were evaluated by Fisher’s exact and McNemar’s tests. Results 54 girls (86% of invited), 35 high-risk (65%) and 19 population-risk (35%) completed interviews. The most frequently reported risk for breast cancer was family history/hereditary predisposition (66%). Only 17% of girls were aware of BRCA1/2 genes. The majority (76%) of high-risk girls perceive themselves to be at increased risk for breast cancer, compared to 22% of population-risk girls (p=0.001). Half of girls reported that women can get breast cancer before 20 years old. The majority believe there are things women (70%) and girls (67%) can do to prevent breast cancer. Mother was the most frequently reported source of information for breast cancer among both high-risk (97%) and population-risk (89%) girls. Conclusion In this study, many high-risk girls perceive themselves to be at increased risk for breast cancer, and many girls believe that breast cancer can occur in teens. Yet, most girls believe there are things women and girls can do to prevent breast cancer. Research evaluating the impact of awareness and perceptions of breast cancer risk on psychosocial, health and risk behaviors is needed to develop strategies to optimize responses to cancer risk. PMID:23065030

Prevention of ER-Negative Breast Cancer

PubMed Central

Li, Yuxin

2014-01-01

The successful demonstration that the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of breast cancer has stimulated great interest in using drugs to prevent breast cancer in high-risk women. In addition, recent results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective at preventing breast cancer than are SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many estrogen-receptor (ER)-positive breast cancers, these drugs do not prevent the development of ER-negative breast cancer. Thus, there is an urgent need to identify agents that can prevent ER-negative breast cancer. We have studied the cancer preventative activity of several classes of drugs for their ability to prevent ER-negative breast cancer in preclinical models. Results from these studies demonstrate that rexinoids (analogs of retinoids that bind and activate RXR receptors), tyrosine kinase inhibitors (such as EGFR inhibitors and dual kinase inhibitors that block EGFR and HER2/neu signaling), and cyclo-oxygenase 2 (COX-2) inhibitors all prevent ER-negative breast cancer in transgenic mice that develop ER-negative breast cancer. Other promising agents now under investigation include vitamin D and vitamin D analogs, drugs that activate PPAR-gamma nuclear receptors, and statins. Many of these agents are now being tested in early phase cancer prevention clinical trials to determine whether they will show activity in breast tissue and whether they are safe for use in high-risk women without breast cancer. The current status of these studies will be reviewed. It is anticipated that in the future, drugs that effectively prevent ER-negative breast cancer will be used in combination with hormonal agents such SERMs or aromatase inhibitors to prevent all forms of breast cancer. PMID:19213564

Evidence That Breast Tissue Stiffness Is Associated with Risk of Breast Cancer

PubMed Central

Boyd, Norman F.; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J.; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J.; Minkin, Salomon

2014-01-01

Background Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Methods Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. Results After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. Conclusion An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement. PMID:25010427

Breast cancer in men

MedlinePlus

... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

PubMed Central

Haricharan, S; Li, Y

2013-01-01

The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer

PubMed Central

Trabucco, S E; Priedigkeit, N; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-01-01

Abstract Background Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287–395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3′ partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6–7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies. PMID:29360925

CrossLink: a novel method for cross-condition classification of cancer subtypes.

PubMed

Ma, Chifeng; Sastry, Konduru S; Flore, Mario; Gehani, Salah; Al-Bozom, Issam; Feng, Yusheng; Serpedin, Erchin; Chouchane, Lotfi; Chen, Yidong; Huang, Yufei

2016-08-22

We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms.

Breast Cancer awareness among Saudi females in Jeddah.

