Radiation therapy in early-stage invasive breast cancer.

PubMed

Lin, Ray; Tripuraneni, Prabhakar

2011-06-01

The treatment of breast cancer involves a multi-disciplinary approach with radiation therapy playing a key role. Breast-conserving surgery has been an option for women with early-stage breast cancer for over two decades now. Multiple randomized trials now have demonstrated the efficacy of breast-conserving surgery followed by radiation therapy. With the advancements in breast imaging and the successful campaign for early detection of breast cancer, more women today are found to have early-stage small breast cancers. Patient factors (breast size, tumor location, history of prior radiation therapy, preexisting conditions such as collagen vascular disease, age, having prosthetically augmented breasts), pathological factors (margin status, tumor size, presence of extensive intraductal component requiring multiple surgical excisions), as well as patient preference are all taken into consideration prior to surgical management of breast cancer. Whole-breast fractionated radiation therapy between 5 and 7 weeks is considered as the standard of care treatment following breast-conserving surgery. However, new radiation treatment strategies have been developed in recent years to provide alternatives to the conventional 5-7 week whole-breast radiation therapy for some patients. Accelerated partial breast radiation therapy (APBI) was introduced because the frequency of breast recurrences outside of the surgical cavity has been shown to be low. This technique allows treatments to be delivered quicker (usually 1 week, twice daily) to a limited volume. Often times, this treatment involves the use of a brachytherapy applicator to be placed into the surgical cavity following breast-conserving surgery. Accelerated hypofractionated whole-breast irradiation may be another faster way to deliver radiation therapy following breast-conserving surgery. This journal article reviews the role of radiation therapy in women with early-stage breast cancer addressing patient selection in breast

FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation.

PubMed

Zhou, H; Liu, Y; Zhu, R; Ding, F; Wan, Y; Li, Y; Liu, Z

2017-06-08

Krüppel-like factor 4 (KLF4, GKLF) is a zinc-finger transcription factor involved in a large variety of cellular processes, including apoptosis, cell cycle progression, as well as stem cell renewal. KLF4 is critical for cell fate decision and has an ambivalent role in tumorigenesis. Emerging data keep reminding us that KLF4 dysregulation either facilitates or impedes tumor progression, making it important to clarify the regulating network of KLF4. Like most transcription factors, KLF4 has a rather short half-life within the cell and its turnover must be carefully orchestrated by ubiquitination and ubiquitin-proteasome system. To better understand the mechanism of KLF4 ubiquitination, we performed a genome-wide screen of E3 ligase small interfering RNA library based on western blot and identified SCF-FBXO32 to be a new E3 ligase, which is responsible for KLF4 ubiquitination and degradation. The F-box domain is critical for FBXO32-dependent KLF4 ubiquitination and degradation. Furthermore, we demonstrated that FBXO32 physically interacts with the N-terminus (1-60 aa) of KLF4 via its C-terminus (228-355 aa) and directly targets KLF4 for ubiquitination and degradation. We also found out that p38 mitogen-activated protein kinase pathway may be implicated in FBXO32-mediated ubiquitination of KLF4, as p38 kinase inhibitor coincidently abrogates endogenous KLF4 ubiquitination and degradation, as well as FBXO32-dependent exogenous KLF4 ubiquitination and degradation. Finally, FBXO32 inhibits colony formation in vitro and primary tumor initiation and growth in vivo through targeting KLF4 into degradation. Our findings thus further elucidate the tumor-suppressive function of FBXO32 in breast cancer. These results expand our understanding of the posttranslational modification of KLF4 and of its role in breast cancer development and provide a potential target for diagnosis and therapeutic treatment of breast cancer.

Assessment of palindromes as platforms for DNA amplification in breast cancer

PubMed Central

Guenthoer, Jamie; Diede, Scott J.; Tanaka, Hisashi; Chai, Xiaoyu; Hsu, Li; Tapscott, Stephen J.; Porter, Peggy L.

2012-01-01

DNA amplification, particularly of chromosomes 8 and 11, occurs frequently in breast cancer and is a key factor in tumorigenesis, often associated with poor prognosis. The mechanisms involved in the amplification of these regions are not fully understood. Studies from model systems have demonstrated that palindrome formation can be an early step in DNA amplification, most notably seen in the breakage–fusion–bridge (BFB) cycle. Therefore, palindromes might be associated with gene amplicons in breast cancer. To address this possibility, we coupled high-resolution palindrome profiling by the Genome-wide Analysis of Palindrome Formation (GAPF) assay with genome-wide copy-number analyses on a set of breast cancer cell lines and primary tumors to spatially associate palindromes and copy-number gains. We identified GAPF-positive regions distributed nonrandomly throughout cell line and tumor genomes, often in clusters, and associated with copy-number gains. Commonly amplified regions in breast cancer, chromosomes 8q and 11q, had GAPF-positive regions flanking and throughout the copy-number gains. We also identified amplification-associated GAPF-positive regions at similar locations in subsets of breast cancers with similar characteristics (e.g., ERBB2 amplification). These shared positive regions offer the potential to evaluate the utility of palindromes as prognostic markers, particularly in premalignant breast lesions. Our results implicate palindrome formation in the amplification of regions with key roles in breast tumorigenesis, particularly in subsets of breast cancers. PMID:21752925

G protein-coupled estrogen receptor (GPER) regulates mammary tumorigenesis and metastasis

PubMed Central

Marjon, Nicole A.; Hu, Chelin

2014-01-01

The role of 17β-estradiol (E2) in breast cancer development and tumor growth has traditionally been attributed exclusively to the activation of ERα. Although targeted inhibition of ERα is a successful approach for patients with ERα+ breast cancer, many patients fail to respond or become resistant to anti-estrogen therapy. The discovery of the G protein-coupled estrogen receptor (GPER1) suggested an additional mechanism through which E2 could exert its effects in breast cancer. Studies have demonstrated clinical correlations between GPER expression in human breast tumor specimens and increased tumor size, distant metastasis, and recurrence, as well as established a proliferative role for GPER in vitro; however, direct in vivo evidence has been lacking. To this end, a GPER null mutation [GPER knockout (KO)] was introduced, through interbreeding, into a widely used transgenic mouse model of mammary tumorigenesis [MMTV-PyMT (PyMT)]. Early tumor development, assessed by the extent of hyperplasia and proliferation, was not different between GPER wild-type/PyMT (WT/PyMT) and those mice harboring the GPER null mutation (KO/PyMT). However, by 12-13 weeks of age, tumors from KO/PyMT mice were smaller with decreased proliferation compared to those from WT/PyMT mice. Furthermore, tumors from the KO/PyMT mice were of histologically lower grade compared to tumors from their WT counterparts, suggesting less aggressive tumors in the KO/PyMT mice. Finally, KO/PyMT mice displayed dramatically fewer lung metastases compared to WT/PyMT mice. Combined, these data provide the first in vivo evidence that GPER plays a critical role in breast tumor growth and distant metastasis. PMID:25030371

Blood-Based Biomarkers of Early-Onset Breast Cancer

DTIC Science & Technology

2015-10-01

n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

PubMed

Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

2015-05-01

Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exercise Effects on Tumorigenesis in a p53-deficient Mouse Model of Breast Cancer

PubMed Central

Colbert, Lisa H.; Westerlind, Kim C.; Perkins, Susan N.; Haines, Diana C.; Berrigan, David; Donehower, Lawrence A.; Fuchs-Young, Robin; Hursting, Stephen D.

2011-01-01

Purpose Physically active women have a reduced risk of breast cancer, but the dose of activity necessary and the role of energy balance and other potential mechanisms have not been fully explored in animal models. We examined treadmill and wheel running effects on mammary tumorigenesis and biomarkers in p53-deficient (p53+/−): MMTV-Wnt-1 transgenic mice. Methods Female mice (9 wks old) were randomly assigned to the following groups in Experiment 1: treadmill exercise 5 d/wk, 45 min/d, 5% grade at 20 m/min, ~0.90 km/d (TREX1, n=20); at 24 m/min, ~1.08 km/d (TREX2, n=21); or a non-exercise control (CON-TREX, n=22). In Experiment 2, mice were randomly assigned to voluntary wheel-running (WHL, n=21, 2.46 ± 1.11 km/d (mean ± SD)) or a non-exercise control (CON-WHL, n=22). Body composition was measured at ~9 weeks and serum insulin-like growth factor-1 (IGF-1) at 2–3 monthly time points beginning at ~9 weeks on study. Mice were sacrificed when tumors reached 1.5 cm, mice became moribund, or there was only one mouse per treatment group remaining. Results TREX1 (24 wks) and TREX2 (21 wks) had shorter survival median survival times than CON-TREX (34 wks; p<0.01); WHL and CON-WHL survival was similar (23 vs. 24 wks; p=0.32). TREX2 had increased multiplicity of mammary gland carcinomas compared to CON-TREX; WHL had a higher tumor incidence than CON-WHL. All exercising animals were lighter than their respective controls, and WHL had lower body fat than CON-WHL (p<0.01). There was no difference in IGF-1 between groups (p>0.05). Conclusion Despite beneficial or no effects on body weight, body fat, or IGF-1, exercise had detrimental effects on tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer. PMID:19568200

Partial breast radiation for early-stage breast cancer.

PubMed

McCormick, Beryl

2012-02-01

This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.

Breast cancer risk accumulation starts early: prevention must also.

PubMed

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S

2014-06-01

Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman's long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors is related to breast cancer risk and risk of premalignant proliferative benign lesions. Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention.

Automated System for Early Breast Cancer Detection in Mammograms

NASA Technical Reports Server (NTRS)

Bankman, Isaac N.; Kim, Dong W.; Christens-Barry, William A.; Weinberg, Irving N.; Gatewood, Olga B.; Brody, William R.

1993-01-01

The increasing demand on mammographic screening for early breast cancer detection, and the subtlety of early breast cancer signs on mammograms, suggest an automated image processing system that can serve as a diagnostic aid in radiology clinics. We present a fully automated algorithm for detecting clusters of microcalcifications that are the most common signs of early, potentially curable breast cancer. By using the contour map of the mammogram, the algorithm circumvents some of the difficulties encountered with standard image processing methods. The clinical implementation of an automated instrument based on this algorithm is also discussed.

Toward a clinically useful method of predicting early breast-feeding attrition.

PubMed

Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

2006-08-01

The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

Dendritic Cells Program Non-Immunogenic Prostate-Specific T Cell Responses Beginning at Early Stages of Prostate Tumorigenesis

PubMed Central

Mihalyo, Marianne A.; Hagymasi, Adam T.; Slaiby, Aaron M.; Nevius, Erin E.; Adler, Adam J.

2010-01-01

BACKGROUND Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4+CD25+ T regulatory cells (Tregs) in programming tolerance. METHODS The response of naïve HA-specific CD4+ T cells were analyzed following adoptive transfer into Pro-HA × TRAMP transgenic mice harboring variably-staged HA-expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA-specific CD4 cell responses were assessed via depletion. RESULTS HA-specific CD4 cells underwent non-immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS These results suggest that tolerogenicity is an early and general property of prostate tumors. PMID:17221844

Expressive writing in early breast cancer survivors.

PubMed

Craft, Melissa A; Davis, Gail C; Paulson, René M

2013-02-01

This article is the report of a study aimed at determining whether or not expressive writing improves the quality-of-life of early breast cancer survivors. An additional aim is the investigation of whether or not the type of writing prompt makes a difference in results. The risk of distress can extend well beyond the time of a breast cancer diagnosis. Emotional expression may assist in dealing with this. Randomized controlled study. Participants (n = 120) were randomized into one of four groups: a control group (no writing) or one of three expressive writing groups: breast cancer trauma, any self-selected trauma and facts related to breast cancer. Participants wrote 20 minutes a day for 4 consecutive days. Their quality-of-life was measured, using the 'Functional Assessment of Cancer Therapy-Breast Cancer Version', at baseline and at 1 month and 6 months after writing. Paired t-tests, multivariate analysis of variance and multiple regression were used to analyse the data of the 97 participants who completed the journaling assignment and at least the first assessment, collected in 2006. Intention-to-treat analysis was used. Expressive writing about one's breast cancer, breast cancer trauma and facts related to breast cancer, significantly improved the quality-of-life outcome. Expressive writing, focusing the instructions on writing about one's living and dealing with a diagnosis of breast cancer, is recommended for early breast cancer survivors as a feasible and easily implemented treatment approach to improve quality-of-life. © 2012 Blackwell Publishing Ltd.

[Selection criteria for breast conservation in patients with early breast carcinoma].

PubMed

Baĭchev, G

2002-01-01

During the past two decades, breast-conserving therapy (excision of the tumor and axillary lymphadenectomy followed by irradiation) for early stage breast carcinoma has become firmly established as an equivalent treatment approach to mastectomy. The purpose of this review as to examine the risk factors for local recurrence after breast-conserving therapy. Better mammographic evaluation, better margin assessment, recognition of an extensive intraductal component and the use of adjuvant systemic therapy has improved the logo-regional control.

Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis.

PubMed

Hulit, J; Di Vizio, D; Pestell, R G

2001-01-01

Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors that regressed upon withdrawal of c-Myc expression. Almost one-half of the c-Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlating with tumor persistence on withdrawal of c-Myc transgene expression. These findings suggest maintenance of tumorigenesis may involve a second mutation within the Ras pathway.

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first

Breast cancer risk accumulation starts early – Prevention must also

PubMed Central

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

2014-01-01

Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

TAILORx finds no chemotherapy benefit for most early breast cancers

Cancer.gov

Findings from the TAILORx clinical trial show chemotherapy does not benefit most women with early breast cancer. The new data, released at the 2018 ASCO annual meeting, will help inform treatment decisions for many women with early-stage breast cancer.

Accelerated Partial Breast Irradiation Using Only Intraoperative Electron Radiation Therapy in Early Stage Breast Cancer

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

Maluta, Sergio; Dall'Oglio, Stefano, E-mail: stefano.dalloglio@ospedaleuniverona.it; Marciai, Nadia

2012-10-01

Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up ofmore » 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.« less

Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer.

PubMed

Smolarek, Amanda K; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S; Suh, Nanjoo

2012-11-01

Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P < 0.01) and 7.1 ± 0.7 g (P < 0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.

Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen-receptor positive, but not HER-2 breast cancer

PubMed Central

Smolarek, Amanda K.; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S.; Suh, Nanjoo

2012-01-01

Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ- or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). While administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (p<0.01) and 7.1 ± 0.7 g (p<0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (p<0.001) and 32% (p<0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of pro-apoptotic markers (BAX, cleaved-caspase 9, cleaved-caspase 3, cleaved-PARP) were increased, while anti-apoptotic markers (Bcl2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKC α), survival (PPARγ, PTEN, phospho-Akt) and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, appear to be promising agents for the prevention of hormone-dependent breast cancer. PMID:22964476

Risk of Breast Cancer among Young Women and Importance of Early Screening.

PubMed

Memon, Zahid Ali; Kanwal, Noureen; Sami, Munam; Larik, Parsa Azam; Farooq, Mohammad Zain

2015-01-01

Breast cancer is the most common type of cancer in women throughout the world. However, in comparison with Western women, it presents relatively early in women of Asian ethnicity. Early menarche, late menopause, use of OCP's, family history of benign or malignant breast disease, exposure to radiation and BMI in the under-weight range are well known risk factors for the development of breast cancer in premenopausal women. Early detection with the use of breast self-examination (BSE) and breast cancer screening programs can lead to a reduction in the mortality rates due to breast cancer. The aim of our study was to assess the risk factors for breast cancer among young women and to emphasize the importance of early screening among them. We conducted a cross-sectional study among women aged 18 to 25 using a self- administered questionnaire. Data was collected over a period of 6 months from June to December, 2014. A total of 300 young women selected randomly from Dow Medical College and various departments of Karachi University successfully completed the survey. Respondents were 18-25 years of age (mean age=21.5). Out of the 300 young females, 90 (30%) had at least one risk factor, 90 (30%) had two, 40 (13%) had three, 8 (2.7%) had four, 2 (0.7%) had five while one female was found to have six positive risk factors for breast cancer. Some 66 women (22%) experienced symptoms of breast cancer such as non-cyclical pain and lumps. While 222 women (74%) had never performed breast self-examination, 22 (7.3%) had had a breast examination done by a health professional while 32 (10.7%) had participated in breast screening programs. A total of 223 (74.3%) women considered breast cancer screening important for young women. The percentage of young women with risk factors for breast cancer was found to be alarmingly high. Therefore, screening for breast cancer should start at an early age especially in high risk groups. Awareness about breast self-examination should be emphasized

Cabbage compression early breast care on breast engorgement in primiparous women after cesarean birth: a controlled clinical trial

PubMed Central

Lim, A-Reum; Song, Ji-Ah; Hur, Myung-Haeng; Lee, Mi-Kyoung; Lee, Myeong Soo

2015-01-01

This study aimed to compare the effects of cabbage compression early breast care (CCEBC) and early breast care (EBC) on breast pain, breast hardness with general nursing breast care (GNBC) in primiparous women after cesarean birth. Sixty participants were divided to three groups including CCEBC, EBC and GNBC. Each group was treated with its intervention respectively more than 10 minutes before breast feeding from day two to day four after delivery. The primary outcomes were breast pain and breast hardness. Both CCEBC and EBC showed significantly lower pain level than GNBC at day 4 after delivery. There are significant differences of breast hardness among three groups. CCEBC group showed significantly lower breast hardness compared with EBC and GNBC. Neither core body temperature nor breast skin temperature was significantly different among the three groups. In conclusion, CCEBC may effective in relieving breast pain and breast hardness compared with EBC alone and GNBC in primiparous women after a cesarean birth. PMID:26885074

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

PubMed

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Minireview: Progesterone Regulation of Proliferation in the Normal Human Breast and in Breast Cancer: A Tale of Two Scenarios?

PubMed Central

Graham, J. Dinny; Clarke, Christine L.

2015-01-01

Progesterone (P), which signals through the P receptor (PR), is critical in normal development of the breast, but its signaling axis is also a major driver of breast cancer risk. Here we review recent advances in the understanding of P signaling in the normal human breast, with a focus on the importance of the balance between autocrine and paracrine signaling. To date, most data (which derive largely from mouse models or human breast cancer cell line studies) have demonstrated that the vast majority of PR+ cells appear to act as “sensor” cells, which respond to P stimulation by translating these hormonal cues into paracrine signals. However, growing evidence suggests that, dependent on the cellular context, P may also signal in an autocrine manner in a subset of cells in the normal mouse mammary gland and human breast. It has been suggested that it may be dysregulation of this autocrine signaling, resulting in a “switch” from a predominance of paracrine signaling to autocrine signaling in PR+ cells, which is an early event during breast tumorigenesis. This review summarizes current evidence in the literature that demonstrates the mechanisms through which P acts in the normal human breast, as well as highlighting the important questions that remain unanswered. PMID:26266959

Next generation sequencing applications for breast cancer research

PubMed Central

PETRIC, ROXANA COJOCNEANU; POP, LAURA-ANCUTA; JURJ, ANCUTA; RADULY, LAJOS; DUMITRASCU, DAN; DRAGOS, NICOLAE; NEAGOE, IOANA BERINDAN

2015-01-01

For some time, cancer has not been thought of as a disease, but as a multifaceted, heterogeneous complex of genotypic and phenotypic manifestations leading to tumorigenesis. Due to recent technological progress, the outcome of cancer patients can be greatly improved by introducing in clinical practice the advantages brought about by the development of next generation sequencing techniques. Biomedical suppliers have come up with various applications which medical researchers can use to characterize a patient’s disease from molecular and genetic point of view in order to provide caregivers with rapid and relevant information to guide them in choosing the most appropriate course of treatment, with maximum efficiency and minimal side effects. Breast cancer, whose incidence has risen dramatically, is a good candidate for these novel diagnosis and therapeutic approaches, particularly when referring to specific sequencing panels which are designed to detect germline or somatic mutations in genes that are involved in breast cancer tumorigenesis and progression. Benchtop next generation sequencing machines are becoming a more common presence in the clinical setting, empowering physicians to better treat their patients, by offering early diagnosis alternatives, targeted remedies, and bringing medicine a step closer to achieving its ultimate goal, personalized therapy. PMID:26609257

Early Breast Cancer Detection by Ultrawide Band Imaging with Dispersion Consideration

NASA Astrophysics Data System (ADS)

Xiao, Xia; Kikkawa, Takamaro

2008-04-01

Ultrawide band (UWB) microwave imaging is a promising method for early-stage breast cancer detection based on the large contrast of electric parameters between the tumor and the normal breast tissue. The tumor can be detected by analyzing the reflection and scattering behavior of the UWB microwave propagating in the breast. In this study, the tumor location is determined by comparing the waveforms resulted from the tumor-containing and tumor-free breasts. The frequency dispersive characteristics of the fatty breast tissue, skin and tumor are considered in the study to approach the actual electrical properties of the breast. The correct location and size are visualized for an early-stage tumor embedded in the breast using the principle of a confocal microwave imaging technique.

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice.

PubMed

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-02-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

Multiple Biomarker Panels for Early Detection of Breast Cancer in Peripheral Blood

PubMed Central

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers. PMID:24371830

Multiple biomarker panels for early detection of breast cancer in peripheral blood.

PubMed

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

Progesterone regulation of stem and progenitor cells in normal and malignant breast

PubMed Central

Axlund, Sunshine Daddario; Sartorius, Carol A.

2011-01-01

Progesterone plays an important, if not controversial, role in mammary epithelial cell proliferation and differentiation. Evidence supports that progesterone promotes rodent mammary carcinogenesis under some conditions, progesterone receptors (PR) are necessary for murine mammary gland tumorigenesis, and exogenous progestin use in post-menopausal women increases breast cancer risk. Thus, the progesterone/PR signaling axis can promote mammary tumorigenesis, albeit in a context dependent manner. A mechanistic basis for the tumor promoting actions of progesterone has thus far remained unknown. Recent studies, however, have identified a novel role for progesterone in controlling the number and function of stem and progenitor cell populations in the normal human and mouse mammary glands, and in human breast cancers. These discoveries promise to reshape our perception of progesterone function in the mammary gland, and have spawned new hypotheses for how progestins may increase the risk of breast cancer. Here we review studies on progesterone regulation of mammary stem cells in normal and malignant tissue, and their implications for breast cancer risk, tumorigenesis, and tumor behavior. PMID:21945473

Circular RNA hsa_circ_0001982 Promotes Breast Cancer Cell Carcinogenesis Through Decreasing miR-143.

PubMed

Tang, Yi-Yin; Zhao, Ping; Zou, Tian-Ning; Duan, Jia-Jun; Zhi, Rong; Yang, Si-Yuan; Yang, De-Chun; Wang, Xiao-Li

2017-11-01

Circular RNAs (circRNAs) are a type of noncoding RNAs generated from back-splicing, which have been verified to mediate multiple tumorigenesis. With the development of high-throughput sequencing, massive circRNAs are discovered in tumorous tissue. However, the potential physiological effect of circRNAs in breast cancer is still unknown. The purpose of this study is to investigate the expression profile of circRNA in breast cancer tissue and explore the in-depth regulatory mechanism in breast cancer tumorigenesis. In the present study, we screened the circRNA expression profiles in breast cancer tissue using circRNA microarray analysis. Totally 1705 circRNAs were identified to be significantly aberrant. Among these dysregulated circRNAs, hsa_circ_0001982 was markedly overexpressed in breast cancer tissue and cell lines. Bioinformatics analysis predicted that miR-143 acted as target of hsa_circ_0001982, which was confirmed by Dual-luciferase reporter assay. Loss-of-function and rescue experiments revealed that hsa_circ_0001982 knockdown suppressed breast cancer cell proliferation and invasion and induced apoptosis by targeting miR-143. In summary, our study preliminarily investigates the circRNA expression in breast cancer tissue and explores the role of competing endogenous RNA (ceRNA) mechanism in the progression, providing a novel insight for breast cancer tumorigenesis.

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

PubMed

Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

2017-06-01

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend <0.05 for all). The recall rate increased, while rate of screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend <0.05 for all). High compression pressure was associated with higher odds of interval breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

Exosomes in development, metastasis and drug resistance of breast cancer

PubMed Central

Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

2015-01-01

Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system. PMID:26052865

Reproduction and Breast Cancer Risk

PubMed Central

Hanf, Volker; Hanf, Dorothea

2014-01-01

Summary Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed. PMID:25759622

Aberrantly methylated DNA as a biomarker in breast cancer.

PubMed

Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

2013-01-01

Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis

PubMed Central

Chen, Wen-jun; Zhang, Xi; Wu, Cong-cong; Zhang, Chao-ying; Sun, Shuang-shuang; Wu, Jian

2017-01-01

Background There are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS. Results Radiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non-radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25. The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non-radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20. However, radiotherapy could not improve survival benefits, including overall survival, cancer-specific survival, breast-cancer-specific survival, and distant relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast events in older patients with DCIS. Materials and Methods PubMed and Embase database were searched for relevant studies. Hazard ratios (HRs), risk ratios (RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy in older patients. Conclusions Our study indicates that radiotherapy could slightly reduce the risk of local relapse in older patients with favorable early breast cancer. However, radiotherapy cannot translate into significant survival benefits. PMID:28415667

Early Detection and Screening for Breast Cancer.

PubMed

Coleman, Cathy

2017-05-01

To review the history, current status, and future trends related to breast cancer screening. Peer-reviewed articles, web sites, and textbooks. Breast cancer remains a complex, heterogeneous disease. Serial screening with mammography is the most effective method to detect early stage disease and decrease mortality. Although politics and economics may inhibit organized mammography screening programs in many countries, the judicious use of proficient clinical and self-breast examination can also identify small tumors leading to reduced morbidity. Oncology nurses have exciting opportunities to lead, facilitate, and advocate for delivery of high-quality screening services targeting individuals and communities. A practical approach is needed to translate the complexities and controversies surrounding breast cancer screening into improved care outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Apoptosis Pathway that is Defective in Early Breast Cancer

DTIC Science & Technology

2005-04-01

AD Award Number: DAMD17-02-1-0612 TITLE: A Novel Apoptosis Pathway that is Defective in Early Breast Cancer PRINCIPAL INVESTIGATOR: Scott Cramer...Defective in Early DAMD17-02-1-0612 Breast Cancer 6. AUTHOR(S) Scott Cramer, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...These experiments were intended to determine why breast cancer cells are resistant to this apoptosis pathway BODY. As outlined in the previous

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation

PubMed Central

Reddy, Jay P.; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M.; Donehower, Larry A.; Li, Yi

2010-01-01

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention. PMID:20133707

Denervation suppresses gastric tumorigenesis

PubMed Central

Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B.; Andersen, Gøran T.; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A.; Renz, Bernhard W.; Sandvik, Arne K.; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D.; Kaneko, Kazuhiro; Fox, James G.; Wang, Timothy C.; Chen, Duan

2015-01-01

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor–mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

PKCθ promotes c-Rel–driven mammary tumorigenesis in mice and humans by repressing estrogen receptor α synthesis

PubMed Central

Belguise, Karine; Sonenshein, Gail E.

2007-01-01

The vast majority of primary human breast cancer tissues display aberrant nuclear NF-κB c-Rel expression. A causal role for c-Rel in mammary tumorigenesis has been demonstrated using a c-Rel transgenic mouse model; however, tumors developed with a long latency, suggesting a second event is needed to trigger tumorigenesis. Here we show that c-Rel activity in the mammary gland is repressed by estrogen receptor α (ERα) signaling, and we identify an epigenetic mechanism in breast cancer mediated by activation of what we believe is a novel PKCθ-Akt pathway that leads to downregulation of ERα synthesis and derepression of c-Rel. ERα levels were lower in c-Rel–induced mammary tumors compared with normal mammary gland tissue. PKCθ induced c-Rel activity and target gene expression and promoted growth of c-Rel- and c-RelxCK2α–driven mouse mammary tumor–derived cell lines. RNA expression levels of PKCθ and c-Rel target genes were inversely correlated with ERα levels in human breast cancer specimens. PKCθ activated Akt, thereby inactivating forkhead box O protein 3a (FOXO3a) and leading to decreased synthesis of its target genes, ERα and p27Kip1. Thus we have shown that activation of PKCθ inhibits the FOXO3a/ERα/p27Kip1 axis that normally maintains an epithelial cell phenotype and induces c-Rel target genes, thereby promoting proliferation, survival, and more invasive breast cancer. PMID:18037997

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

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.

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

PubMed Central

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-01-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target. PMID:20093778

Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway

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

Karam, Manale; Legay, Christine; Auclair, Christian

2012-03-10

Protein kinase D1, PKD1, is a novel serine/threonine kinase whose altered expression and dysregulation in many tumors as well as its activation by several mitogens suggest that this protein could regulate proliferation and tumorigenesis. Nevertheless, the precise signaling pathways used are still unclear and the potential direct role of PKD1 in tumor development and progression has not been yet investigated. In order to clarify the role of PKD1 in cell proliferation and tumorigenesis, we studied the effects of PKD1 overexpression in a human adenocarcinoma breast cancer cell line, MCF-7 cells. We demonstrated that overexpression of PKD1 specifically promotes MCF-7 cellmore » proliferation through accelerating G0/G1 to S phase transition of the cell cycle. Moreover, inhibition of endogenous PKD1 significantly reduced cell proliferation. Taken together, these results clearly strengthen the regulatory role of PKD1 in cell growth. We also demonstrated that overexpression of PKD1 specifically diminished serum- and anchorage-dependence for proliferation and survival in vitro and allowed MCF-7 cells to form tumors in vivo. Thus, all these data highlight the central role of PKD1 in biological processes which are hallmarks of malignant transformation. Analysis of two major signaling pathways implicated in MCF-7 cell proliferation showed that PKD1 overexpression significantly increased ERK1/2 phosphorylation state without affecting Akt phosphorylation. Moreover, PKD1 overexpression-stimulated cell proliferation and anchorage-independent growth were totally impaired by inhibition of the MEK/ERK kinase cascade. However, neither of these effects was affected by blocking the PI 3-kinase/Akt signaling pathway. Thus, the MEK/ERK signaling appears to be a determining pathway mediating the biological effects of PKD1 in MCF-7 cells. Taken together, all these data demonstrate that PKD1 overexpression increases the aggressiveness of MCF-7 breast cancer cells through enhancing their

Biopsy Findings After Breast Conservation Therapy for Early-Stage Invasive Breast Cancer

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

Vapiwala, Neha; Starzyk, Jill; Harris, Eleanor E.

2007-10-01

Purpose: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. Methods and Materials: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. Results: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median timemore » to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if {>=}51 years, 57% if 36-50 years, and 83% if {<=}35 years (p = 0.05). The PBR correlated directly with the interval after radiotherapy: 49% if {<=}60 months, 59% if 60.1-120 months, 77% if 120.1-180 months, and 100% if >180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p {>=} 0.15). Conclusion: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.« less

Nipple Discharge: An Early Warning Sign of Breast Cancer

PubMed Central

Parthasarathy, Veda; Rathnam, Usharani

2012-01-01

Nipple discharge (ND) can be the earliest presenting symptom of breast cancer. We hereby present two cases of breast cancer with no palpable mass manifesting as isolated ND, which was whitish in color. In both cases, cytology of the discharge revealed highly pleomorphic cells indicating a high grade malignancy. Mammography showed diffuse, extensive microcalcifications. Simple mastectomy with axillary clearance was done. Histology in both cases revealed diffusely spreading intraductal carcinoma, with focus of microinvasion in one case. ND if scanty or not blood stained is often ignored by the patients and at times, the clinicians. This article highlights that ND can be an early warning sign of intraductal carcinomas that are non-invasive in early stage. Irrespective of the color or nature of the discharge, unilateral ND needs to be evaluated. Proper clinical assessment, cytological evaluation of the ND, and mammography ought to be performed in all such cases. Considering the low level of awareness in women regarding the warning signs of breast cancer, the current focus is to create “breast awareness.” Women should be sensitized to recognize any unusual changes in their breasts and report to their health care providers at the earliest. PMID:23189234

Differences in clinician understanding and management of early menopause after breast cancer.

PubMed

Sayakhot, P; Teede, H J; Gibson-Helm, M; Vincent, A

2013-08-01

Investigation of clinicians' understanding of early menopause diagnosis/management in women with breast cancer. A cross-sectional study of 176 randomly recruited Australian clinicians (35 gynecologists, 35 endocrinologists, 36 oncologists, 35 breast surgeons and 35 general practitioners (GPs)) involved in the care of women with breast cancer. This questionnaire study utilized an index case to assess understanding of early menopause diagnosis and management. Analysis involved descriptive statistics, χ² tests and Student's t-test. Significant differences between clinician groups regarding diagnostic criteria for early menopause were observed; gynecologists, endocrinologists and GPs selected amenorrhea > 12 months, whereas oncologists and breast surgeons selected elevated serum follicle stimulating hormone level (p < 0.05). Non-hormonal treatment was preferred by most clinician groups. Complementary/alternative medicines were more commonly prescribed by breast surgeons (57%), gynecologists (54%) and endocrinologists (49%) compared to oncologists (28%) or GPs (9%) (p = 0.0001). Exercise (63%) and nutrition (66%) were selected by most gynecologists for treatment of hot flushes, whereas endocrinologists (91%), oncologists (94%), breast surgeons (69%) and GPs (63%) prescribed venlafaxine. Hormone therapy was mainly prescribed by breast surgeons (43%) compared to other groups (p = 0.001). Most clinicians reported that the main problem with menopausal therapies was failure to resolve hot flushes. Exercise, lifestyle and stress management were recommended by all clinician groups for treatment of anxiety/depression. This exploratory study demonstrated a lack of consensus between clinician groups in their investigation, diagnosis and management of early menopause in women with breast cancer, with implications for both diagnosis and treatment.

Exosomes in development, metastasis and drug resistance of breast cancer.

PubMed

Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

2015-08-01

Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

High-fat diet enhances mammary tumorigenesis and pulmonary metastasis and alters inflammatory and angiogenic profiles in MMTV-PyMT mice

USDA-ARS?s Scientific Manuscript database

The MMTV-PyMT transgenic mouse model is commonly used to study luminal B breast cancer, which has a lower prevalence but a worse prognosis. The objective of the present study was to determine whether an obesogenic, high-fat diet enhances primary tumorigenesis and pulmonary metastasis in female MMTV...

An early history of human breast cancer: West meets East.

PubMed

Yan, Shou-He

2013-09-01

Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

Breast-feeding Duration: Early Weaning-Do We Sufficiently Consider the Risk Factors?

PubMed

Karall, Daniela; Ndayisaba, Jean-Pierre; Heichlinger, Angelika; Kiechl-Kohlendorfer, Ursula; Stojakovic, Sarah; Leitner, Hermann; Scholl-Bürgi, Sabine

2015-11-01

Breast-feeding is the recommended form of nutrition for the first 6 months. This target is unmet, however, in most industrialized regions. We evaluated aspects of breast-feeding in a cohort of mother-baby dyads. Breast-feeding practices in 555 mother-baby dyads were prospectively studied for 24 months (personal interview at birth and 7 structured telephone interviews). Of the babies, 71.3% were fully breast-fed on discharge from maternity hospitals and 11.9% were partially breast-feed. Median breast-feeding duration was 6.93 (interquartile range 2.57-11.00) months; for full (exclusive) breast-feeding 5.62 (interquartile range 3.12-7.77) months; 61.7% received supplemental feedings during the first days of life. Breast-feeding duration in babies receiving supplemental feedings was significantly shorter (median 5.06 months versus 8.21 months, P < 0.001). At 6 months, 9.4% of the mothers were exclusively and 39.5% partially breast-feeding. Risk factors for early weaning were early supplemental feedings (odds ratio [OR] 2.87, 95% CI 1.65-4.98), perceived milk insufficiency (OR 7.35, 95% CI 3.59-15.07), low breast-feeding self-efficacy (a mother's self-confidence in her ability to adequately feed her baby) (OR 3.42, 95% CI 1.48-7.94), lower maternal age (OR 3.89, 95% CI 1.45-10.46), and lower education level of the mother (OR 7.30, 95% CI 2.93-18.20). The recommended full breast-feeding duration of the first 6 months of life was not reached. Sociodemographic variables and factors directly related to breast-feeding practices play an important role on breast-feeding duration/weaning in our region. Understanding risk factors will provide insights to give better support to mothers and prevent short- and long-term morbidity following early weaning.

UWB based low-cost and non-invasive practical breast cancer early detection

NASA Astrophysics Data System (ADS)

Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

2017-03-01

Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

Breast Camps for Awareness and Early Diagnosis of Breast Cancer in Countries With Limited Resources: A Multidisciplinary Model From Kenya.

PubMed

Sayed, Shahin; Moloo, Zahir; Ngugi, Anthony; Allidina, Amyn; Ndumia, Rose; Mutuiri, Anderson; Wasike, Ronald; Wahome, Charles; Abdihakin, Mohamed; Kasmani, Riaz; Spears, Carol D; Oigara, Raymond; Mwachiro, Elizabeth B; Busarla, Satya V P; Kibor, Kibet; Ahmed, Abdulaziz; Wawire, Jonathan; Sherman, Omar; Saleh, Mansoor; Zujewski, Jo Anne; Dawsey, Sanford M

2016-09-01

Breast cancer is the most common cancer of women in Kenya. There are no national breast cancer early diagnosis programs in Kenya. The objective was to conduct a pilot breast cancer awareness and diagnosis program at three different types of facilities in Kenya. This program was conducted at a not-for-profit private hospital, a faith-based public hospital, and a government public referral hospital. Women aged 15 years and older were invited. Demographic, risk factor, knowledge, attitudes, and screening practice data were collected. Breast health information was delivered, and clinical breast examinations (CBEs) were performed. When appropriate, ultrasound imaging, fine-needle aspirate (FNA) diagnoses, core biopsies, and onward referrals were provided. A total of 1,094 women were enrolled in the three breast camps. Of those, 56% knew the symptoms and signs of breast cancer, 44% knew how breast cancer was diagnosed, 37% performed regular breast self-exams, and 7% had a mammogram or breast ultrasound in the past year. Of the 1,094 women enrolled, 246 (23%) had previously noticed a lump in their breast. A total of 157 participants (14%) had abnormal CBEs, of whom 111 had ultrasound exams, 65 had FNAs, and 18 had core biopsies. A total of 14 invasive breast cancers and 1 malignant phyllodes tumor were diagnosed Conducting a multidisciplinary breast camp awareness and early diagnosis program is feasible in different types of health facilities within a low- and middle-income country setting. This can be a model for breast cancer awareness and point-of-care diagnosis in countries with limited resources like Kenya. This work describes a novel breast cancer awareness and early diagnosis demonstration program in a low- and middle-income country within a limited resource setting. The program includes breast self-awareness and breast cancer education, clinical exams, and point-of-care diagnostics for women in three different types of health facilities in Kenya. This pilot

Potential of Breastmilk Analysis to Inform Early Events in Breast Carcinogenesis: Rationale and Considerations

PubMed Central

Murphy, Jeanne; Sherman, Mark E.; Browne, Eva P.; Caballero, Ana I.; Punska, Elizabeth C.; Pfeiffer, Ruth M.; Yang, Hannah P.; Lee, Maxwell; Yang, Howard; Gierach, Gretchen L.; Arcaro, Kathleen F.

2016-01-01

This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g. hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer. PMID:27107568

Breast Camps for Awareness and Early Diagnosis of Breast Cancer in Countries With Limited Resources: A Multidisciplinary Model From Kenya

PubMed Central

Moloo, Zahir; Ngugi, Anthony; Allidina, Amyn; Ndumia, Rose; Mutuiri, Anderson; Wasike, Ronald; Wahome, Charles; Abdihakin, Mohamed; Kasmani, Riaz; Spears, Carol D.; Oigara, Raymond; Mwachiro, Elizabeth B.; Busarla, Satya V.P.; Kibor, Kibet; Ahmed, Abdulaziz; Wawire, Jonathan; Sherman, Omar; Saleh, Mansoor; Zujewski, Jo Anne; Dawsey, Sanford M.

2016-01-01

Background. Breast cancer is the most common cancer of women in Kenya. There are no national breast cancer early diagnosis programs in Kenya. Objective. The objective was to conduct a pilot breast cancer awareness and diagnosis program at three different types of facilities in Kenya. Methods. This program was conducted at a not-for-profit private hospital, a faith-based public hospital, and a government public referral hospital. Women aged 15 years and older were invited. Demographic, risk factor, knowledge, attitudes, and screening practice data were collected. Breast health information was delivered, and clinical breast examinations (CBEs) were performed. When appropriate, ultrasound imaging, fine-needle aspirate (FNA) diagnoses, core biopsies, and onward referrals were provided. Results. A total of 1,094 women were enrolled in the three breast camps. Of those, 56% knew the symptoms and signs of breast cancer, 44% knew how breast cancer was diagnosed, 37% performed regular breast self-exams, and 7% had a mammogram or breast ultrasound in the past year. Of the 1,094 women enrolled, 246 (23%) had previously noticed a lump in their breast. A total of 157 participants (14%) had abnormal CBEs, of whom 111 had ultrasound exams, 65 had FNAs, and 18 had core biopsies. A total of 14 invasive breast cancers and 1 malignant phyllodes tumor were diagnosed Conclusion. Conducting a multidisciplinary breast camp awareness and early diagnosis program is feasible in different types of health facilities within a low- and middle-income country setting. This can be a model for breast cancer awareness and point-of-care diagnosis in countries with limited resources like Kenya. Implications for Practice: This work describes a novel breast cancer awareness and early diagnosis demonstration program in a low- and middle-income country within a limited resource setting. The program includes breast self-awareness and breast cancer education, clinical exams, and point-of-care diagnostics for

Elevated NIBP/TRAPPC9 mediates tumorigenesis of cancer cells through NFκB signaling

PubMed Central

Wang, Hong; Yang, Wensheng; Li, Fang; Yang, Fan; Yu, Daohai; Ramsey, Frederick V.; Tuszyski, George P.; Hu, Wenhui

2015-01-01

Regulatory mechanisms underlying constitutive and inducible NFκB activation in cancer remain largely unknown. Here we investigated whether a novel NIK- and IKK2-binding protein (NIBP) is required for maintaining malignancy of cancer cells in an NFκB-dependent manner. Real-time polymerase chain reaction analysis of a human cancer survey tissue-scan cDNA array, immunostaining of a human frozen tumor tissue array and immunoblotting of a high-density reverse-phase cancer protein lysate array showed that NIBP is extensively expressed in most tumor tissues, particularly in breast and colon cancer. Lentivirus-mediated NIBP shRNA knockdown significantly inhibited the growth/proliferation, invasion/migration, colony formation and xenograft tumorigenesis of breast (MDA-MB-231) or colon (HCT116) cancer cells. NIBP overexpression in HCT116 cells promoted cell proliferation, migration and colony formation. Mechanistically, NIBP knockdown in cancer cells inhibited cytokine-induced activation of NFκB luciferase reporter, thus sensitizing the cells to TNFα-induced apoptosis. Endogenous NIBP bound specifically to the phosphorylated IKK2 in a TNFα-dependent manner. NIBP knockdown transiently attenuated TNFα-stimulated phosphorylation of IKK2/p65 and degradation of IκBα. In contrast, NIBP overexpression enhanced TNFα-induced NFκB activation, thus inhibiting constitutive and TNFα-induced apoptosis. Collectively, our data identified important roles of NIBP in promoting tumorigenesis via NFκΒ signaling, spotlighting NIBP as a promising target in cancer therapeutic intervention. PMID:25704885

A Genetic Interaction Screen for Breast Cancer Progression Driver Genes

DTIC Science & Technology

2013-06-01

analysis of genetic alterations in human breast cancers has revealed that individual tumors accumulate mutations in approximately ninety different genes ...cancer. We performed a screen to test the roles of seventy breast cancer mutated genes in mouse mammary tumorigenesis using the MMTV-PyVT mouse breast...cancer model and piggyBac insertional mutation strains. We found that insertional mutations in 23 genes altered the onset of tumor formation and four

Genetically engineered mice as experimental tools to dissect the critical events in breast cancer.

PubMed

Menezes, Mitchell E; Das, Swadesh K; Emdad, Luni; Windle, Jolene J; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2014-01-01

Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited from breakthrough advances in both genetically engineered mouse (GEM) models and xenograft transplantation technologies. The vast array of breast cancer mouse models currently available is testimony to the complexity of mammary tumorigenesis and attempts by investigators to accurately portray the heterogeneity and intricacies of this disease. Distinct molecular changes that drive various aspects of tumorigenesis, such as alterations in tumor cell proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug resistance have been evaluated using the currently available GEM breast cancer models. GEM breast cancer models are also being exploited to evaluate and validate the efficacy of novel therapeutics, vaccines, and imaging modalities for potential use in the clinic. This review provides a synopsis of the various GEM models that are expanding our knowledge of the nuances of breast cancer development and progression and can be instrumental in the development of novel prevention and therapeutic approaches for this disease. © 2014 Elsevier Inc. All rights reserved.

Genetically Engineered Mice as Experimental Tools to Dissect the Critical Events in Breast Cancer

PubMed Central

Menezes, Mitchell E.; Das, Swadesh K.; Emdad, Luni; Windle, Jolene J.; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited from breakthrough advances in both genetically engineered mouse (GEM) models and xenograft transplantation technologies. The vast array of breast cancer mouse models currently available is testimony to the complexity of mammary tumorigenesis and attempts by investigators to accurately portray the heterogeneity and intricacies of this disease. Distinct molecular changes that drive various aspects of tumorigenesis, such as alterations in tumor cell proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug resistance have been evaluated using the currently available GEM breast cancer models. GEM breast cancer models are also being exploited to evaluate and validate the efficacy of novel therapeutics, vaccines, and imaging modalities for potential use in the clinic. This review provides a synopsis of the various GEM models that are expanding our knowledge of the nuances of breast cancer development and progression and can be instrumental in the development of novel prevention and therapeutic approaches for this disease. PMID:24889535

Breast cancer early detection via tracking of skin back-scattered secondary speckle patterns

NASA Astrophysics Data System (ADS)

Bennett, Aviya; Sirkis, Talia; Beiderman, Yevgeny; Agdarov, Sergey; Beiderman, Yafim; Zalevsky, Zeev

2018-02-01

Breast cancer has become a major cause of death among women. The lifetime risk of a woman developing this disease has been established as one in eight. The most useful way to reduce breast cancer death is to treat the disease as early as possible. The existing methods of early diagnostics of breast cancer are mainly based on screening mammography or Magnetic Resonance Imaging (MRI) periodically conducted at medical facilities. In this paper the authors proposing a new approach for simple breast cancer detection. It is based on skin stimulation by sound waves, illuminating it by laser beam and tracking the reflected secondary speckle patterns. As first approach, plastic balls of different sizes were placed under the skin of chicken breast and detected by the proposed method.

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress.

PubMed

McCormick, Beryl

2012-09-01

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.