PubMed

Radi, Sahar Mahmoud

2013-01-01

Breast cancer is the most frequent malignancy of women worldwide. It is the leading cause of female cancer related disability and mortality. In Saudi Arabia breast cancer ranks first among cancerous diseases in females. In the Gulf region, and especially in Saudi Arabia, few studies have been conducted to address breast cancer awareness. The purpose of the current study was therefore to investigate the level of breast cancer awareness among Saudi females in Jeddah, focusing on knowledge of breast cancer warning signs, risk factors, screening programs and breast self-examination (BSE). The design of this study was an exploratory correlational analysis. The sample comprised 200 Saudi females aged 20 and older living in Jeddah. Data were collected using face-to- face interviews. Breast cancer awareness was measured using a modified Arabic version of the Breast Cancer Awareness Measure (Breast CAM) version 2. Descriptive statistical analysis, Pearson's Product Moment correlation coefficients and ANOVA test were used to answer study questions. Out of 200 participants, 50.5% were aware of breast lump as a warning sign of breast cancer, 57.5% claimed that family history was risk factor, 20.5% had undergone breast screening, 79% heard about BSE, and 47.5% knew how to perform BSE. Findings indicated that Saudi females level of awareness of breast cancer is very inadequate. Public awareness interventions are needed in order to overcome an ever-increasing burden of this disease among Saudi females.

CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer

PubMed Central

Weischer, Maren; Nordestgaard, Børge G.; Pharoah, Paul; Bolla, Manjeet K.; Nevanlinna, Heli; van't Veer, Laura J.; Garcia-Closas, Montserrat; Hopper, John L.; Hall, Per; Andrulis, Irene L.; Devilee, Peter; Fasching, Peter A.; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G.; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J.; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M.; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M.; Wang, Qin; Muranen, Taru A.; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C.; Czene, Kamila; Knight, Julia A.; Tollenaar, Rob A.E.M.; Beckmann, Matthias W.; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W.R.; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E.; Kosma, Veli-Matti; Kristensen, Vessela N.; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B.; Leunen, Karin; Kriege, Mieke; Cross, Simon S.; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F.; Schmidt, Marjanka K.; Bojesen, Stig E.

2012-01-01

Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer–specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer–specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor–positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer–specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor–positive first breast cancer only. Conclusion Among women with estrogen receptor–positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer–specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer. PMID:23109706

HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models.

PubMed

Whitesell, Luke; Santagata, Sandro; Mendillo, Marc L; Lin, Nancy U; Proia, David A; Lindquist, Susan

2014-12-23

The efficacy of hormonal therapies for advanced estrogen receptor-positive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.

What Factors Influence Women's Perceptions of their Systemic Recurrence Risk after Breast Cancer Treatment?

PubMed

Lee, Kamaria L; Janz, Nancy K; Zikmund-Fisher, Brian J; Jagsi, Reshma; Wallner, Lauren P; Kurian, Allison W; Katz, Steven J; Abrahamse, Paul; Hawley, Sarah T

2018-01-01

Breast cancer patients' misunderstanding of their systemic cancer recurrence risk has consequences on decision-making and quality of life. Little is known about how women derive their risk estimates. Using Los Angeles and Georgia's SEER registries (2014-2015), a random sample of early-stage breast cancer patients was sent surveys about 2 to 3 months after surgery ( N = 3930; RR, 68%). We conducted an inductive thematic analysis of open-ended responses about why women chose their risk estimates in a uniquely large sub-sample ( N = 1,754). Clinician estimates of systemic recurrence risk were provided for patient sub-groups with DCIS and with low-, intermediate-, and high-risk invasive disease. Women's perceived risk of systemic recurrence (0% to 100%) was categorized as overestimation, reasonably accurate estimation, or underestimation (0% for invasive disease) and was compared across identified factors and by clinical presentation. Women identified 9 main factors related to their clinical experience (e.g., diagnosis and testing; treatment) and non-clinical beliefs (e.g., uncertainty; spirituality). Women who mentioned at least one clinical experience factor were significantly less likely to overestimate their risk (12% v. 43%, P < 0.001). Most women who were influenced by "communication with a clinician" had reasonably accurate recurrence estimates (68%). "Uncertainty" and "family and personal history" were associated with overestimation, particularly for women with DCIS (75%; 84%). "Spirituality, religion, and faith" was associated with an underestimation of risk (63% v. 20%, P < 0.001). The quantification of our qualitative results is subject to any biases that may have occurred during the coding process despite rigorous methodology. Patient-clinician communication is important for breast cancer patients' understanding of their numeric risk of systemic recurrence. Clinician discussions about recurrence risk should address uncertainty and relevance of family and personal history.