Oncogene-Induced Changes in Mammary Cell Fate and EMT in Breast Tumorigenesis

DTIC Science & Technology

2015-04-01

have worked on the project? Name: Lauren Walheim Project Role: Chemistry pre-medicine undergraduate student Researcher Identifier (e.g. ORCID ID...Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an...Examine if IGF1R alters mammary cell fate in vivo and the effect this has on mammary tumorigenesis (months 13-30) ...…………………………………………….......11 2a

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

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation.

PubMed

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B; Bass, Barbara L; Miltenburg, Darlene M; Butler, E Brian; Teh, Bin S

2015-12-01

Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate (192)Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes.

The roles of PIKE in tumorigenesis

PubMed Central

Qi, Qi; Ye, Keqiang

2013-01-01

Tumorigenesis is the process by which normal cells evolve the capacity to evade and overcome the constraints usually placed upon their growth and survival. To ensure the integrity of organs and tissues, the balance of cell proliferation and cell death is tightly maintained. The proteins controlling this balance are either considered oncogenes, which promote tumorigenesis, or tumor suppressors, which prevent tumorigenesis. Phosphoinositide 3-kinase enhancer (PIKE) is a family of GTP-binding proteins that possess anti-apoptotic functions and play an important role in the central nervous system. Notably, accumulating evidence suggests that PIKE is a proto-oncogene involved in tumor progression. The PIKE gene (CENTG1) is amplified in a variety of human cancers, leading to the resistance against apoptosis and the enhancement of invasion. In this review, we will summarize the functions of PIKE proteins in tumorigenesis and discuss their potential implications in cancer therapy. PMID:23770988

Early retirement and non-employment after breast cancer.

PubMed

Lindbohm, M-L; Kuosma, E; Taskila, T; Hietanen, P; Carlsen, K; Gudbergsson, S; Gunnarsdottir, H

2014-06-01

This study examined whether workplace support, sociodemographic factors and co-morbidity are associated with early retirement or non-employment due to other reasons among breast cancer survivors. We also compared quality of life and chronic symptoms (pain, fatigue, anxiety and depression) among employed, retired and other non-employed breast cancer survivors. We identified breast cancer survivors diagnosed between 1997 and 2002 from either a hospital or a cancer registry in Denmark, Finland, Iceland and Norway (NOCWO study). All patients had been treated with curative intent. Information on employment, co-morbidity and support was collected via a questionnaire. The sample included 1111 working-aged cancer-free survivors who had been employed at the time of diagnosis. We used multinomial logistic regression models to analyse the association of various determinants with early retirement and other non-employment (due to unemployment, subsidized employment or being a homemaker). Low education, low physical quality of life, co-morbidity and pain were associated with both early retirement and other non-employment after cancer. Other non-employed survivors also rated their mental quality of life as lower and experienced anxiety and fatigue more often than all the other survivors. Moreover, they reported a lower level of supervisor support after their diagnosis than the employed survivors. Retired survivors more often reported weak support from colleagues. Differences in ill health and functional status between various groups of non-employed cancer survivors need to be considered when planning policy measures for improving the labour market participation of this population and preventing their early withdrawal from working life. Copyright © 2013 John Wiley & Sons, Ltd.

Activation of HERV-K Env protein is essential for tumorigenesis and metastasis of breast cancer cells

PubMed Central

Lin, Kevin; Lu, Yue; Shen, Jianjun; Johanning, Gary L.; Wang-Johanning, Feng

2016-01-01

Human endogenous retrovirus type K (HERV-K) Env protein was previously demonstrated to be overexpressed in human breast cancer (BC) cells and tissues. However, the molecular pathways driving the specific alterations are unknown. We now show that knockdown of its expression with an shRNA (shRNAenv) blocked BC cell proliferation, migration, and invasion. shRNAenv transduction also attenuated the ability of BC cells to form tumors, and notably prevented metastasis. Mechanistically, downregulation of HERV-K blocked expression of tumor-associated genes that included Ras, p-RSK, and p-ERK. The major upstream regulators influenced by HERV-K knockdown were p53, TGF- β1, and MYC. Of interest, when the HERV-K env gene was overexpressed in shRNAenv-transduced BC cells using an HERV-K env expression vector, Ras/Raf/MEK/ERK pathway signaling was restored. CDK5, which alters p53 phosphorylation in some cancers, was upregulated and p53 was downregulated when HERV-K was overexpressed. CDK5 is also a mediator of TGF-β1-induced epithelial-mesenchymal transition and migration in cancer cells, and is involved in tumor formation. Importantly, reductions in migration, invasion, and transformation of BC cells stably transduced with shRNAenv was reversed after adding back a vector with a synonymous mutation of HERV-K env. Taken together, these results indicate that HERV-K Env protein plays an important role in tumorigenesis and metastasis of BC. PMID:27557521

Big data analytics for early detection of breast cancer based on machine learning

NASA Astrophysics Data System (ADS)

Ivanova, Desislava

2017-12-01

This paper presents the concept and the modern advances in personalized medicine that rely on technology and review the existing tools for early detection of breast cancer. The breast cancer types and distribution worldwide is discussed. It is spent time to explain the importance of identifying the normality and to specify the main classes in breast cancer, benign or malignant. The main purpose of the paper is to propose a conceptual model for early detection of breast cancer based on machine learning for processing and analysis of medical big dataand further knowledge discovery for personalized treatment. The proposed conceptual model is realized by using Naive Bayes classifier. The software is written in python programming language and for the experiments the Wisconsin breast cancer database is used. Finally, the experimental results are presented and discussed.

Red-breasted nuthatches detect early increases in spruce budworm populations

Treesearch

Hewlette S. Crawford; Daniel T. Jennings; Timothy L. Stone

1990-01-01

Early suppression .of increasing spruce budworm populations is essential to prevent epidemics; however, early changes in budworm numbers are difficult to detect. An effective and inexpensive method to detect early increases is needed. Red-breasted nuthatches eat more spruce budworm larvae and pupae as the insect increases in number. We estimated the number of large...

Chest wall leiomyosarcoma after breast-conservative therapy for early-stage breast cancer in a young woman with Li-Fraumeni syndrome.

PubMed

Henry, Eve; Villalobos, Victor; Million, Lynn; Jensen, Kristin C; West, Robert; Ganjoo, Kristen; Lebensohn, Alexandra; Ford, James M; Telli, Melinda L

2012-08-01

Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

Recursive SVM biomarker selection for early detection of breast cancer in peripheral blood.

PubMed

Zhang, Fan; Kaufman, Howard L; Deng, Youping; Drabier, Renee

2013-01-01

Breast cancer is worldwide the second most common type of cancer after lung cancer. Traditional mammography and Tissue Microarray has been studied for early cancer detection and cancer prediction. However, there is a need for more reliable diagnostic tools for early detection of breast cancer. This can be a challenge due to a number of factors and logistics. First, obtaining tissue biopsies can be difficult. Second, mammography may not detect small tumors, and is often unsatisfactory for younger women who typically have dense breast tissue. Lastly, breast cancer is not a single homogeneous disease but consists of multiple disease states, each arising from a distinct molecular mechanism and having a distinct clinical progression path which makes the disease difficult to detect and predict in early stages. In the paper, we present a Support Vector Machine based on Recursive Feature Elimination and Cross Validation (SVM-RFE-CV) algorithm for early detection of breast cancer in peripheral blood and show how to use SVM-RFE-CV to model the classification and prediction problem of early detection of breast cancer in peripheral blood.The training set which consists of 32 health and 33 cancer samples and the testing set consisting of 31 health and 34 cancer samples were randomly separated from a dataset of peripheral blood of breast cancer that is downloaded from Gene Express Omnibus. First, we identified the 42 differentially expressed biomarkers between "normal" and "cancer". Then, with the SVM-RFE-CV we extracted 15 biomarkers that yield zero cross validation score. Lastly, we compared the classification and prediction performance of SVM-RFE-CV with that of SVM and SVM Recursive Feature Elimination (SVM-RFE). We found that 1) the SVM-RFE-CV is suitable for analyzing noisy high-throughput microarray data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance (Area Under

miR-100 Induces Epithelial-Mesenchymal Transition but Suppresses Tumorigenesis, Migration and Invasion

PubMed Central

Chen, Dahu; Sun, Yutong; Yuan, Yuan; Han, Zhenbo; Zhang, Peijing; Zhang, Jinsong; You, M. James; Teruya-Feldstein, Julie; Wang, Min; Gupta, Sumeet; Hung, Mien-Chie; Liang, Han; Ma, Li

2014-01-01

Whether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion. PMID:24586203

Sasa health exerts a protective effect on Her2/NeuN mammary tumorigenesis.

PubMed

Ren, Mingqiang; Reilly, R Todd; Sacchi, Nicoletta

2004-01-01

Bamboo grass leaves of different Sasa species have been widely used in food and medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa Health. This extract was reported to inhibit both the development and growth of mammary tumors in a mammary tumor strain of virgin SHN mice (1). We found that Sasa Health exerts a significant protective effect on spontaneous mammary tumorigenesis in another mouse model of human breast cancer, the transgenic FVB-Her2/NeuN mouse model. Two cohorts of Her2/NeuN female mice of different age (eleven-week-old and twenty-four-week-old) chronically treated with Sasa Health in drinking water showed both a delay in the development of tumors and reduced tumor multiplicity. Sasa Health also induced inhibition of mammary duct branching and side bud development in association with reduced angiogenesis. Altogether these findings indicate that Sasa Health contains phytochemicals that can effectively retard spontaneous mammary tumorigenesis.

Novel Multistatic Adaptive Microwave Imaging Methods for Early Breast Cancer Detection

NASA Astrophysics Data System (ADS)

Xie, Yao; Guo, Bin; Li, Jian; Stoica, Petre

2006-12-01

Multistatic adaptive microwave imaging (MAMI) methods are presented and compared for early breast cancer detection. Due to the significant contrast between the dielectric properties of normal and malignant breast tissues, developing microwave imaging techniques for early breast cancer detection has attracted much interest lately. MAMI is one of the microwave imaging modalities and employs multiple antennas that take turns to transmit ultra-wideband (UWB) pulses while all antennas are used to receive the reflected signals. MAMI can be considered as a special case of the multi-input multi-output (MIMO) radar with the multiple transmitted waveforms being either UWB pulses or zeros. Since the UWB pulses transmitted by different antennas are displaced in time, the multiple transmitted waveforms are orthogonal to each other. The challenge to microwave imaging is to improve resolution and suppress strong interferences caused by the breast skin, nipple, and so forth. The MAMI methods we investigate herein utilize the data-adaptive robust Capon beamformer (RCB) to achieve high resolution and interference suppression. We will demonstrate the effectiveness of our proposed methods for breast cancer detection via numerical examples with data simulated using the finite-difference time-domain method based on a 3D realistic breast model.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PubMed

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer.

PubMed

Gasparri, Maria Luisa; Casorelli, Assunta; Bardhi, Erlisa; Besharat, Aris Raad; Savone, Delia; Ruscito, Ilary; Farooqi, Ammad Ahmad; Papadia, Andrea; Mueller, Michael David; Ferretti, Elisabetta; Benedetti Panici, Pierluigi

2017-05-01

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

Early, regular breast-milk pumping may lead to early breast-milk feeding cessation.

PubMed

Yourkavitch, Jennifer; Rasmussen, Kathleen M; Pence, Brian W; Aiello, Allison; Ennett, Susan; Bengtson, Angela M; Chetwynd, Ellen; Robinson, Whitney

2018-06-01

To estimate the effect of early, regular breast-milk pumping on time to breast-milk feeding (BMF) and exclusive BMF cessation, for working and non-working women. Using the Infant Feeding Practices Survey II (IFPS II), we estimated weighted hazard ratios (HR) for the effect of regular pumping (participant defined) compared with non-regular/not pumping, reported at month 2, on both time to BMF cessation (to 12 months) and time to exclusive BMF cessation (to 6 months), using inverse probability weights to control confounding. USA, 2005-2007. BMF (n 1624) and exclusively BMF (n 971) IFPS II participants at month 2. The weighted HR for time to BMF cessation was 1·62 (95 % CI 1·47, 1·78) and for time to exclusive BMF cessation was 1·14 (95 % CI 1·03, 1·25). Among non-working women, the weighted HR for time to BMF cessation was 2·05 (95 % CI 1·84, 2·28) and for time to exclusive BMF cessation was 1·10 (95 % CI 0·98, 1·22). Among working women, the weighted HR for time to BMF cessation was 0·90 (95 % CI 0·75, 1·07) and for time to exclusive BMF cessation was 1·14 (95 % CI 0·96, 1·36). Overall, regular pumpers were more likely to stop BMF and exclusive BMF than non-regular/non-pumpers. Non-working regular pumpers were more likely than non-regular/non-pumpers to stop BMF. There was no effect among working women. Early, regular pumpers may need specialized support to maintain BMF.

Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats.

PubMed

Sriwiriyajan, Somchai; Tedasen, Aman; Lailerd, Narissara; Boonyaphiphat, Pleumjit; Nitiruangjarat, Anupong; Deng, Yan; Graidist, Potchanapond

2016-01-01

Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P. nigrum extract (PFPE) against breast cancer cells and N-nitrosomethylurea (NMU)-induced mammary tumorigenesis in rats. The cytotoxic effects and the mechanism of action were investigated in breast cancer cells using the MTT assay and Western blot analysis, respectively. An acute toxicity study was conducted according to the Organization for Economic Co-operation and Development guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anticancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basal-like ones by induction of apoptosis. In addition, PFPE exhibited greater selectivity against breast cancer cells than colorectal cancer, lung cancer, and neuroblastoma cells. In an acute toxicity study, a single oral administration of PFPE at a dose of 5,000 mg/kg body weight resulted in no mortality and morbidity during a 14-day observation period. For the cancer preventive study, the incidence of tumor-bearing rats was 10% to 20% in rats treated with PFPE. For the anticancer activity study, the growth rate of tumors in the presence of PFPE-treated groups was much slower when compared with the control and vehicle groups. The extract itself caused no changes to the biochemical and hematologic parameters when compared with the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent antitumor effect on mammary tumorigenesis in rats. ©2015 American Association for Cancer Research.

Early microbial contact, the breast milk microbiome and child health.

PubMed

Rautava, S

2016-02-01

The significance of contact with microbes in early life for subsequent health has been the subject of intense research during the last 2 decades. Disturbances in the establishment of the indigenous intestinal microbiome caused by cesarean section delivery or antibiotic exposure in early life have been linked to the risk of immune-mediated and inflammatory conditions such as atopic disorders, inflammatory bowel disease and obesity later in life. Distinct microbial populations have recently been discovered at maternal sites including the amniotic cavity and breast milk, as well as meconium, which have previously been thought to be sterile. Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary. Breast milk is known to modulate immune and metabolic programming. The breast milk microbiome is hypothesized to guide infant gut colonization and is affected by maternal health status and mode of delivery. Immunomodulatory factors in breast milk interact with the maternal and infant gut microbiome and may mediate some of the health benefits associated with breastfeeding. The intimate connection between the mother and the fetus or the infant is a potential target for microbial therapeutic interventions aiming to support healthy microbial contact and protect against disease.

MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.

PubMed

Nassar, Farah J; Nasr, Rihab; Talhouk, Rabih

2017-04-01

Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results. Copyright © 2016 Elsevier Inc. All rights reserved.

Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

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

Shi, Yongguo, E-mail: 1138303166@qq.com; Lu, Jianwei, E-mail: jianwei2010077@163.com; Zhou, Jing, E-mail: 2310848@163.com

2014-04-04

Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question,more » we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.« less

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation

PubMed Central

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B.; Bass, Barbara L.; Miltenburg, Darlene M.; Butler, E. Brian

2015-01-01

Purpose Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. Material and methods We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate 192Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. Results After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Conclusions Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. PMID:26816499

Partial breast irradiation for early breast cancer.

PubMed

Hickey, Brigid E; Lehman, Margot; Francis, Daniel P; See, Adrienne M

2016-07-18

Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. We included

The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

PubMed Central

Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

2016-01-01

Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways. PMID:26784169

The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis.

PubMed

Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

2016-01-14

Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

Effectiveness of early detection on breast cancer mortality reduction in Catalonia (Spain)

PubMed Central

2009-01-01

Background At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ). Methods We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG. Results Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years. Conclusion In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain). PMID:19754959

Breast-conserving therapy for early-stage breast cancer in Chinese women: a meta-analysis of case-control studies.

PubMed

Cai, Xiaopeng; Liu, Xu; Yu, Haitao; Li, Jiguang; Zheng, Xinyu

2012-01-01

Breast cancer has a high incidence worldwide, while Chinese patients have some special characteristics compared to Western patients. A meta-analysis was carried out to determine the effectiveness of breast-conserving therapy (BCT) or mastectomy therapy (MT) for early-stage breast cancers in Chinese women. A fully recursive literature search was conducted in the Chinese Biomedical Literature Database. Case-control trials were considered for inclusion. Analyses were carried out using the Review Manager software (RevMan, version 5.0). The meta-analysis showed that the 3-year or 5-year overall survival, the locoregional recurrence rate, and the metastasis rate were not statistically different between the BCT group and the MT group, but the complication recurrence rate increased in the MT group. Subgroup analysis indicated that no significant differences were observed in the affected limb swelling recurrence rate between the BCT group and the MT group. BCT was the better choice than MT for Chinese women with early-stage breast cancer. Copyright © 2012 S. Karger AG, Basel.

Future Directions for the Early Detection of Recurrent Breast Cancer

PubMed Central

Schneble, Erika J.; Graham, Lindsey J.; Shupe, Matthew P.; Flynt, Frederick L.; Banks, Kevin P.; Kirkpatrick, Aaron D.; Nissan, Aviram; Henry, Leonard; Stojadinovic, Alexander; Shumway, Nathan M.; Avital, Itzhak; Peoples, George E.; Setlik, Robert F.

2014-01-01

The main goal of follow-up care after breast cancer treatment is the early detection of disease recurrence. In this review, we emphasize the multidisciplinary approach to this continuity of care from surgery, medical oncology, and radiology. Challenges within each setting are briefly addressed as a means of discussion for the future directions of an effective and efficient surveillance plan of post-treatment breast cancer care. PMID:24790657

Blueprint of quartz crystal microbalance biosensor for early detection of breast cancer through salivary autoantibodies against ATP6AP1.

PubMed

Arif, Sania; Qudsia, Syeda; Urooj, Samina; Chaudry, Nazia; Arshad, Aneeqa; Andleeb, Saadia

2015-03-15

Breast cancer represents a significant health problem because of its high prevalence. Tests like mammography, which are used abundantly for the detection of breast cancer, suffer from serious limitations. Mammography correctly detects malignancy about 80-90% of the times, failing in places when (1) the tumor is small at early stage, (2) breast tissue is dense or (3) in women of less than 40 years. Serum-based detection of biomarkers involves risk of disease transfer, along with other concerns. These techniques compromise in the early detection of breast cancer. Early detection of breast cancer is a crucial factor to enhance the survival rate of patient. Development of regular screening tests for early diagnosis of breast cancer is a challenge. This review highlights the design of a handy and household biosensor device aimed for self-screening and early diagnosis of breast cancer. The design makes use of salivary autoantibodies for specificity to develop a noninvasive procedure, breast cancer specific biomarkers for precision for the development of device, and biosensor technology for sensitivity to screen the early cases of breast cancer more efficiently. Copyright © 2014 Elsevier B.V. All rights reserved.

RELATIONSHIPS BETWEEN BREAST-FEEDING, CO-SLEEPING, AND SOMATIC COMPLAINTS IN EARLY CHILDHOOD.

PubMed

Peters, Elisabeth Maria; Lusher, Joanne Marie; Banbury, Samantha; Chandler, Chris

2016-09-01

The central aim of this study was to expand a limited body of knowledge on the complex relationship between breast-feeding, co-sleeping, and somatic complaints in early childhood. An opportunity sample of 98 parents from the general population with children aged 18 to 60 months consented to participate in the study. Each parent completed a series of questionnaires measuring somatic complaints, sleep problems, co-sleeping, breast-feeding, and demographic factors. Findings indicated that co-sleeping was associated with increased somatic complaints and that breast-feeding associated with decreased somatic complaints. Co-sleeping also was found to be associated with an increase in sleep problems. Boys demonstrated significantly higher levels of sleep problems than did girls. These findings highlight the relationship between co-sleeping during early childhood, which could have implications for prevention, treatment, and intervention regarding somatic complaints and sleep problems in early childhood. © 2016 Michigan Association for Infant Mental Health.

Comparison between early and late onset breast cancer in Pakistani women undergoing breast conservative therapy: is there any difference?

PubMed

Bhatti, Abu Bakar Hafeez; Jamshed, Aarif; Khan, Amina; Siddiqui, Neelam; Muzaffar, Nargis; Shah, Mazhar Ali

2014-01-01

Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ≤ 40 and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS) . For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

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

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

Regulation of miRNA-29c and its downstream pathways in preneoplastic progression of triple-negative breast cancer

PubMed Central

Bhardwaj, Anjana; Singh, Harpreet; Rajapakshe, Kimal; Tachibana, Kazunoshin; Ganesan, Nivetha; Pan, Yinghong; Gunaratne, Preethi H.; Coarfa, Cristian; Bedrosian, Isabelle

2017-01-01

Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth. miRNA-29c exerts its growth inhibitory effects through direct binding and regulation of TGFB-induced factor homeobox 2 (TGIF2), CAMP-responsive element binding protein 5 (CREB5), and V-Akt murine thymoma viral oncogene homolog 3 (AKT3). miRNA-29c regulation of these gene targets seems to be functionally relevant, as TGIF2, CREB5, and AKT3 were able to rescue the inhibition of cell proliferation and colony formation caused by ectopic expression of miRNA-29c in preneoplastic cells. AKT3 is an oncogene of known relevance in breast cancer, and as a proof of principle we show that inhibition of phosphoinositide 3-kinase (PI3K) activity, a protein upstream of AKT3, suppressed proliferation in TNBC preneoplastic cells. We explored additional opportunities for prevention of TNBC by studying the regulation of miRNA-29c and identified DNA methylation to have a role in the inhibition of miRNA-29c during TNBC tumorigenesis. Consistent with these observations, we found 5 aza-cytadine to relieve the suppression of miRNA-29c. Together, these results demonstrate that miRNA-29c loss plays a key role in the early development of TNBC. PMID:28160548

Early life residence, fish consumption and risk of breast cancer

PubMed Central

Haraldsdottir, Alfheidur; Steingrimsdottir, Laufey; Valdimarsdottir, Unnur A.; Aspelund, Thor; Tryggvadottir, Laufey; Harris, Tamara B.; Launer, Lenore J.; Mucci, Lorelei A.; Giovannucci, Edward L.; Adami, Hans-Olov; Gudnason, Vilmundur; Torfadottir, Johanna E.

2016-01-01

Background Little is known about fish intake throughout the life course and the risk of breast cancer. Methods We used data on the first residence of 9,340 women born 1908–1935 in the Reykjavik Study as well as food frequency data for different periods of life from a subgroup of the cohort entering the AGES-Reykjavik Study (n = 2,882). Results During a mean follow-up of 27.3 years, 744 women were diagnosed with breast cancer in the Reykjavik Study. An inverse association of breast cancer was observed among women who lived through the puberty period in coastal villages, compared with women residing in the capital area (HR = 0.78, 95% CI: 0.61, 0.99). In the subgroup analysis of this Icelandic population, generally characterized by high fish intake, we found an indication of lower risk of breast cancer among women with high fish consumption (more than 4 portions per week) in adolescence (HR 0.71, 95% CI, 0.44, 1.13) and midlife (HR 0.46, 95% CI, 0.22, 0.97), compared with low consumers (2 portions per week or less). No association was found for fish liver oil consumption in any time period which could be due to lack of a reference group with low omega-3 fatty acids intake in the study group. Conclusion Our findings suggest that very high fish consumption in early to midlife may be associated with a reduced risk of breast cancer. Impact Very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer. PMID:27765796

A microengineered pathophysiological model of early-stage breast cancer.

PubMed

Choi, Yoonseok; Hyun, Eunjeh; Seo, Jeongyun; Blundell, Cassidy; Kim, Hee Chan; Lee, Eunhee; Lee, Su Hyun; Moon, Aree; Moon, Woo Kyung; Huh, Dongeun

2015-08-21

A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease.

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

Does breast screening offer a survival benefit? A retrospective comparative study of oncological outcomes of screen-detected and symptomatic early stage breast cancer cases.

PubMed

Újhelyi, M; Pukancsik, D; Kelemen, P; Kovács, E; Kenessey, I; Udvarhelyi, N; Bak, M; Kovács, T; Mátrai, Z

2016-12-01

Mammography screening reduces breast cancer mortality by up to 32%. However, some recent studies have questioned the impact of non-palpable breast cancer detection on mortality reduction. The aim of this study was to analyse the clinicopathological and long-term follow-up data of early stage screened and symptomatic breast cancer patients. The institutional prospectively led database was systematically analysed for breast cancer cases diagnosed via the mammography screening program from 2002 to 2009. As a control group, symptomatic early stage breast cancer patients were collected randomly from the same database and matched for age and follow-up period. All medical records were reviewed retrospectively. Data from 298 breast cancer patients were collected from 47,718 mammography screenings. In addition, 331 symptomatic breast cancer patients were randomly selected. The screened group presented a significantly lower median tumour size (P < 0.00001). The incidence of negative regional lymph nodes was significantly higher in the screened group (P < 0.0006). The incidence of chemotherapy was 17% higher in the symptomatic group (P = 4*10 -5 ). At the median follow-up of 65 and 80 months, the screened group did not exhibit better overall (P = 0.717) or disease-free survival (P = 0.081) compared to the symptomatic group. Our results do not suggest that mammography screening does not reduce breast cancer mortality but the mammography screening did not bring any significant improvement in patient overall or disease-free survival for the early stage breast cancer patients compared to the symptomatic group. The drawback of symptomatic early stage tumours compared to non-palpable tumours could be equalized by modern multimodality oncology treatments. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

PubMed

Visvader, Jane E

2009-11-15

The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

Developing a discrete choice experiment in Malawi: eliciting preferences for breast cancer early detection services.

PubMed

Kohler, Racquel E; Lee, Clara N; Gopal, Satish; Reeve, Bryce B; Weiner, Bryan J; Wheeler, Stephanie B

2015-01-01

In Malawi, routine breast cancer screening is not available and little is known about women's preferences regarding early detection services. Discrete choice experiments are increasingly used to reveal preferences about new health services; however, selecting appropriate attributes that describe a new health service is imperative to ensure validity of the choice experiment. To identify important factors that are relevant to Malawian women's preferences for breast cancer detection services and to select attributes and levels for a discrete choice experiment in a setting where both breast cancer early detection and choice experiments are rare. We reviewed the literature to establish an initial list of potential attributes and levels for a discrete choice experiment and conducted qualitative interviews with health workers and community women to explore relevant local factors affecting decisions to use cancer detection services. We tested the design through cognitive interviews and refined the levels, descriptions, and designs. Themes that emerged from interviews provided critical information about breast cancer detection services, specifically, that breast cancer interventions should be integrated into other health services because asymptomatic screening may not be practical as an individual service. Based on participants' responses, the final attributes of the choice experiment included travel time, health encounter, health worker type and sex, and breast cancer early detection strategy. Cognitive testing confirmed the acceptability of the final attributes, comprehension of choice tasks, and women's abilities to make trade-offs. Applying a discrete choice experiment for breast cancer early detection was feasible with appropriate tailoring for a low-income, low-literacy African setting.

Awareness that early cancer lump is painless could decrease breast cancer mortality in developing countries.

PubMed

Garg, Pankaj

2016-06-10

There are several factors which contribute to patients' reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a warning sign of early breast cancer. This fact is significant because this could be one of the prime reasons for the women having discovered a painless lump in the breast, accidentally or by breast self-examination, presume it to be harmless and don't report early to health care facility. Therefore, creating awareness about ECLIPs could be an effective strategy to reduce mortality due to breast cancer in low- and middle-income countries. Moreover, unlike modifying risk factors which requires long term behavior modification, creating awareness about ECLIPs is easy and cost effective.

Glyceollin, a novel regulator of mTOR/p70S6 in estrogen receptor positive breast cancer

USDA-ARS?s Scientific Manuscript database

An estimated 70% of breast cancer tumors utilize estrogen receptor (ER) signaling to maintain tumorigenesis, and targeting of the estrogen receptor is a common method of treatment for these tumor types. However, ER-positive (+) breast cancers often acquire drug resistant or altered ER activity in r...

Cosmetic Outcome and Seroma Formation After Breast-Conserving Surgery With Intraoperative Radiation Therapy Boost for Early Breast Cancer

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

Senthi, Sashendra, E-mail: sashasenthi@msn.com; Link, Emma; Chua, Boon H.

2012-10-01

Purpose: To evaluate cosmetic outcome and its association with breast wound seroma after breast-conserving surgery (BCS) with targeted intraoperative radiation therapy (tIORT) boost for early breast cancer. Methods and Materials: An analysis of a single-arm prospective study of 55 patients with early breast cancer treated with BCS and tIORT boost followed by conventional whole breast radiation therapy (WBRT) between August 2003 and January 2006 was performed. A seroma was defined as a fluid collection at the primary tumor resection site identified clinically or radiologically. Cosmetic assessments using the European Organization for Research and Treatment of Cancer rating system were performedmore » at baseline before BCS and 30 months after WBRT was completed. Results: Twenty-eight patients (51%) developed a seroma, with 18 patients (33%) requiring at least 1 aspiration. Tumor location was significantly associated with seroma formation (P=.001). Ten of 11 patients with an upper inner quadrant tumor developed a seroma. Excellent or good overall cosmetic outcome at 30 months was observed in 34 patients (62%, 95% confidence interval 53%-80%). Seroma formation was not associated with the overall cosmetic result (P=.54). Conclusion: BCS with tIORT boost followed by WBRT was associated with an acceptable cosmetic outcome. Seroma formation was not significantly associated with an adverse cosmetic outcome.« less

Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation

DTIC Science & Technology

2008-03-01

CONTRACT NUMBER Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation...research proposed here can directly lead to clinical improvements in both early breast cancer detection, as well as effective breast cancer therapy. To date... cancer is a major prognostic factor in the management of the disease. In particular, detecting breast cancer in its pre-invasive form as ductal carcinoma

The role of BRCA1 in homologous recombination repair in response to replication stress: significance in tumorigenesis and cancer therapy

PubMed Central

2013-01-01

Germ line mutations in breast cancer gene 1 (BRCA1) predispose women to breast and ovarian cancers. Although BRCA1 is involved in many important biological processes, the function of BRCA1 in homologous recombination (HR) mediated repair is considered one of the major mechanisms contributing to its tumor suppression activity, and the cause of hypersensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors when BRCA1 is defective. Mounting evidence suggests that the mechanism of repairing DNA double strand breaks (DSBs) by HR is different than the mechanism operating when DNA replication is blocked. Although BRCA1 has been recognized as a central component in HR, the precise role of BRCA1 in HR, particularly under replication stress, has remained largely unknown. Given the fact that DNA lesions caused by replication blockages are the primary substrates for HR in mitotic cells, functional analysis of BRCA1 in HR repair in the context of replication stress should benefit our understanding of the molecular mechanisms underlying tumorigenesis associated with BRCA1 deficiencies, as well as the development of therapeutic approaches for cancer patients carrying BRCA1 mutations or reduced BRCA1 expression. This review focuses on the current advances in this setting and also discusses the significance in tumorigenesis and cancer therapy. PMID:23388117

Breast cancer metastasis to the stomach resembling early gastric cancer.

PubMed

Eo, Wan Kyu

2008-12-01

Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast.

The incidence of bone metastasis after early-stage breast cancer in Canada.

PubMed

Liede, Alexander; Jerzak, Katarzyna J; Hernandez, Rohini K; Wade, Sally W; Sun, Ping; Narod, Steven A

2016-04-01

Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

The Impact of Radiation Oncologists on the Early Adoption of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer.

PubMed

Boero, Isabel J; Gillespie, Erin F; Hou, Jiayi; Paravati, Anthony J; Kim, Ellen; Einck, John P; Yashar, Catheryn; Mell, Loren K; Murphy, James D

2017-03-01

Despite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer. We identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy. Among the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P<.05). The individual radiation oncologist strongly influenced the likelihood of a patient

Early discharge with tube feeding at home for preterm infants is associated with longer duration of breast feeding.

PubMed

Meerlo-Habing, Z E; Kosters-Boes, E A; Klip, H; Brand, P L P

2009-07-01

Mothers of preterm infants are more likely to discontinue breast feeding early than mothers of term infants. We evaluated the effect of early discharge with tube feeding of preterm infants under close supervision by paediatric nurse specialists on the duration of breast feeding. Case-control study. Medium/high-care neonatal unit of a large district general hospital. Preterm infants (<37 weeks' gestational age). Early discharge with tube feeding under close supervision by paediatric nurse specialists or regular follow-up of preterm infants discharged with oral feeding. Duration of breast feeding assessed by telephone interview 6 months after birth. There were 50 preterm infants in the early discharge group and 78 in the control group. Mothers in the early discharge group continued to breast feed longer than mothers in the control group (log rank test, p = 0.028). Four months after discharge, 63% of preterm infants in the control group were fed formula compared to 36% in the early discharge group (95% CI for difference 9% to 43%, p = 0.04). The relative risk of breast feeding cessation 6 months after birth in the early discharge group compared to the control group was 0.63 (95% CI 0.41 to 0.96). After adjustment for smoking, gestational age and birth weight, this relative risk was 0.67 (95% CI 0.43 to 1.05). Close supervision and follow-up by paediatric nurse specialists of preterm infants discharged early with tube feeding appears to increase duration of breast feeding. A randomised controlled trial to confirm these findings is warranted.

Can we prevent BRCA1-associated breast cancer by RANKL inhibition?

PubMed

Kotsopoulos, Joanne; Singer, Christian; Narod, Steven A

2017-01-01

BRCA1 mutation carriers face a high lifetime risk of breast cancer, estimated at 60 % compared to 10 % in the general population. BRCA1 breast cancers typically have an aggressive course (i.e., high-grade, triple-negative) and are associated with a poor prognosis. At present, primary prevention is limited to prophylactic removal of the unaffected breasts. Effective chemopreventive strategies are not yet available. Emerging evidence suggests that BRCA1 mutation carriers have high circulating levels of progesterone which may play a role in their susceptibility to breast cancer. Recently, the RANK/RANKL system was found to be dysregulated in women with a BRCA1 mutation. Mutation carriers had significantly lower endogenous levels of osteoprotegerin (OPG) than women without a BRCA1 mutation. OPG is an endogenous decoy receptor for RANKL and inhibits RANKL-mediated signaling. RANKL binds to RANK on mammary epithelial cells and stimulates their proliferation and maturation. Low OPG levels may contribute to mammary tumorigenesis through increased proliferation and may explain in part the increased breast cancer risk in BRCA1 mutation carriers. Denosumab is an anti-RANKL monoclonal antibody which is approved to treat osteoporosis and to prevent skeletal damage caused by bone metastases. The emerging role of aberrant RANK-signaling in BRCA1 tumorigenesis suggests that targeting of RANKL may prevent breast cancer among women with germline BRCA1 mutations. Clinical investigations of denosumab are warranted and may lead to a novel chemopreventive approach for breast cancer for high-risk women.

A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast cancer patients impairs its activity and is associated with increased breast cancer risk.

PubMed

Wang, N; Ding, H; Liu, C; Li, X; Wei, L; Yu, J; Liu, M; Ying, M; Gao, W; Jiang, H; Wang, Y

2015-10-01

Certain predisposition factors such as BRCA1/2 and CHEK2 mutations cause familial breast cancers that occur early. In China, breast cancers are diagnosed at relatively younger age, and higher percentage of patients are diagnosed before 40 years, than that in Caucasians. However, the prevalence for BRCA1/2 mutations and reported CHEK2 germline mutations is much lower or absent in Chinese population, arguing for the need to study other novel risk alleles among Chinese breast cancer patients. In this study, we searched for CHEK2 mutations in young, high-risk breast cancer patients in China and detected a missense variant Y390C (1169A > G) in 12 of 150 patients (8.0%) and 2 in 250 healthy controls (0.8%, P = 0.0002). Four of the Y390C carriers have family history of breast and/or ovarian cancer. In patients without family history, Y390C carriers tend to develop breast cancer early, before 35 years of age. The codon change at Y390, a highly conserved residue located in CHEK2's kinase domain, appeared to significantly impair CHEK2 activity. Functional analysis suggested that the CHEK2 Y390C mutation is deleterious as judged by the mutant protein's inability to inactivate CDC25A or to activate p53 after DNA damage. Cells expressing the CHEK2 Y390C variant showed impaired p21 and Puma expression after DNA damage, and the deregulated cell cycle checkpoint and apoptotic response may help conserve mutations and therefore contribute to tumorigeneisis. Taken together, our results not only identified a novel CHEK2 allele that is associated with cancer families and confers increased breast cancer risk, but also showed that this allele significantly impairs CHEK2 function during DNA damage response. Our results provide further insight on how the function of such an important cancer gene may be impaired by existing mutations to facilitate tumorigenesis. It also offers a new subject for breast cancer monitoring, prevention and management.

Weight changes after adjuvant treatment in Korean women with early breast cancer.

PubMed

Han, Hye-Suk; Lee, Keun-Wook; Kim, Jee Hyun; Kim, Sung-Won; Kim, In-Ah; Oh, Do-Youn; Im, Seock-Ah; Bang, Soo-Mee; Lee, Jong Seok

2009-03-01

Weight gain is a common problem in breast cancer patients and is reported to be associated with poorer survival. However, most data are limited to Western women. We evaluated weight changes after adjuvant treatment in Korean women with early breast cancer. The authors reviewed the records of 260 patients with stage I-III breast cancer treated between June 2003 and February 2006. Body weight, body mass index (BMI) and menopausal status at baseline and after 3, 6, 12 and 24 months of adjuvant treatment were reviewed. Mean patient age was 47.0 years and 61.1% of women were premenopausal. Among them, 195 patients (75.8%) received chemotherapy and 186 (71.5%) received hormonal therapy. Mean baseline weight was 57.5 +/- 9.8 kg and mean BMI was 23.5 +/- 1.6 kg/m(2) (22.8 +/- 3.0 vs. 24.7 +/- 3.2 kg/m(2) for pre- vs. post-menopausal women, P = 0.286). Mean weight changes were; 0.30 kg at 3 months (P = 0.019); 0.16 kg at 6 months (P = 0.367); -0.34 kg at 1 year (P = 0.082); -0.40 kg at 2 years (P = 0.097). Twenty-three patients (10.4%) gained more than 5% of baseline body weight at 1 year, but no clinical variable was found to be associated with these weight gains. This study shows that Korean women with early breast cancer do not gain weight after adjuvant treatment. Further studies are needed to determine differences between Asian and Western women in terms of weight changes and prognosis in early breast cancer.

Depression and anxiety in women with early breast cancer: five year observational cohort study

PubMed Central

Burgess, Caroline; Cornelius, Victoria; Love, Sharon; Graham, Jill; Richards, Michael; Ramirez, Amanda

2005-01-01

Objective To examine the prevalence of, and risk factors for, depression and anxiety in women with early breast cancer in the five years after diagnosis. Design Observational cohort study. Setting NHS breast clinic, London. Participants 222 women with early breast cancer: 170 (77%) provided complete interview data up to either five years after diagnosis or recurrence. Main outcome measures Prevalence of clinically important depression and anxiety (structured psychiatric interview with standardised diagnostic criteria) and clinical and patient risk factors, including stressful life experiences (Bedford College life events and difficulties schedule). Results Nearly 50% of the women with early breast cancer had depression, anxiety, or both in the year after diagnosis, 25% in the second, third, and fourth years, and 15% in the fifth year. Point prevalence was 33% at diagnosis, falling to 15% after one year. 45% of those with recurrence experienced depression, anxiety, or both within three months of the diagnosis. Previous psychological treatment predicted depression, anxiety, or both in the period around diagnosis (one month before diagnosis to four months after diagnosis). Longer term depression and anxiety, were associated with previous psychological treatment, lack of an intimate confiding relationship, younger age, and severely stressful non-cancer life experiences. Clinical factors were not associated with depression and anxiety, at any time. Lack of intimate confiding support also predicted more protracted episodes of depression and anxiety. Conclusion Increased levels of depression, anxiety, or both in the first year after a diagnosis of early breast cancer highlight the need for dedicated service provision during this time. Psychological interventions for women with breast cancer who remain disease free should take account of the broader social context in which the cancer occurs, with a focus on improving social support. PMID:15695497

Women with breast cancer: self-reported distress in early survivorship.

PubMed

Lester, Joanne; Crosthwaite, Kara; Stout, Robin; Jones, Rachel N; Holloman, Christopher; Shapiro, Charles; Andersen, Barbara L

2015-01-01

To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. Descriptive, cross-sectional. A National Cancer Institute-designated comprehensive cancer center. 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. Distress scores, problem reports, and time groups. Participants scored in range of the cutoff of more than 4 (range = 4.1-5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. Interventions to reduce or prevent distress may improve outcomes in early survivorship.

BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico.

PubMed

Ruiz-Flores, Pablo; Sinilnikova, Olga M; Badzioch, Michael; Calderon-Garcidueñas, A L; Chopin, Sandrine; Fabrice, Odefrey; González-Guerrero, J F; Szabo, Csilla; Lenoir, Gilbert; Goldgar, David E; Barrera-Saldaña, Hugo A

2002-12-01

The entire coding regions of BRCA1 and BRCA2 were screened for mutations by heteroduplex analysis in 51 Mexican breast cancer patients. One BRCA1 and one BRCA2 truncating mutation each was identified in the group of 32 (6%) early-onset breast cancer patients (< or =35 years). Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case. No mutations or rare sequence variants have been identified in two additional families including each an early-onset breast cancer case and an ovarian cancer patient. The two truncating mutations (BRCA1 3857delT; BRCA2 2663-2664insA) and six of the rare variants have never been reported before and may be of country-specific origin. The majority of the alterations appeared to be distinct, with only one of them being observed in more than one family. Copyright 2002 Wiley-Liss, Inc.

Prognosis for Mammographically Occult, Early-Stage Breast Cancer Patients Treated With Breast-Conservation Therapy

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

Yang, Tzu-I. J.; Yang Qifeng; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan

2010-01-15

Purpose: To compare mammographically occult (MamOcc) and mammographically positive (MamPos) early-stage breast cancer patients treated with breast-conservation therapy (BCT), to analyze differences between the two cohorts. Methods and Materials: Our two cohorts consisted of 214 MamOcc and 2168 MamPos patients treated with BCT. Chart reviews were conducted to assess mammogram reports and method of detection. All clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. Results: Median follow-up was 7 years. There were no differences in final margins, T stage, nodal status, estrogen/progesterone receptor status, or 'triple-negative' status. Significant differences included younger age at diagnosis (pmore » < 0.0001), more positive family history (p = 0.0033), less HER-2+ disease (p = 0.0294), and 1{sup o} histology (p < 0.0001). At 10 years, the differences in overall survival, cause-specific survival, and distant relapse between the two groups did not differ significantly. The MamOcc cohort had more breast relapses (15% vs. 8%; p = 0.0357), but on multivariate analysis this difference was not significant (hazard ratio 1.0, 95% confidence interval 0.993-1.007, p = 0.9296). Breast relapses were mammographically occult in 32% of the MamOcc and 12% of the MamPos cohorts (p = 0.0136). Conclusions: Although our study suggests that there are clinical-pathologic variations for the MamOcc cohort vs. MamPos patients that may ultimately affect management, breast relapse after BCT was not significantly different. Breast recurrences were more often mammographically occult in the MamOcc cohort; consideration should be given to closer follow-up and alternative imaging strategies (ultrasound, breast MRI) for routine posttreatment examination. To our knowledge, this represents the largest series addressing the prognostic significance of MamOcc cancers treated with BCT.« less

Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors

DTIC Science & Technology

2014-10-01

confer stemness . We hypothesize that inhibition of IKK/NF-κB will reduce or eliminate breast camcer TICs, blocking tumorigenesis. Furthermore, we...Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011 Oct;121(10):3804-9. Review...cells and sub- population of cells termed cancer stem cells or tumor-initiating cells (TICs).1 The primary characteristic of TICs is their ability to

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression

PubMed Central

Suchanski, Jaroslaw; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Owczarek, Tomasz; Kruczak, Anna; Ambicka, Aleksandra; Rys, Janusz; Ugorski, Maciej; Podhorska-Okolow, Marzena; Dziegiel, Piotr

2015-01-01

It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients’ shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases. PMID:25933064

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis

PubMed Central

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P.; Fulzele, Sadanand; Pei, Lirong; Chang, Chang-Sheng; Choi, Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D.; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-01-01

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumors, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumors and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment. PMID:25908435

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis.

PubMed

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P; Sadanand, Fulzele; Pei, Lirong; Chang, Chang-Sheng; Choi, Jeong-Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-04-24

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumours, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumours and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment.

Breast Cancer: subgroups specific blood-biomarkers for early / predictive diagnosis and personalized treatment — EDRN Public Portal

Cancer.gov

Breast-conserving lumpectomy followed by radiation therapy has been shown to be an alternative strategy, competitive to mastectomy, in preventing mortality caused by breast cancer. However, besides negative short-term effects (blood flow disturbances, painful erythema, etc.) breast irradiation causes severe long-term side-effects (leucopenia, anemia, breast edema, fibrosis, increase of angiosarcoma, leukemia, myelodysplastic syndromes). Therefore, the identification of individual susceptibility to radiation and improved patient-specific radiotherapy planning are highly desirable for personalised treatment in breast cancer. Why early and predictive diagnosis is crucial for long-term outcomes of breast cancer? Breast cancer is the most common cause of cancer death among women with an average incidence rate of 10-12 per 100 women. In 2005, breast cancer led to 502,000 deaths worldwide. Advanced stages of breast cancer lead to the development of metastasis predominantly in the lymph nodes, bone, lung, skin, brain, and liver. Although breast-MRI is currently the most sensitive diagnostic tool for breast imaging, its specificity is limited resulting in a negative impact for surgical management in approximately 9 % of cases. Early diagnosis has been demonstrated to be highly beneficial, enabling significantly enhanced therapy efficiency and possibly full recovery.

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

PubMed

Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

2018-05-01

The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.

PubMed

Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions.

[China expert consensus on the management of dyslipidemia in postmenopausal patients with early-stage breast cancer].

PubMed

2017-01-23

Estrogen has an impact on the type of lipoproteins and the blood lipid levels, thus protecting the cardiovascular system. Postmenopausal breast cancer patients suffer a significant decrease in estrogen levels due to both physiological changes and the use of drugs, and thus have a higher risk of atherosclerotic cardiovascular diseases. Therefore, strict lipid management is required for postmenopausal breast cancer patients receiving endocrine therapy. However, no guidelines have been developed in terms of lipid management and intervention for postmenopausal breast cancer patients. The Chinese expert group of multidisciplinary management of dyslipidemia in breast cancer patients with endocrine therapy, after deep investigation into the management of dyslipidemia in postmenopausal patients with early-stage breast cancer, has developed the China Expert Consensus on Dyslipidemia Management in Postmenopausal Patients with Early-stage Breast Cancer. The Consensus clearly defines the goals and measures of interventions for dyslipidemia, hoping to effectively reduce the risk of atherosclerotic cardiovascular disease in postmenopausal breast cancer patients and further improve the long-term survival of the patients.