Breast cancer and protein biomarkers

PubMed Central

Gam, Lay-Harn

2012-01-01

Breast cancer is a healthcare concern of women worldwide. Despite procedures being available for diagnosis, prognosis and treatment of breast cancer, researchers are working intensively on the disease in order to improve the life quality of breast cancer patients. At present, there is no single treatment known to bring a definite cure for breast cancer. One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection, prognosis and treatments of the cancer. Therefore, the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide. PMID:24520539

An anatomically oriented breast model for MRI

NASA Astrophysics Data System (ADS)

Kutra, Dominik; Bergtholdt, Martin; Sabczynski, Jörg; Dössel, Olaf; Buelow, Thomas

2015-03-01

Breast cancer is the most common cancer in women in the western world. In the breast cancer care-cycle, MRIis e.g. employed in lesion characterization and therapy assessment. Reading of a single three dimensional image or comparing a multitude of such images in a time series is a time consuming task. Radiological reporting is done manually by translating the spatial position of a finding in an image to a generic representation in the form of a breast diagram, outlining quadrants or clock positions. Currently, registration algorithms are employed to aid with the reading and interpretation of longitudinal studies by providing positional correspondence. To aid with the reporting of findings, knowledge about the breast anatomy has to be introduced to translate from patient specific positions to a generic representation. In our approach we fit a geometric primitive, the semi-super-ellipsoid to patient data. Anatomical knowledge is incorporated by fixing the tip of the super-ellipsoid to the mammilla position and constraining its center-point to a reference plane defined by landmarks on the sternum. A coordinate system is then constructed by linearly scaling the fitted super-ellipsoid, defining a unique set of parameters to each point in the image volume. By fitting such a coordinate system to a different image of the same patient, positional correspondence can be generated. We have validated our method on eight pairs of baseline and follow-up scans (16 breasts) that were acquired for the assessment of neo-adjuvant chemotherapy. On average, the location predicted and the actual location of manually set landmarks are within a distance of 5.6 mm. Our proposed method allows for automatic reporting simply by uniformly dividing the super-ellipsoid around its main axis.

A unique hypofractionated radiotherapy schedule with 51.3 Gy in 18 fractions three times per week for early breast cancer: outcomes including local control, acute and late skin toxicity.

PubMed

Vassilis, Kouloulias; Ioannis, Gogalis; Anna, Zygogianni; Christina, Armpilia; Christos, Antypas; John, Kokakis; Porfyrios, Koromperlis; Vassiliki, Gennimata; John, Kouvaris

2017-03-01

Evaluation of local control and acute and late toxicity regarding a hypofractionated RT schedule for breast cancer patients. Between October 2007 and October 2009, 80 women with early breast cancer were treated by 42.75 Gy in 15 fractions over 5 weeks. This treatment involved three fractions per week (Monday-Wednesday-Friday). All patients received an additional boost dose to the tumor bed of 8.55 Gy in 3 fractions using 6 MV photons. The primary endpoint included any local recurrence in the treated breast. Secondary endpoint included acute and late radiation skin toxicity. The median follow-up time was 63 months (range 60-72). Radiation toxicity was graded according the RTOG/EORTC criteria. Neither local nor distant recurrence was noted in any patient during this 3-year follow-up. Grade 0, 1, 2 acute skin toxicity was observed in 56/80 (70.0 %), in 19/80 (23.8 %) and in 5/80 (6.3 %), respectively. Three months post-RT, toxicity grades 0, 1, 2 skin toxicity were 64/80 (80 %), 14/80 (17.5 %) and 2/80 (2.5 %), respectively. Late toxicity as grade 0, 1 was observed in 72/80 (90.0 %) and in 8/80 (10.0 %), respectively, 6 months post-RT, whereas after 1 year they were 78/80 (97.5 %) and 2/80 (2.5 %), respectively. Preliminary results regarding skin reactions, cosmetic appearance and local control are consistent with published data that support the use of shorter fractionation schedules in early breast cancer patients after breast conservative surgery. Longer follow-up and a randomized prospective study stand in need for the extraction of safe conclusions.