The Mammary Stem Cell Hierarchy: A Looking Glass into Heterogeneous Breast Cancer Landscapes

PubMed Central

Sreekumar, Amulya; Roarty, Kevin; Rosen, Jeffrey M.

2015-01-01

The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types, and signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective. PMID:26206777

Predictors of axillary lymph node metastases in women with early breast cancer in Singapore.

PubMed

Tan, L G L; Tan, Y Y; Heng, D; Chan, M Y

2005-12-01

The presence of axillary lymph node metastases is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla. It is hoped that with SLNB, the morbidity from axillary lymph node dissection (ALND) can be avoided without compromising the staging and management of early breast cancer. However, only patients found to be SLNB negative benefit from this procedure, as those with positive SLNB may still require ALND. Our objective is to study the various clinico-pathological factors to find predictive factors for axillary lymph node involvement in early breast cancer. It is hoped that with these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. A retrospective study of 380 early breast cancer cases (stage T1 and T2, N0, N1, M0) in women treated in the Department of General Surgery, Tan Tock Seng Hospital, between January 1999 and August 2002, was conducted. Incidence of nodal metastases was correlated with clinico-pathological factors, and analysed by univariate and multivariate analyses. Approximately 35 percent of the 380 cases of early breast cancer had nodal metastases. Multivariate analyses revealed four independent predictors of node positivity: tumour size (p-value equals 0.0001), presence of lymphovascular invasion (p-value is less than 0.0001), tumours with histology other than invasive ductal or lobular carcinoma (p-value equals 0.04), and presence of progesterone receptors (p-value equals 0.05). We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling.

Breast Density Notification Legislation and Breast Cancer Stage at Diagnosis: Early Evidence from the SEER Registry.

PubMed

Richman, Ilana; Asch, Steven M; Bendavid, Eran; Bhattacharya, Jay; Owens, Douglas K

2017-06-01

Twenty-eight states have passed breast density notification laws, which require physicians to inform women of a finding of dense breasts on mammography. To evaluate changes in breast cancer stage at diagnosis after enactment of breast density notification legislation. Using a difference-in-differences analysis, we examined changes in stage at diagnosis among women with breast cancer in Connecticut, the first state to enact legislation, compared to changes among women in control states. We used data from the Surveillance, Epidemiology, and End Results Program (SEER) registry, 2005-2013. Women ages 40-74 with breast cancer. Breast density notification legislation, enacted in Connecticut in October of 2009. Breast cancer stage at diagnosis. Our study included 466,930 women, 25,592 of whom lived in Connecticut. Legislation was associated with a 1.38-percentage-point (95 % CI 0.12 to 2.63) increase in the proportion of women in Connecticut versus control states who had localized invasive cancer at the time of diagnosis, and a 1.12-percentage-point (95 % CI -2.21 to -0.08) decline in the proportion of women with ductal carcinoma in situ at diagnosis. Breast density notification legislation was not associated with a change in the proportion of women in Connecticut versus control states with regional-stage (-0.09 percentage points, 95 % CI -1.01 to 1.02) or metastatic disease (-0.24, 95 % CI -0.75 to 0.28). County-level analyses and analyses limited to women younger than 50 found no statistically significant associations. Single intervention state, limited follow-up, potential confounding from unobserved trends. Breast density notification legislation in Connecticut was associated with a small increase in the proportion of women diagnosed with localized invasive breast cancer in individual-level but not county-level analyses. Whether this finding reflects potentially beneficial early detection or potentially harmful overdiagnosis is not known. Legislation was not

Fbxw7 Tumor Suppressor: A Vital Regulator Contributes to Human Tumorigenesis

PubMed Central

Cao, Jun; Ge, Ming-Hua; Ling, Zhi-Qiang

2016-01-01

Abstract Rapidly accumulating data indicate that F-box/WD repeat-containing protein 7 (Fbxw7) is one of the most frequently mutated genes in human cancers and regulates a network of crucial oncoproteins. These studies have generated important new insights into tumorigenesis and may soon enable therapies targeting the Fbxw7 pathway. We searched PubMed, Embase, and ISI Web of Science databases (1973–2015, especially recent 5 years) for articles published in the English language using the key words “Fbxw7,” “Fbw7,” “hCDC4,” and “Sel-10,” and we reviewed recent developments in the search for Fbxw7. Fbxw7 coordinates the ubiquitin-dependent proteolysis of several critical cellular regulators, thereby controlling essential processes, such as cell cycle, differentiation, and apoptosis. Fbxw7 contains 3 isoforms (Fbxw7α, Fbxw7β, and Fbxw7γ), and they are differently regulated in subtract recognition. Besides those, Fbxw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates in a variety of human solid tumor types, including glioma malignancy, nasopharyngeal carcinoma, osteosarcoma, melanoma as well as colorectal, lung, breast, gastric, liver, pancreatic, renal, prostate, endometrial, and esophageal cancers. Fbxw7 is strongly associated with tumorigenesis, and the mechanisms and consequences of Fbxw7 deregulation in cancers may soon enable the development of novel therapeutic approaches. PMID:26886596

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

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

Nichols, Elizabeth, E-mail: Enichols1@umm.edu; Kesmodel, Susan B.; Bellavance, Emily

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures.more » A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy−APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.« less

Effect of maternal Chlorella supplementation on carotenoid concentration in breast milk at early lactation.

PubMed

Nagayama, Junya; Noda, Kiyoshi; Uchikawa, Takuya; Maruyama, Isao; Shimomura, Hiroshi; Miyahara, Michiyoshi

2014-08-01

Breast milk carotenoids provide neonates with a source of vitamin A and potentially, oxidative stress protection and other health benefits. Chlorella, which has high levels of carotenoids such as lutein, zeaxanthin and β-carotene, is an effective dietary source of carotenoids for humans. In this study, the effect of maternal supplementation with Chlorella on carotenoid levels in breast milk at early lactation was investigated. Ten healthy, pregnant women received 6 g of Chlorella daily from gestational week 16-20 until the day of delivery (Chlorella group); ten others did not (control group). Among the carotenoids detected in breast milk, lutein, zeaxanthin and β-carotene concentrations in the Chlorella group were 2.6-fold (p = 0.001), 2.7-fold (p = 0.001) and 1.7-fold (p = 0.049) higher, respectively, than those in the control group. Our study shows that Chlorella intake during pregnancy is effective in improving the carotenoid status of breast milk at early lactation.

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

Through the looking glass at early-life exposures and breast cancer risk.

PubMed

Forman, Michele R; Cantwell, Marie M; Ronckers, Cécile; Zhang, Yawei

2005-01-01

The global increase in the proportion of women diagnosed with breast cancer, inadequate access to screening and high cost of treatment for breast cancer argue strongly for a greater focus on preventive strategies. But at what age is it appropriate to begin targeting preventive approaches? The recognized role of perinatal nutrition in neurologic development and the relation of maternal nutritional status to birthweight and subsequent risk of hypertension, diabetes, and cardiovascular disease identify pregnancy and early childhood as potential phases for prevention. This review examines indicators of hormonal and nutritional exposures in early life and breast cancer risk through the lens of the life course paradigm integrated with maternal and child health research and methodology. Compared to women who were normal birthweight (2500-3999 g), women who weighed>or=4,000 g at birth have a 20 percent to 5-fold increased risk of premenopausal breast cancer. Women born preterm and likely to be small- or large-for-date also have an increased risk. Birth length is directly associated with risk and has a larger magnitude of effect than birthweight. Prior preeclamptics and their daughters have a lower risk of breast cancer than comparable normotensives. An association between infant feeding practices and breast cancer is unclear without improved exposure assessment and analysis. Rapid childhood and pubertal linear growth increases breast cancer risk, while greater body fat over the same periods reduces risk. Growth data thus far have not been calculated in Z-scores from reference growth curves for comparison across studies. Events and secular trends influencing birth cohorts may not be adequately addressed, thereby limiting the interpretation and implications of the findings. Research in nonhuman primates may help uncover underlying mechanisms.

77 FR 60703 - Breast and Cervical Cancer Early Detection and Control Advisory Committee: Notice of Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee: Notice of Charter Renewal This gives notice under the Federal Advisory Committee Act (Pub. L. 92-463) of October 6, 1972, that the Breast and Cervical Cancer Early Detection and Control...

YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma.

PubMed

Yang, Chao; Tan, Juan; Zhu, Jun; Wang, Shan; Wei, Guanghui

2017-06-06

The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors. Additionally, less proliferative and more apoptotic cells were found in the Peptide 17 treatment group. Furthermore, YAP inhibition significantly inhibited cisplatin-resistant neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The combination of Peptide 17 with low-dose cisplatin efficiently impaired cisplatin-resistant NB subcutaneous tumor growth, being as effective as high-dose cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice compared to the high-dose cisplatin treatment group. Collectively, this work identifies YAP as a novel regulator of neuroblastoma proliferation, tumorigenesis, and invasion and indicates that YAP is a potential therapeutic target for cisplatin-resistant neuroblastoma.

Women With Breast Cancer: Self-Reported Distress in Early Survivorship

PubMed Central

Lester, Joanne; Crosthwaite, Kara; Stout, Robin; Jones, Rachel N.; Holloman, Christopher; Shapiro, Charles; Andersen, Barbara L.

2015-01-01

Purpose/Objectives To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. Design Descriptive, cross-sectional. Setting A National Cancer Institute–designated comprehensive cancer center. Sample 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. Methods Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. Main Research Variables Distress scores, problem reports, and time groups. Findings Participants scored in range of the cutoff of more than 4 (range = 4.1–5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). Conclusions Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. Implications for Nursing Interventions to reduce or prevent distress may improve outcomes in early survivorship. PMID:25542330

[Imaging of breast tissues changes--early detection, screening and problem solving].

PubMed

Wruk, Daniela

2008-04-01

In the industrialised countries breast cancer is the cancer with the highest prevalence and causes the highest rate of cancer deaths among women. In Switzerland alone, about 5000 newly diagnosed cases occur per year. Our three main diagnostic tools in imaging diseases of the breast in the setting of screening, early detection or problem solving are mammography, ultrasound and MRI with intravenous contrast application. The most important imaging technique is mammography, which as only method has shown evidence to be suitable for screening so far. As a major accomplishing imaging tool there is sonography, which in women under 30 years of age is the first method of choice in examination of the breasts. The MRI is able to provide additional information about the perfusion of tissue changes within the breast; because of its low specificity, however, it should cautiously be applied for specific questions.

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

PubMed

Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

2018-05-01

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Time Interval From Breast-Conserving Surgery to Breast Irradiation in Early Stage Node-Negative Breast Cancer: 17-Year Follow-Up Results and Patterns of Recurrence

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

Vujovic, Olga, E-mail: olga.vujovic@lhsc.on.ca; Yu, Edward; Cherian, Anil

Purpose: A retrospectivechart review was conducted to determine whether the time interval from breast-conserving surgery to breast irradiation (surgery-radiation therapy interval) in early stage node-negative breast cancer had any detrimental effects on recurrence rates. Methods and Materials: There were 566 patients with T1 to T3, N0 breast cancer treated with breast-conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery-to-radiation therapy intervals used for analysis were 0 to 8 weeks (201 patients), >8 to 12 weeks (233 patients), >12 to 16 weeks (91 patients), and >16 weeks (41 patients). Kaplan-Meier estimates of time to local recurrence, disease-free survival, distantmore » disease-free survival, cause-specific survival, and overall survival rates were calculated. Results: Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of characteristics and pathologic features. There were no statistically significant differences among the 4 time groups in local recurrence (P=.67) or disease-free survival (P=.82). The local recurrence rates at 5, 10, and 15 years were 4.9%, 11.5%, and 15.0%, respectively. The distant disease relapse rates at 5, 10, and 15 years were 10.6%, 15.4%, and 18.5%, respectively. The disease-free failure rates at 5, 10, and 15 years were 20%, 32.3%, and 39.8%, respectively. Cause-specific survival rates at 5, 10, and 15 years were 92%, 84.6%, and 79.8%, respectively. The overall survival rates at 5, 10, and 15 years were 89.3%, 79.2%, and 66.9%, respectively. Conclusions: Surgery-radiation therapy intervals up to 16 weeks from breast-conserving surgery are not associated with any increased risk of recurrence in early stage node-negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.« less

The Breast and Cervical Cancer Early Detection Program, Medicaid, and breast cancer outcomes among Ohio's underserved women.

PubMed

Koroukian, Siran M; Bakaki, Paul M; Htoo, Phyo Than; Han, Xiaozhen; Schluchter, Mark; Owusu, Cynthia; Cooper, Gregory S; Rose, Johnie; Flocke, Susan A

2017-08-15

As an organized screening program, the national Breast and Cervical Cancer Early Detection Program (BCCEDP) was launched in the early 1990s to improve breast cancer outcomes among underserved women. To analyze the impact of the BCCEDP on breast cancer outcomes in Ohio, this study compared cancer stages and mortality across BCCEDP participants, Medicaid beneficiaries, and "all others." This study linked data across the Ohio Cancer Incidence Surveillance System, Medicaid, the BCCEDP database, death certificates, and the US Census and identified 26,426 women aged 40 to 64 years who had been diagnosed with incident invasive breast cancer during the years 2002-2008 (deaths through 2010). The study groups were as follows: BCCEDP participants (1-time or repeat users), Medicaid beneficiaries (women enrolled in Medicaid before their cancer diagnosis [Medicaid/prediagnosis] or around the time of their cancer diagnosis [Medicaid/peridiagnosis]), and all others (women identified as neither BCCEDP participants nor Medicaid beneficiaries). The outcomes included advanced-stage cancer at diagnosis and mortality. A multivariable logistic and survival analysis was conducted to examine the independent association between the BCCEDP and Medicaid status and the outcomes. The percentage of women presenting with advanced-stage disease was highest among women in the Medicaid/peridiagnosis group (63.4%) and lowest among BCCEDP repeat users (38.6%). With adjustments for potential confounders and even in comparison with Medicaid/prediagnosis beneficiaries, those in the Medicaid/peridiagnosis group were twice as likely to be diagnosed with advanced-stage disease (adjusted odds ratio, 2.20; 95% confidence interval, 1.83-2.66). Medicaid/peridiagnosis women are at particularly high risk to be diagnosed with advanced-stage disease. Efforts to reduce breast cancer disparities must target this group of women before they present to Medicaid. Cancer 2017;123:3097-106. © 2017 American Cancer Society

Human Chorionic Gonadotropin and Breast Cancer

PubMed Central

Schüler-Toprak, Susanne; Treeck, Oliver; Ortmann, Olaf

2017-01-01

Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy. PMID:28754015

Age, Comorbidity, and Breast Cancer Severity: Impact on Receipt of Definitive Local Therapy and Rate of Recurrence among Older Women with Early Stage Breast Cancer

PubMed Central

Field, Terry S; Bosco, Jaclyn LF; Prout, Marianne N; Gold, Heather T; Cutrona, Sarah; Pawloski, Pamala A; Yood, Marianne Ulcickas; Quinn, Virginia P; Thwin, Soe Soe; Silliman, Rebecca A

2011-01-01

Background The definitive local therapy options for early stage breast cancer are 1) mastectomy and 2) breast conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well studied Study Design In a cohort of 1837 women age≥65 years receiving treatment for early stage breast cancer in 6 integrated healthcare delivery systems in 1990–1994 and followed for 10 years, we examined predictors of receiving non-definitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. Results Age and comorbidity were associated with receipt of non-definitive therapy. Compared to those at low risk, women at the highest risk were less likely to receive non-definitive therapy (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.22, 0.47) while women at moderate risk were about half as likely (OR 0.54, CI 0.35, 0.84). Non-definitive local therapy was associated with higher rates of recurrence among women at moderate (HR 5.1, CI 1.9, 13.5) and low risk (HR 3.2, CI 1.1, 8.9). The association among women at high risk was weak (HR 1.3, CI 0.75, 2.1). Conclusions Among these older women with early stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence. PMID:22014658

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Cancer early detection program based on awareness and clinical breast examination: Interim results from an urban community in Mumbai, India.

PubMed

Gadgil, Anita; Sauvaget, Catherine; Roy, Nobhojit; Muwonge, Richard; Kantharia, Surita; Chakrabarty, Anuradha; Bantwal, Kanchan; Haldar, Indrani; Sankaranarayanan, Rengaswamy

2017-02-01

Indian women with breast cancer are usually diagnosed in advanced stages leading to poor survival. Improving breast awareness and increasing access to early diagnosis and adequate treatment has been advocated for breast cancer control. We implemented a program to increase awareness on breast cancer and access to its early detection in an occupational health care scheme in Mumbai, India. Breast awareness brochures were mailed annually between June 2013 and June 2016 to a cohort of 22,500 eligible women aged 30-69 years old receiving universal health care from an occupational health care scheme comprising of primary health centres and a referral secondary care hospital in Mumbai. Women with suspected breast cancers were provided with diagnostic investigations and treatment. Socio-demographic information and tumour characteristics were compared between the breast awareness pre-intervention period (Jan 2005-May 2013) and the breast awareness intervention period after four rounds of mailers (June 2013-June 2016). The proportion of women with early tumours and axillary lymph node negative cancers increased from 74% to 81% and 46% to 53% respectively, between the two periods. While the proportion of patients receiving breast conserving surgery increased from 39% to 51%, the proportion receiving chemotherapy decreased from 84% to 56%. Interim results following efforts to improve breast awareness and access to care in a cohort of women in an occupational health care scheme indicate early detection and more conservative treatment of breast cancers. Creating awareness and improving access to care may result in cancer down-staging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early Stage Breast Cancer in Older Women: Predictions and Outcomes of Therapy

DTIC Science & Technology

2000-10-01

found that the proportion of U.S. women with early stage breast cancer who are receiving appropriate care (defined by NIH Consensus statement) declined...surgery increased, and because women undergoing breast-conserving surgery are more likely to receive inappropriate care . We have now shown that patients... Care 2000;38:719-727. 6. Ann B. Nattinger’s Curriculum Vitae. 3 / Annual Report: Grant #DAMD17-96-1-6262 4.) INTRODUCTION Almost half of the incident

Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells

PubMed Central

Tenan, Mirna; Ferrari, Paolo; Sappino, André‐Pascal

2016-01-01

Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti‐acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long‐term exposure to concentrations of aluminium—in the form of aluminium chloride (AlCl3)—in the range of those measured in the human breast, transform normal murine mammary gland (NMuMG) epithelial cells in vitro as revealed by the soft agar assay. Subcutaneous injections into three different mouse strains with decreasing immunodeficiency, namely, NOD SCID gamma (NSG), NOD SCID or nude mice, revealed that untreated NMuMG cells form tumors and metastasize, to a limited extent, in the highly immunodeficient and natural killer (NK) cell deficient NSG strain, but not in the less permissive and NK cell competent NOD SCID or nude strains. In contrast, NMuMG cells transformed in vitro by AlCl3 form large tumors and metastasize in all three mouse models. These effects correlate with a mutagenic activity of AlCl3. Our findings demonstrate for the first time that concentrations of aluminium in the range of those measured in the human breast fully transform cultured mammary epithelial cells, thus enabling them to form tumors and metastasize in well‐established mouse cancer models. Our observations provide experimental evidence that aluminium salts could be environmental breast carcinogens. PMID:27541736

76 FR 55915 - Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection and Control Advisory... Secretary for Health, and the CDC on the early detection and control of breast and cervical cancer. The role...

VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis.

PubMed

Seagroves, Tiffany N; Peacock, Danielle L; Liao, Debbie; Schwab, Luciana P; Krueger, Robin; Handorf, Charles R; Haase, Volker H; Johnson, Randall S

2010-05-01

Overexpression of hypoxia inducible factor-1 (HIF-1)alpha, which is common in most solid tumors, correlates with poor prognosis and high metastatic risk in breast cancer patients. Because HIF-1alpha protein stability is tightly controlled by the tumor suppressor von Hippel-Lindau (VHL), deletion of VHL results in constitutive HIF-1alpha expression. To determine whether VHL plays a role in normal mammary gland development, and if HIF-1alpha overexpression is sufficient to initiate breast cancer, Vhl was conditionally deleted in the mammary epithelium using the Cre/loxP system. During first pregnancy, loss of Vhl resulted in decreased mammary epithelial cell proliferation and impaired alveolar differentiation; despite these phenotypes, lactation was sufficient to support pup growth. In contrast, in multiparous dams, Vhl(-/-) mammary glands exhibited a progressive loss of alveolar epithelium, culminating in lactation failure. Deletion of Vhl in the epithelium also impacted the mammary stroma, as there was increased microvessel density accompanied by hemorrhage and increased immune cell infiltration. However, deletion of Vhl was not sufficient to induce mammary tumorigenesis in dams bred continuously for up to 24 months of age. Moreover, co-deletion of Hif1a could not rescue the Vhl(-/-)-dependent phenotype as dams were unable to successfully lactate during the first lactation. These results suggest that additional VHL-regulated genes besides HIF1A function to maintain the proliferative and regenerative potential of the breast epithelium.

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing

PubMed Central

Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions. PMID:29344267

Stromal cells in breast cancer as a potential therapeutic target

PubMed Central

Dykes, Samantha S.; Hughes, Veronica S.; Wiggins, Jennifer M.; Fasanya, Henrietta O.; Tanaka, Mai; Siemann, Dietmar

2018-01-01

Breast cancer in the United States is the second most commonly diagnosed cancer in women. About 1 in 8 women will develop invasive breast cancer over the course of her lifetime and breast cancer remains the second leading cause of cancer-related death. In pursuit of novel therapeutic strategies, researchers have examined the tumor microenvironment as a potential anti-cancer target. In addition to neoplastic cells, the tumor microenvironment is composed of several critical normal cell types, including fibroblasts, vascular and lymph endothelial cells, osteoclasts, adipocytes, and immune cells. These cells have important roles in healthy tissue stasis, which frequently are altered in tumors. Indeed, tumor-associated stromal cells often contribute to tumorigenesis, tumor progression, and metastasis. Consequently, these host cells may serve as a possible target in anti-tumor and anti-metastatic therapeutic strategies. Targeting the tumor associated host cells offers the benefit that such cells do not mutate and develop resistance in response to treatment, a major cause of failure in cancer therapeutics targeting neoplastic cells. This review discusses the role of host cells in the tumor microenvironment during tumorigenesis, progression, and metastasis, and provides an overview of recent developments in targeting these cell populations to enhance cancer therapy efficacy.

A Simple System for the Early Detection of Breast Cancer

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-14-1-0231 TITLE: A Simple System for Early Detection of Breast Cancer PRINCIPAL INVESTIGATOR: Stephen Johnston CONTRACTING...ADDRESS. 1. REPORT DATE July 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Jul2015 - 30Jun2016 4. TITLE AND SUBTITLE A Simple System for the Early...Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-14-1-0231 Abstract: We invented the immunosignature technology (IMS) as a simple , universal

Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

PubMed Central

2011-01-01

Introduction Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients. Methods We used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available. Results The presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence

NASA's Technology Transfer Program for the Early Detection of Breast Cancer

NASA Technical Reports Server (NTRS)

Schmidt, Gregory; Frey, Mary Anne; Vernikos, Joan; Winfield, Daniel; Dalton, Bonnie P. (Technical Monitor)

1996-01-01

The National Aeronautics and Space Administration (NASA) has led the development of advanced imaging sensors and image processing technologies for space science and Earth science missions. NASA considers the transfer and commercialization of such technologies a fundamental mission of the agency. Over the last two years, efforts have been focused on the application of aerospace imaging and computing to the field of diagnostic imaging, specifically to breast cancer imaging. These technology transfer efforts offer significant promise in helping in the national public health priority of the early detection of breast cancer.

A 'give it a go' breast-feeding culture and early cessation among low-income mothers.

PubMed

Bailey, Cathy; Pain, R H Rachel H; Aarvold, J E Joan E

2004-09-01

to examine cultural expectations and experiences of breast feeding amongst first time mothers from low-income areas, in order to improve understanding of why many cease breast feeding in the early days of their babies' lives. qualitative interviews were carried out with 16 women, who expressed an intention to breast feed, at 37 weeks in their pregnancy and again at 3-9 weeks postnatally. women were interviewed in their own homes in low-income areas of North Tyneside, north-east England. decisions about breast-feeding cessation were usually made within the first few days as women negotiated the pathways of informal cultures of feeding babies and the availability and quality of formal care. A 'give it a go' breast-feeding culture is identified, where women who intended to breast feed had a strong expectation of difficulties and even failure. Expertise and confidence with bottle feeding were more widespread among family and friends. The many influences on the mothers' decision-making were interconnected and contingent upon each other: if one aspect of breast feeding 'goes wrong', other reasons were often brought into play and the underlying pessimism that was felt antenatally was borne out. positive experiences of formal support could make a crucial difference in the early days of breast feeding. However non-breast-feeding cultures permeated and found expression in negative discourses. Support needs to take account of the cultural contexts in which mothers make decisions and the fact that breast feeding is affected by a multitude of factors simultaneously. Access to advice at the right time is a key issue for some low-income women.

Ambient Oxygen Promotes Tumorigenesis

PubMed Central

Starost, Matthew F.; Lago, Cory U.; Lim, Philip K.; Sack, Michael N.; Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M.

2011-01-01

Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53−/− mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53−/− mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo. PMID:21589870

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

PubMed

Neyt, Mattias; Huybrechts, Michel; Hulstaert, Frank; Vrijens, France; Ramaekers, Dirk

2008-08-01

Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

Early Stage Breast Cancer Treatments for Younger Medicare Beneficiaries with Different Disabilities

PubMed Central

Iezzoni, Lisa I; Ngo, Long H; Li, Donglin; Roetzheim, Richard G; Drews, Reed E; McCarthy, Ellen P

2008-01-01

Objective To explore how underlying disability affects treatments and outcomes of disabled women with breast cancer. Data Sources Surveillance, Epidemiology, and End Results program data, linked with Medicare files and Social Security Administration disability group. Study Design Ninety thousand two hundred and forty-three incident cases of early-stage breast cancer under age 65; adjusted relative risks and hazards ratios examined treatments and survival, respectively, for women in four disability groups compared with nondisabled women. Principal Findings Demographic characteristics, treatments, and survival varied among four disability groups. Compared with nondisabled women, those with mental disorders and neurological conditions had significantly lower adjusted rates of breast conserving surgery and radiation therapy. Survival outcomes also varied by disability type. Conclusions Compared with nondisabled women, certain subgroups of women with disabilities are especially likely to experience disparities in care for breast cancer. PMID:18479411

Long non-coding RNA MIAT regulates apoptosis and the apoptotic response to chemotherapeutic agents in breast cancer cell lines.

PubMed

Almnaseer, Z A; Mourtada-Maarabouni, M

2018-06-18

The lncRNA Myocardial Infarction Associated Transcript (MIAT) is involved in a number of diseases, including myocardial infarction and diabetic retinopathy. Emerging evidence suggests that MIAT expression levels are increased in different type of cancers, including breast cancer. In this study we further evaluated the role of MIAT in breast cancer and investigated the consequences of its silencing on breast cancer response to chemotherapeutic agents. Expression levels of MIAT mRNA in breast cancer were determined using TissueScan™ Breast Cancer cDNA Arrays. Breast cancer cell lines were transfected with MIAT specific siRNAs, with silencing confirmed using RT-qPCR and the effects on breast cancer cell survival and response to different apoptotic stimuli determined. MIAT transcript levels were significantly elevated in breast cancer samples. Such increase was specific to the early stages of the disease, ER, PR +ve, HER -ve and TNBC samples. Silencing of MIAT induced growth arrest and increased basal apoptosis. Reduced levels of MIAT augmented the apoptotic response of breast cancer cells to a wide range of apoptotic stimuli. Our results also showed that MIAT down-regulation was associated with a decrease in OCT4 mRNA, suggesting the existence of a MIAT/OCT4 regulatory loop, similar to that observed in malignant mature B cells. Taken together with the recent demonstration of oncogene characteristics, our observations suggest that MIAT plays an important role in breast tumorigenesis. St rategies to decrease MIAT expression levels may improve sensitivity to therapy in breast cancer by enhancing the apoptotic responses to conventional chemotherapies. ©2018 The Author(s).

Checkpoint suppressor 1 suppresses transcriptional activity of ERα and breast cancer cell proliferation via deacetylase SIRT1.

PubMed

Xu, Zhaowei; Yang, Yangyang; Li, Bowen; Li, Yanan; Xia, Kangkai; Yang, Yuxi; Li, Xiahui; Wang, Miao; Li, Shujing; Wu, Huijian

2018-05-11

Breast cancer is a highly heterogeneous carcinoma in women worldwide, but the underlying mechanisms that account for breast cancer initiation and development have not been fully established. Mounting evidence indicates that Checkpoint suppressor 1 (CHES1) is tightly associated with tumorigenesis and prognosis in many types of cancer. However, the definitive function of CHES1 in breast cancer remains to be explored. Here we showed that CHES1 had a physical interaction with estrogen receptor-α (ERα) and repressed the transactivation of ERα in breast cancer cells. Mechanistically, the interaction between CHES1 and ERα enhanced the recruitment of nicotinamide adenine dinucleotide (NAD+) deacetylase Sirtuin 1 (SIRT1), and it further induced SIRT1-mediated ERα deacetylation and repression on the promoter-binding enrichment of ERα. In addition, we also found that the expression of CHES1 was repressed by estrogen-ERα signaling and the expression level of CHES1 was significantly downregulated in ERα-positive breast cancer. The detailed mechanism was that ERα may directly bind to CHES1 potential promoter via recognizing the conserved estrogen response element (ERE) motif in response to estrogen stimulation. Functionally, CHES1 inhibited ERα-mediated proliferation and tumorigenesis of breast cancer cells in vivo and in vitro. Totally, these results identified a negative cross-regulatory loop between ERα and CHES1 that was required for growth of breast cancer cells, it might uncover novel insight into molecular mechanism of CHES1 involved in breast cancer and provide new avenues for molecular-targeted therapy in hormone-regulated breast cancer.

A dyadic approach to understanding the impact of breast cancer on relationships between partners during early survivorship.

PubMed

Keesing, Sharon; Rosenwax, Lorna; McNamara, Beverley

2016-08-25

The shared impact of breast cancer for women and their male partners is emerging as an important consideration during the experience of a breast cancer diagnosis, particularly during survivorship. This study aimed to explore the experiences of women and their partners during early survivorship and contributes a range of insights into the lives of those intimately affected by breast cancer. In-depth interviews were completed with Australian women survivors of breast cancer (n = 8) and their partners (n = 8), between six months and five years following cessation of treatment. Questions included a focus on the women and their partners' daily experiences during early survivorship, including the management of ongoing symptoms, engagement in leisure and social interests, returning to work, communicating with each other, maintenance of the current relationship and other important roles and responsibilities. Thematic analysis was employed to determine key themes arising from the dyadic accounts of women and their partners' experiences during early breast cancer survivorship. Women and their partners experienced many changes to their previous roles, responsibilities and relationships during early breast cancer survivorship. Couples also reported a range of communication, intimacy and sexuality concerns which greatly impacted their interactions with each other, adding further demands on the relationship. Three significant themes were determined: (1) a disconnection within the relationship - this was expressed as the woman survivor of breast cancer needing to prioritise her own needs, sometimes at the expense of her partner and the relationship; (2) reformulating the relationship - this reflects the strategies used by couples to negotiate changes within the relationship; and (3) support is needed to negotiate the future of the relationship - couples emphasised the need for additional support and resources to assist them in maintaining their relationship during early

[Primary safety analysis of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients].

PubMed

Zhou, Ning-Ning; Teng, Xiao-Yu; Liu, Dong-Geng; Xu, Ran; Guan, Zhong-Zhen

2008-12-01

It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis

PubMed Central

Zhang, Jinfang; Wan, Lixin; Dai, Xiangpeng; Sun, Yi; Wei, Wenyi

2014-01-01

The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. APC/C is composed of at least 14 core subunits and recruits its substrates for ubiquitination via one of the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively. Furthermore, recent studies have shed light on crucial functions for APC/C in maintaining genomic integrity, neuronal differentiation, cellular metabolism and tumorigenesis. To gain better insight into the in vivo physiological functions of APC/C in regulating various cellular processes, particularly development and tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or inhibitors have been established and characterized. However, due to their essential role in cell cycle regulation, most of the germline knockout mice targeting the APC/C pathway are embryonic lethal, indicating the need for generating conditional knockout mouse models to assess the role in tumorigenesis for each APC/C signaling component in specific tissues. In this review, we will first provide a brief introduction of the ubiquitin-proteasome system (UPS) and the biochemical activities and cellular functions of the APC/C E3 ligase. We will then focus primarily on characterizing genetic mouse models used to understand the physiological roles of each APC/C signaling component in embryogenesis, cell proliferation, development and carcinogenesis. Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets. PMID:24569229

Diet, Stem Cells, and Breast Cancer Prevention

DTIC Science & Technology

2011-01-01

pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN, daidzein) from legumes and red...Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167–81. [41...38], capsaicin from chili pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN

Characterization of potential driver mutations involved in human breast cancer by computational approaches

PubMed Central

Rajendran, Barani Kumar; Deng, Chu-Xia

2017-01-01

Breast cancer is the second most frequently occurring form of cancer and is also the second most lethal cancer in women worldwide. A genetic mutation is one of the key factors that alter multiple cellular regulatory pathways and drive breast cancer initiation and progression yet nature of these cancer drivers remains elusive. In this article, we have reviewed various computational perspectives and algorithms for exploring breast cancer driver mutation genes. Using both frequency based and mutational exclusivity based approaches, we identified 195 driver genes and shortlisted 63 of them as candidate drivers for breast cancer using various computational approaches. Finally, we conducted network and pathway analysis to explore their functions in breast tumorigenesis including tumor initiation, progression, and metastasis. PMID:28477017

[Early detection of breast and cervical cancer among indigenous communities in Morelos, Mexico].

PubMed

Campero, Lourdes; Atienzo, Erika E; Marín, Eréndira; de la Vara-Salazar, Elvia; Pelcastre-Villafuerte, Blanca; González, Guillermo

2014-01-01

To analyze the perception in relation to when and how to perform actions for the early detection of breast and cervical cancer among women and health care providers in communities with a high percentage of indigenous population in Morelos, Mexico. Ten health providers and 58 women users of health services were interviewed which have a first level of attention in five communities. The analysis was developed under the approach of the Grounded Theory. Providers are poorly informed about current regulations and specific clinical indications for the detection of cervical and breast cancer. Few practice health literacy under intercultural sensitization. The users have imprecise or wrong notions of the early detection. The need for training in adherence to norms is evident. It is urgent to assume a culturally relevant approach to enable efficient communication and promote health literacy for early detection of these two cancers.

Early termination of breast-feeding in periurban Santo Domingo, Dominican Republic: mothers' community perceptions and personal practices.

PubMed

McLennan, J D

2001-06-01

The objectives of this study were to determine: 1) whether mothers' perceptions of typical community practice for breast-feeding duration influence their personal practices and 2) whether the mothers' reports of community reasons for terminating breast-feeding identify barriers not elicited through self-report. The study was conducted in 1997 in a sample of poor neighborhoods in a periurban district of Santo Domingo, the capital of the Dominican Republic. A representative sample of 220 mothers from these neighborhoods was interviewed with a structured questionnaire. While the duration of breast-feeding was similar for self-report and for mothers' perceptions of typical community practice, there was no statistically significant correlation between these two variables. "Mother-driven" reasons for early termination of breast-feeding, such as "fear of loss of figure or of breast shape" and "not wanting to breast-feed," were frequently perceived as community reasons but rarely given as personal reasons. Personal reasons were predominately "child-driven," including "the child not wanting the breast," or reasons beyond the mother's control such as having "insufficient" milk. Maternal report of community reasons for early termination may be a useful way to identify factors that would not otherwise be revealed on self-report. These additional reasons may guide health promotion efforts aimed at increasing breast-feeding duration.

Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan.

PubMed

Rashid, Muhammad U; Muhammad, Noor; Amin, Asim; Loya, Asif; Hamann, Ute

2017-01-01

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers. Pakistan has one of the highest rates of breast cancer incidence in Asia, where BRCA1/2 small-range mutations account for 17% of early-onset and familial breast/ovarian cancer patients. We report the first study from Pakistan evaluating the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in breast and/or ovarian cancer patients who do not harbor small-range BRCA1/2 mutations. Both BRCA1/2 genes were comprehensively screened for LGRs using multiplex ligation-dependent probe amplification in 120 BRCA1/2 small-range mutations negative early-onset or familial breast/ovarian cancer patients from Pakistan (Group 1). The breakpoints were characterized by long-range PCR- and DNA-sequencing analyses. An additional cohort of 445 BRCA1/2 negative high-risk patients (Group 2) was analyzed for the presence of LGRs identified in Group 1. Three different BRCA1 LGRs were identified in Group 1 (4/120; 3.3%), two of these were novel. Exon 1-2 deletion was observed in two unrelated patients: an early-onset breast cancer patient and another bilateral breast cancer patient from a hereditary breast cancer (HBC) family. Novel exon 20-21 deletion was detected in a 29-year-old breast cancer patient from a HBC family. Another novel exon 21-24 deletion was identified in a breast-ovarian cancer patient from a hereditary breast and ovarian cancer family. The breakpoints of all deletions were characterized. Screening of the 445 patients in Group 2 for the three LGRs revealed ten additional patients harboring exon 1-2 deletion or exon 21-24 deletion (10/445; 2.2%). No BRCA2 LGRs were identified. LGRs in BRCA1 are found with a considerable frequency in Pakistani breast/ovarian cancer cases. Our findings suggest that BRCA1 exons 1-2 deletion and exons 21-24 deletion should be included in the recurrent BRCA1/2 mutations panel for genetic testing of high-risk Pakistani

Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

PubMed

Bychkovsky, Brittany L; Lin, Nancy U

2017-02-01

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Barriers to early presentation of breast cancer among women in Soweto, South Africa

PubMed Central

McCormack, Valerie Ann; Das, Ishani; Neugut, Alfred I.; Jacobson, Judith S.

2018-01-01

Purpose Reported breast cancer incidence is rising in South Africa, where some women are diagnosed late and have poor outcomes. We studied patient and provider factors associated with clinical stage at diagnosis among women diagnosed at the Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg in 2015–2016. Methods From face-to-face interviewer-administered questionnaires we compared self-reported socioeconomics, demographics, comorbidities, risk factors, personal and health system barriers, and from patient clinical records, clinical staging, receptor subtype, and tumor grade among 499 consecutive women newly diagnosed with advanced stage (III/IV) breast cancer versus those diagnosed early (stage 0/I/II). Logistic regression models were used to identify factors associated with advanced stage at diagnosis. Results Among the women, 243 (49%) were diagnosed at early and 256 (51%) at advanced stages. In the multiple logistic regression adjusted model, completion of high school or beyond (odds ratio (OR) 0.59, and greater breast cancer knowledge and awareness (OR 0.86) were associated with lower stage of breast cancer at presentation. Advanced stage was associated with Luminal B (OR 2.25) and triple-negative subtypes (OR 3.17) compared to luminal A, with delays >3 months from first breast symptoms to accessing the health system (OR 2.79) and with having more than 1 visit within the referral health system (OR 3.19) for 2 visits; OR 2.73 for ≥3 visits). Conclusions Limited patient education, breast cancer knowledge and awareness, and health system inefficiencies were associated with advanced stage at diagnosis. Sustained community and healthcare worker education may down-stage disease and improve cancer outcomes. PMID:29394271

Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers

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

Pignol, Jean-Philippe, E-mail: j.p.pignol@erasmusmc.nl; Radiation Oncology Department, Erasmus Medical Center Cancer Institute, Rotterdam; Caudrelier, Jean-Michel

Purpose: Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of {sup 103}Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials. Methods and Materials: The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm{sup 3}. The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t testsmore » for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms. Results: The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years. Conclusions: The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.« less

Implementation of the National Breast and Cervical Cancer Early Detection Program

PubMed Central

Lee, Nancy C.; Wong, Faye L.; Jamison, Patricia M.; Jones, Sandra F.; Galaska, Louise; Brady, Kevin T.; Wethers, Barbara; Stokes-Townsend, George-Ann

2015-01-01

In 1990, Congress passed the Breast and Cervical Cancer Mortality Prevention Act because of increases in the number of low-income and uninsured women being diagnosed with breast cancer. This act authorized the Centers for Disease Control and Prevention (CDC) to establish the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to provide high-quality and timely breast and cervical cancer screening and diagnostic services to low-income, uninsured women. The program started in 1991, and, in 1993, Congress amended the act to allow the CDC to fund American Indian and Alaska Native tribes and tribal organizations. By 1996, the program was providing cancer screening across the United States. To ensure appropriate delivery and monitoring of services, the program adopted detailed policies on program management, evidence-based guidelines for clinical services, a systematized clinical data system to track service quality, and key partnerships that expand the program’s reach. The NBCCEDP currently funds 67 programs, including all 50 states, the District of Columbia, 5 US territories, and 11 tribes or tribal organizations. PMID:25099896

Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

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

Bergom, Carmen; Kelly, Tracy; Bedi, Meena

Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with themore » BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m{sup 2}; 91% of the patients were overweight (BMI ≥25 kg/m{sup 2}) and 69% of the patients were clinically obese (BMI ≥30 kg/m{sup 2}). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m{sup 2} (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated

Breast cancer in the 21st century: from early detection to new therapies.

PubMed

Merino Bonilla, J A; Torres Tabanera, M; Ros Mendoza, L H

The analysis of the causes that have given rise to a change in tendency in the incidence and mortality rates of breast cancer in the last few decades generates important revelations regarding the role of breast screening, the regular application of adjuvant therapies and the change of risk factors. The benefits of early detection have been accompanied by certain adverse effects, even in terms of an excessive number of prophylactic mastectomies. Recently, several updates have been published on the recommendations in breast cancer screening at an international level. On the other hand, the advances in genomics have made it possible to establish a new molecular classification of breast cancer. Our aim is to present an updated overview of the epidemiological situation of breast cancer, as well as some relevant issues from the point of view of diagnosis, such as molecular classification and different strategies for both population-based and opportunistic screening. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

The Human Cell Surfaceome of Breast Tumors

PubMed Central

da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

2013-01-01

Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants

PubMed Central

Moyon, Thomas; Antignac, Jean-Philippe; Qannari, El Mostafa; Croyal, Mikaël; Soumah, Mohamed; David-Sochard, Agnès; Billard, Hélène; Legrand, Arnaud; Boscher, Cécile; Darmaun, Dominique; Rozé, Jean-Christophe

2018-01-01

Human milk is recommended for feeding preterm infants. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth-pattern of preterm infants fed their own mother’s milk. A prospective-monocentric-observational birth-cohort was established, enrolling 138 preterm infants, who received their own mother’s breast-milk throughout hospital stay. All infants were ranked according to the change in weight Z-score between birth and hospital discharge. Then, we selected infants who experienced “slower” (n = 15, −1.54 ± 0.42 Z-score) or “faster” (n = 11, −0.48 ± 0.19 Z-score) growth; as expected, although groups did not differ regarding gestational age, birth weight Z-score was lower in the “faster-growth” group (0.56 ± 0.72 vs. −1.59 ± 0.96). Liquid chromatography–mass spectrometry lipidomic signatures combined with multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between groups. Validation of the selected biomarkers was performed using multidimensional statistical, false-discovery-rate and ROC (Receiver Operating Characteristic) tools. Breast-milk associated with faster growth contained more medium-chain saturated fatty acid and sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. The ability of such biomarkers to predict early-growth was validated in presence of confounding clinical factors but remains to be ascertained in larger cohort studies. PMID:29385065

Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

2005-01-01

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study

PubMed Central

Chen, Wendy Y; Michels, Karin B; Cho, Eunyoung; Willett, Walter C; Eliassen, A Heather

2016-01-01

Objective To evaluate the association between fruit and vegetable intake during adolescence and early adulthood and risk of breast cancer. Design Prospective cohort study. Setting Health professionals in the United States. Participants 90 476 premenopausal women aged 27-44 from the Nurses’ Health Study II who completed a questionnaire on diet in 1991 as well as 44 223 of those women who completed a questionnaire about their diet during adolescence in 1998. Main outcome measure Incident cases of invasive breast cancer, identified through self report and confirmed by pathology report. Results There were 3235 cases of invasive breast cancer during follow-up to 2013. Of these, 1347 cases were among women who completed a questionnaire about their diet during adolescence (ages 13-18). Total fruit consumption during adolescence was associated with a lower risk of breast cancer. The hazard ratio was 0.75 (95% confidence interval 0.62 to 0.90; P=0.01 for trend) for the highest (median intake 2.9 servings/day) versus the lowest (median intake 0.5 serving/day) fifth of intake. The association for fruit intake during adolescence was independent of adult fruit intake. There was no association between risk and total fruit intake in early adulthood and total vegetable intake in either adolescence or early adulthood. Higher early adulthood intake of fruits and vegetables rich in α carotene was associated with lower risk of premenopausal breast cancer. The hazard ratio was 0.82 (0.70 to 0.96) for the highest fifth (median intake 0.5 serving/day) versus the lowest fifth (median intake 0.03 serving/day) intake. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor negative cancers than estrogen and progesterone receptor positive cancers (P=0.02 for heterogeneity). For individual fruits and vegetables, greater consumption of apple, banana, and grapes during adolescence and oranges and kale during early adulthood was

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

PubMed

Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

2018-01-21

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

Referral, Receipt, and Completion of Chemotherapy in Patients With Early-Stage Breast Cancer Older Than 65 Years and at High Risk of Breast Cancer Recurrence

PubMed Central

Buist, Diana S.M.; Chubak, Jessica; Prout, Marianne; Yood, Marianne Ulcickas; Bosco, Jaclyn L.F.; Thwin, Soe Soe; Gold, Heather Taffet; Owusu, Cynthia; Field, Terry S.; Quinn, Virginia P.; Wei, Feifei; Silliman, Rebecca A.

2009-01-01

Purpose Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. Patients and Methods A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). Results Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. Conclusion Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence. PMID:19687341

Cosmetic Analysis Following Breast-Conserving Surgery and Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer: A Prospective Clinical Study

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

Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd

Purpose: To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. Methods and Materials: Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a causemore » for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. Results: Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. Conclusions: Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA.« less

Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis

PubMed Central

Ortiz, Berenice; White, Julie R.; Wu, Wei H.; Chan, Timothy A.