Targeted Therapy for Breast Cancer Prevention

PubMed Central

den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

2013-01-01

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

A novel isoform of TET1 that lacks a CXXC domain is overexpressed in cancer

PubMed Central

Good, Charly R.; Madzo, Jozef; Patel, Bela; Maegawa, Shinji; Engel, Nora; Jelinek, Jaroslav

2017-01-01

Abstract TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation, but it also limits its ability to regulate genes outside of CGIs. Here, we report a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site. Importantly, TET1ALT lacks the CXXC domain but retains the catalytic domain. TET1ALT is repressed in embryonic stem cells (ESCs) but becomes activated in embryonic and adult tissues while TET1FL is expressed in ESCs, but repressed in adult tissues. Overexpression of TET1ALT shows production of 5hmC with distinct (and weaker) effects on DNA methylation or gene expression when compared to TET1FL. TET1ALT is aberrantly activated in multiple cancer types including breast, uterine and glioblastoma, and TET1 activation is associated with a worse overall survival in breast, uterine and ovarian cancers. Our data suggest that the predominantly activated isoform of TET1 in cancer cells does not protect from CGI methylation and likely mediates dynamic site-specific demethylation outside of CGIs. PMID:28531272

Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Hongsheng; Wu, Fenping; Wang, Yan

2014-08-08

Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found thatmore » Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.« less

Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

PubMed

Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2016-01-01

The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

Do Structural Missense Variants in the ATM Gene Found in Women With Breast Cancer Cause Breast Cancer in Knock-in Mouse Strains?

DTIC Science & Technology

2006-04-01

W81XWH-05-1-0282 TITLE: Do Structural Missense Variants in the ATM Gene Found in Women with Breast Cancer Cause Breast Cancer in "Knock-in...5a. CONTRACT NUMBER Do Structural Missense Variants in the ATM Gene Found in Women with Breast Cancer Cause Breast Cancer in "Knock-in" Mouse...human cohort-specific missense mutations will develop breast cancer with dominant inheritance in a subset of animals. It also is hypothesized that

Breast reconstruction after mastectomy at a comprehensive cancer center.

PubMed

Connors, Shahnjayla K; Goodman, Melody S; Myckatyn, Terence; Margenthaler, Julie; Gehlert, Sarah

2016-01-01

Breast reconstruction after mastectomy is an integral part of breast cancer treatment that positively impacts quality of life in breast cancer survivors. Although breast reconstruction rates have increased over time, African American women remain less likely to receive breast reconstruction compared to Caucasian women. National Cancer Institute-designated Comprehensive Cancer Centers, specialized institutions with more standardized models of cancer treatment, report higher breast reconstruction rates than primary healthcare facilities. Whether breast reconstruction disparities are reduced for women treated at comprehensive cancer centers is unclear. The purpose of this study was to further investigate breast reconstruction rates and determinants at a comprehensive cancer center in St. Louis, Missouri. Sociodemographic and clinical data were obtained for women who received mastectomy for definitive surgical treatment for breast cancer between 2000 and 2012. Logistic regression was used to identify factors associated with the receipt of breast reconstruction. We found a breast reconstruction rate of 54 % for the study sample. Women who were aged 55 and older, had public insurance, received unilateral mastectomy, and received adjuvant radiation therapy were significantly less likely to receive breast reconstruction. African American women were 30 % less likely to receive breast reconstruction than Caucasian women. These findings suggest that racial disparities in breast reconstruction persist in comprehensive cancer centers. Future research should further delineate the determinants of breast reconstruction disparities across various types of healthcare institutions. Only then can we develop interventions to ensure all eligible women have access to breast reconstruction and the improved quality of life it affords breast cancer survivors.

Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

ClinicalTrials.gov

2017-11-22

Solid Neoplasm; Stage III Pancreatic Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Sarcoma; Colorectal Cancer; Head and Neck Cancer; Cancer of Unknown Primary; Bladder Cancer; Ovarian Cancer

[The clinical study of familial breast cancer - now and the problems].