2014-01-01

PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently inactivated across many human cancers. Despite its frequent inactivation, it is unknown whether loss of PTPRD promotes tumorigenesis in vivo. PTPRD is located on chromosome 9p, as is CDKN2A, and the two loci are frequently deleted together. Here, we show that co-deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis. Interestingly, heterozygous loss of Ptprd was sufficient to promote tumorigenesis in our model, suggesting that Ptprd may be a haploinsufficient tumor suppressor. The loss of Ptprd resulted in changes to the tumor spectrum in mice and increased the frequency of lymphomas. In total, we reveal that Ptprd is a tumor suppressor that can promote tumorigenesis in concert with Cdkn2a loss. PMID:25138050

[Prognostic factors of early breast cancer].

PubMed

Almagro, Elena; González, Cynthia S; Espinosa, Enrique

2016-02-19

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

LncRNA EGOT Promotes Tumorigenesis Via Hedgehog Pathway in Gastric Cancer.

PubMed

Peng, Wei; Wu, Jianzhong; Fan, Hong; Lu, Jianwei; Feng, Jifeng

2017-12-05

Gastric cancer (GC) is one of the mostly terminal malignancies with poor prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the breast cancer. However, the function of EGOT in GC remains unknown. This work was to explore the clinical value and biological significance of EGOT in GC. EGOT levels in GC tissue and cell were analyzed by qRT-PCR. After knockdown of EGOT, GC cell growth and cycle progression were detected. The expression of EGOT was observably elevated in GC. Upregulation of EGOT was related with lymphatic metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could significantly inhibit GC cell proliferation and arrest cycle progression in G1 phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog signaling pathway in GC cells. EGOT functions as an oncogene in GC, and may be useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.

Recent advances on the stimulatory effects of metals in breast cancer.

PubMed

Lappano, Rosamaria; Malaguarnera, Roberta; Belfiore, Antonino; Maggiolini, Marcello

2017-12-05

Certain environmental chemicals may accumulate in human serum and tissues eliciting estrogenic and/or carcinogenic effects. Therefore, there is heightened interest in determining whether environmental chemicals may increase the risk for endocrine-related tumors like breast cancer. For instance, metals as cadmium, zinc, copper, iron, nickel and aluminum have been shown to mimic estrogen action. Moreover, the exposure to these chemicals has been reported to stimulate diverse malignancies including breast cancer, which is the most common tumor in women worldwide. In this review, we summarize the epidemiologic and experimental evidence regarding the association between the exposure to some trace elements and breast cancer risk. We also address recent insights on the molecular mechanisms involved by metals in breast tumorigenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

WE-FG-207A-01: Introduction to Dedicated Breast CT - Early Studies

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

Vedantham, S.

Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detectionmore » more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

PubMed

Schäfer, Rebekka; Strnad, Vratislav; Polgár, Csaba; Uter, Wolfgang; Hildebrandt, Guido; Ott, Oliver J; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Lyczek, Jaroslaw; Guinot, Jose Luis; Dunst, Jürgen; Miguelez, Cristina Gutierrez; Slampa, Pavel; Allgäuer, Michael; Lössl, Kristina; Kovács, György; Fischedick, Arnt-René; Fietkau, Rainer; Resch, Alexandra; Kulik, Anna; Arribas, Leo; Niehoff, Peter; Guedea, Ferran; Schlamann, Annika; Gall, Christine; Polat, Bülent

2018-04-20

Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at

Lactate dehydrogenase downregulation mediates the inhibitory effect of diallyl trisulfide on proliferation, metastasis, and invasion in triple-negative breast cancer.

PubMed

Cheng, Shi-Yann; Yang, Yao-Chih; Ting, Kuan-Lun; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang; Kuo, Wei-Wen

2017-04-01

The Warburg effect plays a critical role in tumorigenesis, suggesting that specific agents targeting Warburg effect key proteins may be a promising strategy for cancer therapy. Previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of breast cancer cells by inducing apoptosis in vitro and in vivo. However, whether the Warburg effect is involved with the apoptosis-promoting action of DATS is unclear. Here, we show that the action of DATS is associated with downregulation of lactate dehydrogenase A (LDHA), an essential protein of the Warburg effect whose upregulation is closely related to tumorigenesis. Interestingly, inhibition of the Warburg effect by DATS in breast cancer cells did not greatly affect normal cells. Furthermore, DATS inhibited growth of breast cancer cells, particularly in MDA-MB-231, a triple-negative breast cancer (TNBC) cell, and reduced proliferation and migration; invasion was reversed by over-expression of LDHA. These data suggest that DATS inhibits breast cancer growth and aggressiveness through a novel pathway targeting the key enzyme of the Warburg effect. Our study shows that LDHA downregulation is involved in the apoptotic effect of DATS on TNBC. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1390-1398, 2017. © 2016 Wiley Periodicals, Inc.

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

NASA Astrophysics Data System (ADS)

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

Breast Cancer Knowledge, Behaviors, and Preferences in Malawi: Implications for Early Detection Interventions From a Discrete Choice Experiment.

PubMed

Kohler, Racquel E; Gopal, Satish; Lee, Clara N; Weiner, Bryan J; Reeve, Bryce B; Wheeler, Stephanie B

2017-10-01

Breast cancer is the most common female cancer in Africa and leading cause of death resulting from cancer; however, many countries lack early detection services. In Malawi, women are frequently diagnosed with large tumors after long symptomatic periods. Little is known about local cancer knowledge. We administered a cross-sectional survey with a discrete choice experiment to a random sample in urban and rural areas of Lilongwe district. Bivariable and multivariable analyses determined factors associated with knowledge. Preference utilities for early detection interventions were estimated using a hierarchical Bayesian model in Sawtooth software. Of 213 women recruited, fewer than half were aware of breast cancer. In multivariable analysis, electricity at home and knowing someone with cancer increased the odds of awareness. Women were more knowledgeable about symptoms than treatment or risk factors; more than 60% erroneously believed local misconceptions. Seventeen percent were aware of breast self-examination, and 20% were aware of clinical breast examination (CBE); few reported either behavior. Common barriers included not knowing where to access CBE and transportation difficulties. Discrete choice experiment results indicated the detection strategy (breast health awareness, CBE, or both) was the most important attribute of an intervention, followed by the encounter setting and travel time. Addressing misconceptions in health messages and engaging survivors to promote early detection may help improve breast cancer knowledge in Malawi. Program designs accounting for women's preferences should provide breast health education and CBEs in convenient settings to address transportation barriers, particularly for women with low socioeconomic position.

Breast Cancer Knowledge, Behaviors, and Preferences in Malawi: Implications for Early Detection Interventions From a Discrete Choice Experiment

PubMed Central

Gopal, Satish; Lee, Clara N.; Weiner, Bryan J.; Reeve, Bryce B.; Wheeler, Stephanie B.

2017-01-01

Purpose Breast cancer is the most common female cancer in Africa and leading cause of death resulting from cancer; however, many countries lack early detection services. In Malawi, women are frequently diagnosed with large tumors after long symptomatic periods. Little is known about local cancer knowledge. Methods We administered a cross-sectional survey with a discrete choice experiment to a random sample in urban and rural areas of Lilongwe district. Bivariable and multivariable analyses determined factors associated with knowledge. Preference utilities for early detection interventions were estimated using a hierarchical Bayesian model in Sawtooth software. Results Of 213 women recruited, fewer than half were aware of breast cancer. In multivariable analysis, electricity at home and knowing someone with cancer increased the odds of awareness. Women were more knowledgeable about symptoms than treatment or risk factors; more than 60% erroneously believed local misconceptions. Seventeen percent were aware of breast self-examination, and 20% were aware of clinical breast examination (CBE); few reported either behavior. Common barriers included not knowing where to access CBE and transportation difficulties. Discrete choice experiment results indicated the detection strategy (breast health awareness, CBE, or both) was the most important attribute of an intervention, followed by the encounter setting and travel time. Conclusion Addressing misconceptions in health messages and engaging survivors to promote early detection may help improve breast cancer knowledge in Malawi. Program designs accounting for women’s preferences should provide breast health education and CBEs in convenient settings to address transportation barriers, particularly for women with low socioeconomic position. PMID:29094086

Five-year Results of Whole Breast Intensity Modulated Radiation Therapy for the Treatment of Early Stage Breast Cancer: The Fox Chase Cancer Center Experience

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

Keller, Lanea M.M., E-mail: Lanea.Keller@fccc.edu; Sopka, Dennis M.; Li Tianyu

Purpose: To report the 5-year outcomes using whole-breast intensity-modulated radiation therapy (IMRT) for the treatment of early-stage-breast cancer at the Fox Chase Cancer Center. Methods and Materials: A total of 946 women with early-stage breast cancer (stage 0, I, or II) were treated with IMRT after surgery with or without systemic therapy from 2003-2010. Whole-breast radiation was delivered via an IMRT technique with a median whole-breast radiation dose of 46 Gy and median tumor bed boost of 14 Gy. Endpoints included local-regional recurrence, cosmesis, and late complications. Results: With a median follow-up of 31 months (range, 1-97 months), there weremore » 12 ipsilateral breast tumor recurrences (IBTR) and one locoregional recurrence. The 5-year actuarial IBTR and locoregional recurrence rates were 2.0% and 2.4%. Physician-reported cosmestic outcomes were available for 645 patients: 63% were considered 'excellent', 33% 'good', and <1.5% 'fair/poor'. For physician-reported cosmesis, boost doses {>=}16 Gy, breast size >900 cc, or boost volumes >34 cc were significantly associated with a 'fair/poor' cosmetic outcome. Fibrosis, edema, erythema, and telangectasia were also associated with 'fair/poor' physician-reported cosmesis; erythema and telangectasia remained significant on multivariate analysis. Patient-reported cosmesis was available for 548 patients, and 33%, 50%, and 17% of patients reported 'excellent', 'good', and 'fair/poor' cosmesis, respectively. The use of a boost and increased boost volume: breast volume ratio were significantly associated with 'fair/poor' outcomes. No parameter for patient-reported cosmesis was significant on multivariate analysis. The chances of experiencing a treatment related effect was significantly associated with a boost dose {>=}16 Gy, receipt of chemotherapy and endocrine therapy, large breast size, and electron boost energy. Conclusions: Whole-breast IMRT is associated with very low rates of local recurrence at 5

Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

PubMed

Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

2017-05-01

Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2 + /ErbB2 + ) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2 + /ErbB2 + breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2 + /ErbB2 + breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

77 FR 71193 - Breast and Cervical Cancer Early Detection Federal Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Breast and Cervical Cancer Early Detection Federal Advisory Committee Correction: This notice was published in the Federal Register on November 5, 2012, Volume 77, Number 214, Page 66469. A teleconference line...

Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue.

PubMed

Muenst, Simone; Mechera, Robert; Däster, Silvio; Piscuoglio, Salvatore; Ng, Charlotte K Y; Meier-Abt, Fabienne; Weber, Walter P; Soysal, Savas D

2017-04-04

Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven't been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans. We collected benign breast tissue of 125 women who had been stratified according to age at first pregnancy and the occurrence of subsequent breast cancer, and performed immunohistochemistry for PR, Wnt4 and the Wnt-target Versican. The number of PR positive epithelial cells was significantly lower in the group of women with early pregnancy and no subsequent breast cancer compared to the group of nulliparous women with subsequent invasive breast cancer (p = 0.0135). In women with early pregnancy, expression of Versican and Wnt4 was significantly lower compared to nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican expression was also significant lower compared to women with late pregnancy (p < 0.0001). Our results confirm prior observations in mice and suggest a role of downregulation of epithelial Wnt signaling in the protective effect of early pregnancy in humans. This results in a decreased proliferation of stem/progenitor cells; therefore, the Wnt signaling pathway may represent a potential target for breast cancer prevention in humans.

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. ...

Sentinel Lymph Node Biopsy in Early Breast Cancer.

PubMed

Kühn, Thorsten

2011-01-01

The role of axillary surgery for the treatment of primary breast cancer is in a process of constant change. During the last decade, axillary dissection with removal of at least 10 lymph nodes (ALD) was replaced by sentinel lymph node biopsy (SLNB) as a staging procedure. Since then, the indication for SLNB rapidly expanded. Today's surgical strategies aim to minimize the rate of patients with a negative axillary status who undergo ALD. For some subgroups of patients, the indication for SLNB (e.g. multicentric disease, large tumors) or its implication for treatment planning (micrometastatic involvement, neoadjuvant chemotherapy) is being discussed. Although the indication for ALD is almost entirely restricted to patients with positive axillary lymph nodes today, the therapeutic effect of completion ALD is more and more questioned. On the other hand, the diagnostic value of ALD in node-positive patients is discussed. This article reflects today's standards in axillary surgery and discusses open issues on the diagnostic and therapeutic role of SLNB and ALD in the treatment of early breast cancer.

Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women.

PubMed

Obeidat, Rana F

2015-01-01

To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers' support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system.

iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

PubMed

Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

2015-10-01

To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

Early European experience with the MammoSite radiation therapy system for partial breast brachytherapy following breast conservation operation in low-risk breast cancer.

PubMed

Niehoff, Peter; Ballardini, B; Polgár, C; Major, T; Hammer, J; Richetti, A; Kovács, G

2006-06-01

Preliminary results of ultrasound studies do exist in the literature on the successful use of the MammoSite Radiation Therapy System (RTS), a new device for delivering brachytherapy following breast-conserving surgery. In Europe, some groups started a prospective multicentre trial to investigate the use of the MammoSite RTS. In this early publication, we analysed the surgical procedure and placement of the MammoSite, treatment planning and radiation delivery complications, and early cosmesis, as well as the comfort of the patients. Between June 2002 and March 2005, a total of 54 low-risk breast cancer patients fulfilling the enrolment criteria were implanted intra- or postoperatively using the MammoSite applicator. After inflating the balloon in the excision cavity, the reference isodose was defined 1cm from the balloon's surface. Twenty-eight patients were treated with primary brachytherapy with a total dose of 34 Gy (2x3.4 Gy) and 16 patients had a boost with a mean dose of 13.3 Gy (range: 7.5-15 Gy; 2x2.5 Gy) combined with external beam radiotherapy (EBRT). Doses ranged between 46 and 50 Gy. We analysed the postimplant anatomic position of the applicator in relation to the skin and chest wall as well as the geometric form of the balloon via ultrasound, computed tomography and X-ray before, during and after the treatment. Forty-four out of 54 patients (81.5%) were eligible for MammoSite RTS brachytherapy. Ten patients were excluded from the trial due to the strict study criteria and received no brachytherapy. Balloon rupture occurred in two cases. We observed seroma in 16 patients (36%); furthermore, an abscess developed in two patients (4.5%) within 3 months of implantation. Postoperative air gaps and haematoma were successfully reduced by draining the operation cavity in one institution. At a mean follow-up of 14 months (range 3-31 months), the skin-related side effects observed were skin discoloration or inflammation in 36 patients (82%) and teleangiectasia in

The preventive effect of breast-feeding for longer than 6 months on early pubertal development among children aged 7-9 years in Korea.

PubMed

Lee, Hye Ah; Kim, Young Ju; Lee, Hwayoung; Gwak, Hye Sun; Hong, Young Sun; Kim, Hae Soon; Park, Eun Ae; Cho, Su Jin; Ha, Eun Hee; Park, Hyesook

2015-12-01

The present study was performed to investigate whether breast-feeding is associated with early pubertal development among children 7-9 years old in Korea. Children were divided into those who did and did not receive breast-feeding for 6 months or longer in accordance with the recommendations of the WHO. Pubertal status was determined by clinical examination using Tanner staging. Prospective observational study. We conducted a follow-up study of children aged 7-9 years in 2011 who had taken part in the Ewha Birth & Growth Cohort study. Fifty (22.8%) of the total of 219 children were in early puberty, with the proportion being slightly higher for girls (24.1%) than boys (21.4%). Children who had entered early puberty were taller, weighed more and had a higher concentration of insulin-like growth factor 1. Moreover, the change in weight Z-score from birth to follow-up was significantly lower in children who were breast-fed than in those who were not (weight Z-score change: 0.32 (sd 1.59) v. 0.77 (sd 1.61), respectively, P=0.04). Comparison of breast-feeding by puberty status indicated a preventive association with early puberty in children who were breast-fed for 6 months or longer (OR=0.37; 95% CI 0.18, 0.74). This association remained significant after adjustment for relevant covariates. These results demonstrate a beneficial association between breast-feeding and early pubertal development, especially in those breast-fed for 6 months or longer. The study suggests that interventions would need to start early in life to prevent early pubertal development.

The Hippo signaling pathway in liver regeneration and tumorigenesis.

PubMed

Hong, Lixin; Cai, Yabo; Jiang, Mingting; Zhou, Dawang; Chen, Lanfen

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved signaling module that plays critical roles in liver size control and tumorigenesis. The Hippo pathway consists of a core kinase cascade in which the mammalian Ste20-like kinases (Mst1/2, orthologs of Drosophila Hippo) and their cofactor Salvador (Sav1) form a complex to phosphorylate and activate the large tumor suppressor (Lats1/2). Lats1/2 kinases in turn phosphorylate and inhibit the transcription co-activators, the Yes-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ), two major downstream effectors of the Hippo pathway. Losses of the Hippo pathway components induce aberrant hepatomegaly and tumorigenesis, in which YAP coordinates regulation of cell proliferation and apoptosis and plays an essential role. This review summarizes the current findings of the regulation of Hippo signaling in liver regeneration and tumorigenesis, focusing on how the loss of tumor suppressor components of the Hippo pathway results in liver cancers and discussing the molecular mechanisms that regulate the expression and activation of its downstream effector YAP in liver tumorigenesis. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Glyceollins as novel targeted therapeutic for the treatment of metastatic triple-negative breast cancer

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA MB 231 cells. Triple negative (ER , PgR, and Her2/neu ...

Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

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

Moran, Meena S., E-mail: meena.moran@yale.edu; Yang Qifeng; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, People's Republic of China

2011-12-01

Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpressionmore » of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study.

PubMed

Farvid, Maryam S; Chen, Wendy Y; Michels, Karin B; Cho, Eunyoung; Willett, Walter C; Eliassen, A Heather

2016-05-11

To evaluate the association between fruit and vegetable intake during adolescence and early adulthood and risk of breast cancer. Prospective cohort study. Health professionals in the United States. 90 476 premenopausal women aged 27-44 from the Nurses' Health Study II who completed a questionnaire on diet in 1991 as well as 44 223 of those women who completed a questionnaire about their diet during adolescence in 1998. Incident cases of invasive breast cancer, identified through self report and confirmed by pathology report. There were 3235 cases of invasive breast cancer during follow-up to 2013. Of these, 1347 cases were among women who completed a questionnaire about their diet during adolescence (ages 13-18). Total fruit consumption during adolescence was associated with a lower risk of breast cancer. The hazard ratio was 0.75 (95% confidence interval 0.62 to 0.90; P=0.01 for trend) for the highest (median intake 2.9 servings/day) versus the lowest (median intake 0.5 serving/day) fifth of intake. The association for fruit intake during adolescence was independent of adult fruit intake. There was no association between risk and total fruit intake in early adulthood and total vegetable intake in either adolescence or early adulthood. Higher early adulthood intake of fruits and vegetables rich in α carotene was associated with lower risk of premenopausal breast cancer. The hazard ratio was 0.82 (0.70 to 0.96) for the highest fifth (median intake 0.5 serving/day) versus the lowest fifth (median intake 0.03 serving/day) intake. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor negative cancers than estrogen and progesterone receptor positive cancers (P=0.02 for heterogeneity). For individual fruits and vegetables, greater consumption of apple, banana, and grapes during adolescence and oranges and kale during early adulthood was significantly associated with a reduced risk of breast cancer. Fruit juice intake

Somatic mutations in early onset luminal breast cancer

PubMed Central

de Lyra, Eduardo Carneiro; Hirata Katayama, Maria Lucia; Maistro, Simone; de Vasconcellos Valle, Pedro Wilson Mompean; de Lima Pereira, Gláucia Fernanda; Rodrigues, Lívia Munhoz; de Menezes Pacheco Serio, Pedro Adolpho; de Gouvêa, Ana Carolina Ribeiro Chaves; Geyer, Felipe Correa; Basso, Ricardo Alves; Pasini, Fátima Solange; del Pilar Esteves Diz, Maria; Brentani, Maria Mitzi; Guedes Sampaio Góes, João Carlos; Chammas, Roger; Boutros, Paul C.; Koike Folgueira, Maria Aparecida Azevedo

2018-01-01

Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. PMID:29854292

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

PubMed

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Stories about breast cancer in Australian women's magazines: information sources for risk, early detection and treatment.

PubMed

Wilkes, L; Withnall, J; Harris, R; White, K; Beale, B; Hobson, J; Durham, M; Kristjanson, L

2001-06-01

Sixty articles in five Australian women's magazines were analyzed for journalistic qualities, metaphors, narrative features and accuracy of clinical facts related to risk, early detection and treatment of breast cancer. The stories were features, news features or soft news stories. The stories reflected the 'good news' editorial style of women's magazines. A dominant theme in the stories was that early detection of breast cancer is crucial and equals survival. While there were few inaccuracies in the stories, there was little detail of treatment modalities, an emphasis on lifestyle as a risk factor and a prevailing message that a genetic history of breast cancer means you will get it. A major implication of the findings is that nurses, who provide information to women, must be aware of the goals of journalists and the educational power of narrative logic of stories in women's magazines.

Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis.

PubMed

Chen, Yong; Wang, Lijuan; Xu, Hexiang; Liu, Xingxiang; Zhao, Yingren

2013-10-01

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third primary cause of cancer-related mortality worldwide. The molecular mechanisms underlying the initiation and formation of HCC remain obscure. In the present study, we performed exome sequencing using tumor and normal tissues from 3 hepatitis B virus (HBV)-positive BCLC stage A HCC patients. Bioinformatic analysis was performed to find candidate protein-altering somatic mutations. Eighty damaging mutations were validated and 59 genes were reported to be mutated in HBV-related HCCs for the first time here. Further analysis using whole genome sequencing (WGS) data of 88 HBV-related HCC patients from the European Genome-phenome Archive database showed that mutations in 33 of the 59 genes were also detected in other samples. Variants of two newly found genes, ZNF717 and PARP4, were detected in more than 10% of the WGS samples. Several other genes, such as FLNA and CNTN2, are also noteworthy. Thus, the exome sequencing analysis of three BCLC stage A patients provides new insights into the molecular events governing the early steps of HBV-induced HCC tumorigenesis.

Geographic proximity to treatment for early stage breast cancer and likelihood of mastectomy.

PubMed

Boscoe, Francis P; Johnson, Christopher J; Henry, Kevin A; Goldberg, Daniel W; Shahabi, Kaveh; Elkin, Elena B; Ballas, Leslie K; Cockburn, Myles

2011-08-01

Women with early stage breast cancer who live far from a radiation therapy facility may be more likely to opt for mastectomy over breast conserving surgery (BCS). The geographic dimensions of this relationship deserve further scrutiny. For over 100,000 breast cancer patients in 10 states who received either mastectomy or BCS, a newly-developed software tool was used to calculate the shortest travel distance to the location of surgery and to the nearest radiation treatment center. The likelihood of receipt of mastectomy was modeled as a function of these distance measures and other demographic variables using multilevel logistic regression. Women traveling over 75 km for treatment are about 1.4 times more likely to receive a mastectomy than those traveling under 15 km. Geographic barriers to optimal breast cancer treatment remain a valid concern, though most women traveling long distances to receive mastectomies are doing so after bypassing local options. Copyright © 2011 Elsevier Ltd. All rights reserved.

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure.

PubMed

Ramchand, Sabashini K; Seeman, Ego; Wang, Xiao-Fang; Ghasem-Zadeh, Ali; Francis, Prudence A; Ponnusamy, Evangeline J; Bardin, Michele S; Bui, Minh; Zebaze, Roger; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

In premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6-120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. Compared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. The severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Estrogen receptor-β in mitochondria: implications for mitochondrial bioenergetics and tumorigenesis.