PubMed

Nomizu, Tadashi; Matsuzaki, Masami; Katagata, Naoto; Watanabe, Fumiaki; Akama, Yoshinori

2012-04-01

The clinical features of familial breast cancer are characterized by early onset, high frequency of bilateral breast cancer, and multiple malignancies of other organs. It is strongly suggested that genetic factors contribute to familial breast cancer. The causative genes now identified are BRCA1 and BRCA2. This disease is called hereditary breast ovarian cancer syndrome (HBOC)because breast cancer and ovarian cancer are clustered in the kindred confirmed BRCA mutation. As for BRCA related breast cancer, early onset and highly frequent bilateral breast cancer are characteristic. In addition, the histological grade is high and the positive rate of estrogen receptors is low in BRCA1-related breast cancer. Gene diagnosis of BRCA is useful when choosing a surgical method, chemotherapy, or a surveillance of mutation carriers. The problem in Japan is that the treatment is very expensive, with poor understanding of HBOC of by clinicians and as yet immature genetic counseling system.

Breast Cancer Knowledge and Early Detection among Hispanic Women with a Family History of Breast Cancer along the U.S.-Mexico Border

PubMed Central

Bird, Yelena; Moraros, John; Banegas, Matthew P.; King, Sasha; Prapasiri, Surasri; Thompson, Beti

2013-01-01

Background Breast cancer is the leading cause of cancer-related death among U.S. Hispanic women. Hispanics are less likely than non-Hispanic White women to be diagnosed at an early stage and survive breast cancer. Methods For this cross-sectional study, we assessed differences in breast cancer knowledge, attitudes, and screening practices between Hispanic women with (FH+) and without (FH−) a family history of breast cancer in three U.S.-Mexico border counties. Results Among 137 Hispanic women age 40 and older, FH+ women had levels of knowledge and attitudes about breast cancer similar to those of FH− women. FH+ participants were more likely to have ever performed breast self-examinations, although levels of compliance with screening guidelines did not significantly differ between FH+ and FH− groups. Conclusion U.S. Hispanic women with a family history of breast cancer constitute an at-risk group for which adhering to preventive screening guidelines could substantially reduce breast cancer mortality. PMID:20453351

Descriptive characteristics of prostate cancer in patients with a history of primary male breast cancer - a SEER analysis.

PubMed

Abhyankar, Nikita; Hoskins, Kent F; Abern, Michael R; Calip, Gregory S

2017-09-25

Current evidence on risk of prostate cancer following a diagnosis of male breast cancer is limited and guidance for screening in this potentially higher-risk population remainsunclear. Our objective was to quantify prostate cancer risk in men diagnosed with breast cancer. We identified men diagnosed with first primary breast cancer between 1988 and 2012 using the Surveillance, Epidemiology and End Results Program registry databases. Men were followed for occurrence of a second primary prostate cancer and secondary outcomes of cancer-specific and overall survival. Stratified analyses were performed by age, breast cancer stage, race, and breast cancer hormone receptor status. Excess risk per 10,000 person-years and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were calculated. We used multivaraible Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for characteristics associated with secondary prostate cancer and survival. From a cohort of 5753 men with breast cancer with median follow up of 4.3 years, we identified 250 cases of second primary prostate cancer. Overall, the incidence of second primary prostate cancer was modestly greater than expected (SIR = 1.12, 95% CI 0.93-1.33), although not statistically significant. Stratified analyses demonstrated associations for men ages 65-74 at the time of breast cancer diagnosis (SIR = 1.34, 95%CI 1.01-1.73), hormone receptor-positive breast cancer (SIR = 1.23, 95%CI 1.11-1.39) or AJCC stage I breast cancer (SIR = 1.36, 95%CI 1.04-1.75) and second primary prostate cancer diagnosis. The incidence of prostate cancer in men with history of breast cancer is similar to the general population. Men with favorable characteristics of their breast cancer were more likely to develop prostate cancer, possibly due to a lower competing risk of breast cancer mortality.

Elevated S100A8 protein expression in breast cancer cells and breast tumor stroma is prognostic of poor disease outcome.

PubMed

Miller, P; Kidwell, K M; Thomas, D; Sabel, M; Rae, J M; Hayes, D F; Hudson, B I; El-Ashry, D; Lippman, M E

2017-11-01

Elevated S100A8 expression has been observed in cancers of the bladder, esophagus, colon, ovary, and breast. S100A8 is expressed by breast cancer cells as well as by infiltrating immune and myeloid cells. Here we investigate the association of elevated S100A8 protein expression in breast cancer cells and in breast tumor stroma with survival outcomes in a cohort of breast cancer patients. Tissue microarrays (TMA) were constructed from breast cancer specimens from 417 patients with stage I-III breast cancer treated at the University of Michigan Comprehensive Cancer Center between 2004 and 2006. Representative regions of non-necrotic tumor and distant normal tissue from each patient were used to construct the TMA. Automated quantitative immunofluorescence (AQUA) was used to measure S100A8 protein expression, and samples were scored for breast cancer cell and stromal S100A8 expression. S100A8 staining intensity was assessed as a continuous value and by exploratory dichotomous cutoffs. Associations between breast cancer cell and stromal S100A8 expression with disease-free survival and overall survival were determined using the Kaplan-Meier method and Cox proportional hazard models. High breast cancer cell S100A8 protein expression (as indicated by AQUA scores), as a continuous measure, was a significant prognostic factor for OS [univariable hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.00-1.55, p = 0.05] in this patient cohort. Exploratory analyses identified optimal S100A8 AQUA score cutoffs within the breast cancer cell and stromal compartments that significantly separated survival curves for the complete cohort. Elevated breast cancer cell and stromal S100A8 expression, indicated by higher S100A8 AQUA scores, significantly associates with poorer breast cancer outcomes, regardless of estrogen receptor status. Elevated breast cancer cell and stromal S1008 protein expression are significant indicators of poorer outcomes in early stage breast cancer patients. Evaluation of S100A8 protein expression may provide additional prognostic information beyond traditional breast cancer prognostic biomarkers.

Molecular biology of breast cancer stem cells: potential clinical applications.

PubMed

Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

Nested Nanotherapeutics for Drug Synergy Enhancement in Breast Cancer Therapy

DTIC Science & Technology

2014-09-01

completion of the proposed aims has resulted in the development of a truly innovative nanoparticle platform for synergistic enhancement in breast cancer ...of nested nanoparticles and intracellular release in MCF-7 breast cancer cells. a. Confocal microscopy of MCF-7 breast cancer cells at... nanoparticle accumulation over time in MCF-7 breast cancer cells. d. Mean fluorescence intensity over time in MCF-7 breast cancer cells as determined by

Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models

PubMed Central

Suarez-Arroyo, Ivette J.; Rosario-Acevedo, Raysa; Aguilar-Perez, Alexandra; Clemente, Pedro L.; Cubano, Luis A.; Serrano, Juan; Schneider, Robert J.; Martínez-Montemayor, Michelle M.

2013-01-01

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers. PMID:23468988

Anti-tumor effects of Ganoderma lucidum (reishi) in inflammatory breast cancer in in vivo and in vitro models.

PubMed

Suarez-Arroyo, Ivette J; Rosario-Acevedo, Raysa; Aguilar-Perez, Alexandra; Clemente, Pedro L; Cubano, Luis A; Serrano, Juan; Schneider, Robert J; Martínez-Montemayor, Michelle M

2013-01-01

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

Alternative therapies for metastatic breast cancer: multimodal approach targeting tumor cell heterogeneity.

PubMed

Sambi, Manpreet; Haq, Sabah; Samuel, Vanessa; Qorri, Bessi; Haxho, Fiona; Hill, Kelli; Harless, William; Szewczuk, Myron R

2017-01-01

One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

"Voices of fear and safety" women's ambivalence towards breast cancer and breast health: a qualitative study from Jordan.

PubMed

Taha, Hana; Al-Qutob, Raeda; Nyström, Lennarth; Wahlström, Rolf; Berggren, Vanja

2012-07-26

Breast cancer is the leading cause of cancer mortality among Jordanian women. Breast malignancies are detected at late stages as a result of deferred breast health-seeking behaviour. The aim of this study was to explore Jordanian women's views and perceptions about breast cancer and breast health. We performed an explorative qualitative study with purposive sampling. Ten focus groups were conducted consisting of 64 women (aged 20 to 65 years) with no previous history and no symptoms of breast cancer from four governorates in Jordan. The transcribed data was analysed using latent content analysis. Three themes were constructed from the group discussions: a) Ambivalence in prioritizing own health; b) Feeling fear of breast cancer; and c) Feeling safe from breast cancer. The first theme was seen in women's prioritizing children and family needs and in their experiencing family and social support towards seeking breast health care. The second theme was building on women's perception of breast cancer as an incurable disease associated with suffering and death, their fear of the risk of diminished femininity, husband's rejection and social stigmatization, adding to their apprehensions about breast health examinations. The third theme emerged from the women's perceiving themselves as not being in the risk zone for breast cancer and in their accepting breast cancer as a test from God. In contrast, women also experienced comfort in acquiring breast health knowledge that soothed their fears and motivated them to seek early detection examinations. Women's ambivalence in prioritizing their own health and feelings of fear and safety could be better addressed by designing breast health interventions that emphasize the good prognosis for breast cancer when detected early, involve breast cancer survivors in breast health awareness campaigns and catalyse family support to encourage women to seek breast health care.

“Voices of Fear and Safety” Women’s ambivalence towards breast cancer and breast health: a qualitative study from Jordan

PubMed Central

2012-01-01

Background Breast cancer is the leading cause of cancer mortality among Jordanian women. Breast malignancies are detected at late stages as a result of deferred breast health-seeking behaviour. The aim of this study was to explore Jordanian women’s views and perceptions about breast cancer and breast health. Methods We performed an explorative qualitative study with purposive sampling. Ten focus groups were conducted consisting of 64 women (aged 20 to 65 years) with no previous history and no symptoms of breast cancer from four governorates in Jordan. The transcribed data was analysed using latent content analysis. Results Three themes were constructed from the group discussions: a) Ambivalence in prioritizing own health; b) Feeling fear of breast cancer; and c) Feeling safe from breast cancer. The first theme was seen in women’s prioritizing children and family needs and in their experiencing family and social support towards seeking breast health care. The second theme was building on women’s perception of breast cancer as an incurable disease associated with suffering and death, their fear of the risk of diminished femininity, husband’s rejection and social stigmatization, adding to their apprehensions about breast health examinations. The third theme emerged from the women’s perceiving themselves as not being in the risk zone for breast cancer and in their accepting breast cancer as a test from God. In contrast, women also experienced comfort in acquiring breast health knowledge that soothed their fears and motivated them to seek early detection examinations. Conclusions Women’s ambivalence in prioritizing their own health and feelings of fear and safety could be better addressed by designing breast health interventions that emphasize the good prognosis for breast cancer when detected early, involve breast cancer survivors in breast health awareness campaigns and catalyse family support to encourage women to seek breast health care. PMID:22834874

Management of hereditary breast and ovarian cancer.

PubMed

Yamauchi, Hideko; Takei, Junko

2018-02-01

Hereditary breast and ovarian cancer (HBOC) syndrome represents 5-10% of all breast cancers. In Japan, the HBOC syndrome is frequently diagnosed in patients with breast cancer. Therefore, a treatment strategy combining a plan for existing breast cancer and for reduction of future breast and ovarian cancer risk is necessary. Breast cancer risk-reducing management involves three options-surveillance, chemoprevention, and risk-reducing mastectomy (RRM). RRM can prevent >90% of new breast cancers. Ovarian cancer risk management options are more limited, and risk-reduction salpingo-oophorectomy is the only option since there is no proven effective early detection method available. The local recurrence rate following breast-conserving surgery in BRCA1/2 mutation-associated breast cancer is not significantly higher than that in sporadic breast cancer. Furthermore, there is no difference in prognosis between surgical methods. Clinicians should inform patients that there are no data on long-term monitoring and fully discuss risks of re-developing breast cancer with patients when choosing the surgical method. In HBOC, BRCA1/2 mutations lead to failure of double-strand DNA break repair, with poly ADP-ribose polymerase (PARP) playing an important role in single-strand DNA nick repair. Use of PARP inhibitors in HBOC prevents DNA repair (synthetic lethality) leading to cell death. This review summarizes management of the HBOC syndrome based on recent evidence.