PubMed

Liao, Tien-Ling; Tzeng, Chii-Ruey; Yu, Chao-Lan; Wang, Yi-Pei; Kao, Shu-Huei

2015-09-01

Estrogen enhances mitochondrial function by enhancing mitochondrial biogenesis and sustaining mitochondrial energy-transducing capacity. Shifts in mitochondrial bioenergetic pathways from oxidative phosphorylation to glycolysis have been hypothesized to be involved in estrogen-induced tumorigenesis. Studies have shown that mitochondria are an important target of estrogen. Estrogen receptor-β (ERβ) has been shown to localize to mitochondria in a ligand-dependent or -independent manner and can affect mitochondrial bioenergetics and anti-apoptotic signaling. However, the functional role of mitochondrial ERβ in tumorigenesis remains unclear. Clinical studies of ERβ-related tumorigenesis have shown that ERβ stimulates mitochondrial metabolism to meet the high energy demands of processes such as cell proliferation, cell survival, and transformation. Thus, in elucidating the precise role of mitochondrial ERβ in cell transformation and tumorigenesis, it will be particularly valuable to explore new approaches for the development of medical treatments targeting mitochondrial ERβ-mediated mitochondrial function and preventing apoptosis. © 2015 New York Academy of Sciences.

Psychosocially influenced cancer: diverse early-life stress experiences and links to breast cancer.

PubMed

Schuler, Linda A; Auger, Anthony P

2010-11-01

This perspective on Boyd et al. (beginning on page 1398 in this issue of the journal) discusses recent published research examining the interplay between social stress and breast cancer. Cross-disciplinary studies using genetically defined mouse models and established neonatal and peripubertal paradigms of social stress are illuminating biological programming by diverse early-life experiences for the risk of breast cancer. Understanding the mechanisms underlying this programming can lead to the identification of risk factors and sensitive developmental windows, enabling improved prevention and treatment strategies for this devastating disease. ©2010 AACR.

Estrogen regulates Hippo signaling via GPER in breast cancer

PubMed Central

Zhou, Xin; Wang, Shuyang; Wang, Zhen; Feng, Xu; Liu, Peng; Lv, Xian-Bo; Li, Fulong; Yu, Fa-Xing; Sun, Yiping; Yuan, Haixin; Zhu, Hongguang; Xiong, Yue; Lei, Qun-Ying; Guan, Kun-Liang

2015-01-01

The G protein–coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis. PMID:25893606

Estrogen regulates Hippo signaling via GPER in breast cancer.

PubMed

Zhou, Xin; Wang, Shuyang; Wang, Zhen; Feng, Xu; Liu, Peng; Lv, Xian-Bo; Li, Fulong; Yu, Fa-Xing; Sun, Yiping; Yuan, Haixin; Zhu, Hongguang; Xiong, Yue; Lei, Qun-Ying; Guan, Kun-Liang

2015-05-01

The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.

Breast and cervical cancers diagnosed and stage at diagnosis among women served through the National Breast and Cervical Cancer Early Detection Program.

PubMed

Miller, Jacqueline W; Royalty, Janet; Henley, Jane; White, Arica; Richardson, Lisa C

2015-05-01

To assess cancers diagnosed and the stage of cancer at the time of diagnosis among low-income, under-insured, or uninsured women who received services through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Using the NBCCEDP database, we examined the number and percent of women diagnosed during 2009-2011 with in situ breast cancer, invasive breast cancer, and invasive cervical cancer by demographic and clinical characteristics, including age, race and ethnicity, test indication (screening or diagnostic), symptoms (for breast cancer), and screening history (for cervical cancer). We examined these characteristics by stage at diagnosis, a new variable included in the database obtained by linking with state-based central cancer registries. There were 11,569 women diagnosed with invasive breast cancer, 1,988 with in situ breast cancer, and 583 with invasive cervical cancer through the NBCCEDP. Women who reported breast symptoms or who had diagnostic mammography were more likely to be diagnosed with breast cancer, and at a later stage, than those who did not have symptoms or who had screening mammography. Women who had been rarely or never screened for cervical cancer were more likely to be diagnosed with cervical cancer, and at a later stage, than women who received regular screenings. Women served through the NBCCEDP who have not had prior screening or who have symptoms were more often diagnosed with late-stage disease.

Arab American women's lived experience with early-stage breast cancer diagnosis and surgical treatment.

PubMed

Obeidat, Rana Fakhri; Lally, Robin M; Dickerson, Suzanne S

2012-01-01

Currently, limited literature addresses Arab American women's responses to the impact of breast cancer and its treatments. The objective of the study was to understand the experience of being diagnosed with and undergoing surgical treatment for early-stage breast cancer among Arab American women. A qualitative interpretive phenomenological research design was used for this study. A purposive sample of 10 Arab American women who were surgically treated for early-stage breast cancer in the United States was recruited. Data were collected using individual interviews and analyzed using the Heideggerian hermeneutical methodology. Arab American women accepted breast cancer diagnosis as something in God's hands that they had no control over. Although they were content with God's will, the women believed that the diagnosis was a challenge that they should confront. The women confronted this challenge by accessing the healthcare system for treatment, putting trust in their physicians, participating when able in treatment decisions, using religious practices for coping, maintaining a positive attitude toward the diagnosis and the treatment, and seeking information. Arab American women's fatalistic beliefs did not prevent them from seeking care and desiring treatment information and options when diagnosed with breast cancer. It is important that healthcare providers encourage patients to express meanings they attribute to their illness to provide them with appropriate supportive interventions. They should also individually assess patients' decision-making preferences, invite them to participate in decision making, and provide them with tailored means necessary for such participation without making any assumptions based on patients' ethnic/cultural background.

Biological Characteristics and Genetic Heterogeneity between Carcinoma-Associated Fibroblasts and Their Paired Normal Fibroblasts in Human Breast Cancer

PubMed Central

Hou, Yixuan; Sun, Yan; Wang, Liyang; Luo, Haojun; Peng, Huimin; Liu, Manran

2013-01-01

Background The extensional signals in cross-talk between stromal cells and tumor cells generated from extracellular matrix molecules, soluble factor, and cell-cell adhesion complexes cooperate at the extra- and intracellular level in the tumor microenvironment. CAFs are the primary type of stromal cells in the tumor microenvironment and play a pivotal role in tumorigenesis and development. Hitherto, there is hardly any systematic analysis of the intrinsic relationship between CAFs function and its abnormal signaling pathway. The extreme complexity of CAFs’ features and their role in tumor development are needed to be further investigated. Methodology/Principal Findings We primary cultured CAFs and NFs from early stages of breast cancer tissue and identified them using their biomarker by immunohistochemistry for Fibronectin, α-SMA and FAP. Microarray was applied to analyze gene expression profiles of human breast CAFs and the paired NFs. The Up-regulated genes classified by Gene Ontology, signal pathways enriched by DAVID pathway analysis. Abnormal signaling pathways in breast cancer CAFs are involved in cell cycle, cell adhesion, signal transduction and protein transport being reported in CAFs derived from other tumors. Significantly, the altered ATM signaling pathway, a set of cell cycle regulated signaling, and immune associated signaling are identified to be changed in CAFs. Conclusions/Significance CAFs have the vigorous ability of proliferation and potential of invasion and migration comparing with NFs. CAFs could promote breast cancer cell invasion under co-culture conditions through up-regulated CCL18 and CXCL12. Consistently with its biologic behavior, the gene expression profiling analyzed by microarray shows that some of key signaling pathways, such as cell cycle, cell adhesion, and secreting factors play an important role in CAFs. The altered ATM signaling pathway is abnormally active in the early stage of breast cancer. The set of immune associated

Tamoxifen enhances therapeutic effects of gemcitabine on cholangiocarcinoma tumorigenesis.

PubMed

Jing, Gu; Yuan, Kaiyu; Turk, Amy N; Jhala, Nirag C; Arnoletti, Juan P; Zhang, Kui; McDonald, Jay M; Chen, Yabing

2011-06-01

Cholangiocarcinoma is a highly malignant tumor with limited therapeutic options. We have previously reported that tamoxifen (TMX) induces apoptosis of cholangiocarcinoma cells and reduces cholangiocarcinoma tumorigenesis in mice. In the present studies, we determined the effect of combination therapy of TMX and gemcitabine (GMT), another chemotherapeutical reagent for many cancers, on cholangiocarcinoma tumorigenesis and investigated the responsible mechanisms. GMT inhibited cell growth and induced apoptosis of cholangiocarcinoma cells in a concentration-dependent manner. TMX enhanced GMT-induced apoptosis of cholangiocarcinoma cells. Consistently, GMT (15 mg/kg) inhibited cholangiocarcinoma tumorigenesis in nude mice by 50%. TMX (15 mg/kg) enhanced the inhibitory effect of GMT on tumorigenesis by 33%. The inhibition of tumor growth correlated with enhanced apoptosis in tumor tissues. To elucidate the mechanisms underlying the additive effects of TMX on GMT-induced apoptosis, we determined the activation of caspases in cholangiocarcinoma cells exposed to GMT, TMX, or both. Activation of caspases 9 and 3, as well as cytochrome c release to the cytosol, was demonstrated in cells exposed to both reagents. In contrast, TMX activated caspase 2, whereas GMT had no effect. Inhibition of caspase 2 activation decreased TMX-, but not GMT-, induced activation of caspase 3 and apoptosis of cholangiocarcinoma cells. Similarly, activation of caspase 2 was found in tumors from TMX-treated mice, but not GMT-treated mice. Therefore, the enhanced effect of TMX on GMT-induced cholangiocarcinoma cell death is partially mediated by activation of caspase 2. TMX and GMT both induce apoptosis and inhibit cholangiocarcinoma tumorigenesis, which may be attributed to the activation of distinct apoptosis signals by TMX and GMT. Our studies provide in vivo evidence and molecular insight to support the use of TMX and GMT in combination as an effective therapy for cholangiocarcinoma.

Early Breast Cancer Diagnosis Using Microwave Imaging via Space-Frequency Algorithm

NASA Astrophysics Data System (ADS)

Vemulapalli, Spandana

The conventional breast cancer detection methods have limitations ranging from ionizing radiations, low specificity to high cost. These limitations make way for a suitable alternative called Microwave Imaging, as a screening technique in the detection of breast cancer. The discernible differences between the benign, malignant and healthy breast tissues and the ability to overcome the harmful effects of ionizing radiations make microwave imaging, a feasible breast cancer detection technique. Earlier studies have shown the variation of electrical properties of healthy and malignant tissues as a function of frequency and hence stimulates high bandwidth requirement. A Ultrawideband, Wideband and Narrowband arrays have been designed, simulated and optimized for high (44%), medium (33%) and low (7%) bandwidths respectively, using the EM (electromagnetic software) called FEKO. These arrays are then used to illuminate the breast model (phantom) and the received backscattered signals are obtained in the near field for each case. The Microwave Imaging via Space-Time (MIST) beamforming algorithm in the frequency domain, is next applied to these near field backscattered monostatic frequency response signals for the image reconstruction of the breast model. The main purpose of this investigation is to access the impact of bandwidth and implement a novel imaging technique for use in the early detection of breast cancer. Earlier studies show the implementation of the MIST imaging algorithm on the time domain signals via a frequency domain beamformer. The performance evaluation of the imaging algorithm on the frequency response signals has been carried out in the frequency domain. The energy profile of the breast in the spatial domain is created via the frequency domain Parseval's theorem. The beamformer weights calculated using these the MIST algorithm (not including the effect of the skin) has been calculated for Ultrawideband, Wideband and Narrowband arrays, respectively

Breast feeding and early adolescent behaviour, self-esteem and depression: Hong Kong's 'Children of 1997' birth cohort.

PubMed

Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

2013-11-01

Breast feeding may contribute to neurological development and hence mental health. However, associations from Western populations are unclear, and most likely confounded by socioeconomic position (SEP), making evidence from other sociocultural settings valuable. We examined whether breast feeding was associated with early adolescent emotional and behavioural problems, self-esteem and depressive symptoms in a non-Western developed setting, where socioeconomic patterning of breast feeding differs from but other postnatal characteristics are similar to Western settings. The adjusted associations of breast feeding with emotional and behavioural problems assessed from parent-reported Rutter z-score at ~11 years (n=5598, 67% follow-up), self-reported self-esteem z-score at ~11 years (n=6937, 84%) and depressive symptoms assessed from self-reported Patient Health Questionnaire-9 z-score at ~13 years (n=5797, 70%) were examined using multivariable linear regression in a population-representative Hong Kong Chinese birth cohort, 'Children of 1997'. Mothers from families with higher education tended to start but not sustain breast feeding, whereas migrant mothers tended to start and sustain breast feeding. Breast feeding for 3+ months had mostly null associations with Rutter score, self-esteem or depressive symptoms adjusted for sex, age, survey mode, SEP, parents' age, birth weight-for-gestational age, birth order and secondhand smoke exposure, although partial breast feeding for any length of time or exclusive breast feeding for <3 months was associated with poorer behaviour (higher Rutter z-score (0.10, 95% CI 0.05 to 0.16)) and lower self-esteem (-0.09, 95% CI -0.14 to -0.04). In a non-Western developed setting, breast feeding was inconsistently associated with several early adolescent mental health measures suggesting a reflection of setting specific unmeasured confounding.

Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis.

PubMed

Wu, Lisha; Jiang, Hong; Chawsheen, Hedy A; Mishra, Murli; Young, Matthew R; Gerard, Matthieu; Toledano, Michel B; Colburn, Nancy H; Wei, Qiou

2014-05-01

Sulfiredoxin (Srx), the exclusive enzyme that reduces the hyperoxidized inactive form of peroxiredoxins (Prxs), has been found highly expressed in several types of human skin cancer. To determine whether Srx contributed to skin tumorigenesis in vivo, Srx null mice were generated on an FVB background. Mouse skin tumorigenesis was induced by a 7,12-dimethylbenz[α]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) protocol. We found that the number, volume and size of papillomas in Srx(-/-) mice were significantly fewer compared with either wild-type (Wt) or heterozygous (Het) siblings. Histopathological analysis revealed more apoptotic cells in tumors from Srx(-/-) mice. Mechanistic studies in cell culture revealed that Srx was stimulated by TPA in a redox-independent manner. This effect was mediated transcriptionally through the activation of mitogen-activated protein kinase and Jun-N-terminal kinase. We also demonstrated that Srx was capable of reducing hyperoxidized Prxs to facilitate cell survival under oxidative stress conditions. These findings suggested that loss of Srx protected mice, at least partially, from DMBA/TPA-induced skin tumorigenesis. Therefore, Srx has an oncogenic role in skin tumorigenesis and targeting Srx may provide novel strategies for skin cancer prevention or treatment.

Barriers to early presentation and diagnosis of breast cancer among African women living in sub-Saharan Africa

PubMed Central

Akuoko, Cynthia Pomaa; Armah, Ernestina; Sarpong, Theresa; Quansah, Dan Yedu; Amankwaa, Isaac

2017-01-01

Background Breast cancer (BC) has been described as the leading cause of cancer deaths among women especially in the developing world including sub Saharan Africa (SSA). Delayed presentation and late diagnosis at health facilities are parts of the contributing factors of high BC mortality in Africa. This review aimed to appraise the contributing factors to delayed breast cancer presentation and diagnosis among SSA women. Methods Five databases encompassing medical and social sciences were systematically searched using predefined search terms linked with breast cancer presentation and diagnosis and sub Saharan Africa. Reference lists of relevant papers were also hand searched. Quality of quantitative and qualitative articles were assessed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and the Critical Appraisal Skills Programme (CASP) quality appraisal checklist. Thematic analysis was used to synthesize the qualitative studies to integrate findings. Results Fourteen (14) quantitative studies, two (2) qualitative studies and one (1) mixed method study merited inclusion for analysis. This review identified low knowledge of breast cancer among SSA women. This review also found lack of awareness of early detection treatment, poor perception of BC, socio-cultural factors such as belief, traditions and fear as factors impacting African women’s health seeking behavior in relation to breast cancer. Conclusion Improving African women’s knowledge and understanding will improve behaviors related to breast cancer and facilitate early presentation and detection and enhance proper management and treatment of breast cancer. PMID:28192444

Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan.

PubMed

Rashid, Muhammad U; Muhammad, Noor; Faisal, Saima; Amin, Asim; Hamann, Ute

2013-06-27

Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage. In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2). Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women.

National program of breast cancer early detection in Brod-Posavina County (East Croatia).

PubMed

Jurišić, Irena; Kolovrat, Ana; Mitrečić, Drago; Cvitković, Ante

2014-09-01

Results of the National Program of Breast Cancer Early Detection in Brod-Posavina County during the 2006-2012 period are presented. Response rate in two National Program cycles, cancers detected according to factors such as first and last menstruation, age at cancer detection, deliveries and mammography findings according to the Breast Imaging Reporting and Data System (BI-RADS) before diagnosis verification were analyzed. Data were obtained from the software connecting Public Health Institutes via Ministry of Health server and questionnaires filled out by the women presenting for screening and processed by the method of descriptive statistics. Mammography findings were classified according to the BI-RADS classification. In two National Program cycles during the 2006-2012 period, women aged 50-69 were called for mammography screening. In the first cycle, the response rate in Brod-Posavina County was 53.2%, with 71 cancers detected at a mean age of 61.3 years. In the second cycle, the response rate was 57.0%, with 44 cancers detected at a mean age of 62.5 years. In the first and second cycles, there were 21.1% and 14.3% of mammography findings requiring additional work-up (BI-RADS 0), respectively. Particular risk factors such as early menarche, late menopause, parity, positive family history and presence of benign breast lesions were not demonstrated in women with verified cancer. There was no increase in the incidence of breast cancer per 100,000 inhabitants in the Brod-Posavina County following implementation of the National Program. In conclusion, efforts should be focused on increasing public health awareness, ensuring appropriate professional staff engaged in screening, and improving medical care in order to reduce the time elapsed from establishing suspicion to confirming the diagnosis of breast cancer.

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

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

Chan, Elisa K.; Woods, Ryan; McBride, Mary L.

Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiacmore » risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early

Targeting Premalignant Lesions - Implications for Early Breast Cancer Detection and Intervention

DTIC Science & Technology

2017-04-01

lesions. Peptide conjugated AgNP were injected intravenously in mice and mammary glands were isolated and analyzed for nanoparticle accumulation by silver ...Furthermore, these probes will be used to develop targeted therapeutic nanoparticles for early intervention in breast cancer. 2. KEYWORDS...cancer (Months 18-24) (To be done) Specific Aim 3: Target premalignant lesions utilizing peptide-conjugated nanoparticles to prevent/delay

Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women

PubMed Central

Obeidat, Rana F.

2015-01-01

To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers’ support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system. PMID:27981122

Symptomatic hypoglycemia causing brain injury in a term breast fed newborn following early discharge.

PubMed

Marwah, Ashish; Gathwala, Geeta

2011-12-01

Cerebral metabolism and functioning depends upon an adequate blood glucose supply which provides for majority of the brain's energy requirement. Studies from the past have shown that neonatal hypoglycemia is associated with acute and long term neurological sequelae. Early discharge without adequately established breast feeding may lead to feeding problems, post discharge hypoglycemia and its associated neurological complications. The authors describe one such case of an exclusively breast fed term newborn who presented on day 3 with symptomatic hypoglycemia and associated neurological injury.

Duration of breast feeding and arterial distensibility in early adult life: population based study.

PubMed

Leeson, C P; Kattenhorn, M; Deanfield, J E; Lucas, A

2001-03-17

To test the hypothesis that duration of breast feeding is related to changes in vascular function relevant to the development of cardiovascular disease. Population based observational study. Cambridge. 331 adults (171 women, 160 men) aged between 20 and 28 years, born in Cambridge Maternity Hospital. Distensibility of brachial artery, type and duration of infant feeding, current lipid profile, and other cardiovascular risk factors. The longer the period of breast feeding the less distensible the artery wall in early adult life, with no sex differences (regression coefficient = -3.93 micrometer/month, 95% confidence interval -7.29 to -0.57, P=0.02). However, in those breast fed for less than four months, arterial distensibility was not significantly reduced compared with an exclusively formula fed group. The vascular changes observed were not explained by alterations in plasma cholesterol concentration in adult life. Breast feeding in infancy is related to reduced arterial function 20 years later. These data should not alter current recommendations in favour of breast feeding, which has several benefits for infant health. Further work is needed, however, to explore the optimal duration of breast feeding in relation to cardiovascular outcomes.

Anthracycline Use for Early Stage Breast Cancer in the Modern Era: a Review.

PubMed

Jasra, Sakshi; Anampa, Jesus

2018-05-11

Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20-30%. Anthracycline toxicities include the rare-but potential morbid-cardiotoxicity or leukemogenic effect, and the almost universal-but very distressing-alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer. Current literature supports that anthracyclines are not required for all patients with breast cancer and should be avoided in those with high cardiac risk. Recent results from the ABC trials suggest that anthracyclines should not be spared for patients with triple negative breast cancer (regardless of axillary node involvement) or HER2-/ER+ with significant node involvement. Based on current literature, for HER2-negative patients with low-risk breast cancer, anthracyclines could be spared with regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF) or docetaxel and cyclophosphamide (TC). Patients with intermediate or high-risk breast cancer should be considered for anthracycline-based regimens based on other factors such as age, comorbidities, tumor grade, lymphovascular invasion, and genomic profiling. Patients with HER2-positive breast cancer with low risk could be treated with paclitaxel and trastuzumab. For the remaining patients with HER2 overexpression, while docetaxel, carboplatin, and trastuzumab (TCH) has demonstrated to improve disease-free survival (DFS), anthracycline-containing regimens should be discussed, especially for those with very high-risk breast cancer. Although several biomarkers, such as topoisomerase II (TOP2A) and chromosome 17 centromeric duplication (Ch17CEP) have been proposed to predict benefit from

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.

Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography in Patients with Early-stage Breast Cancer.

PubMed

Tuohinen, Suvi Sirkku; Keski-Pukkila, Konsta; Skyttä, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka; Nikus, Kjell

2018-04-01

Early electrocardiogram (ECG) changes after breast cancer radiotherapy (RT) have been reported, but their characteristics and associated factors are largely unknown. This study aimed to explore early RT-induced ECG changes and to compare them with echocardiography changes. Sixty eligible patients with chemotherapy-naïve left-sided and 20 with right-sided breast cancer were evaluated with echocardiography, blood samples and ECG before and after RT. RT-induced ECG changes in the anterior leads. T-Wave changes were most frequent. T-Wave decline was associated independently with patient age (β=-0.245, p=0.005), mean heart radiation dose (β=1.252, p=0.001) and global systolic strain rate change (β=7.943, p=0.002). T-Wave inversion was associated independently with mean heart radiation dose (β=0.143, p<0.001), global longitudinal strain change (β=0.053, p=0.017) and posterior calibrated integrated backscatter (β=-0.022, p=0.049). RT-induced ECG changes were prevalent and associated with functional and structural changes in echocardiography. ECG could be used for post-RT cardiac screening. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

PubMed Central

Schuur, Eric; Angel Aristizabal, Javier; Bargallo Rocha, Juan Enrique; Cabello, Cesar; Elizalde, Roberto; García‐Estévez, Laura; Gomez, Henry L.; Katz, Artur; Nuñez De Pierro, Aníbal

2017-01-01

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision‐making. This review details the development and validation of six multi‐gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use. PMID:28211064

Nanoparticles target early-stage breast cancer metastasis in vivo

NASA Astrophysics Data System (ADS)

Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

2017-10-01

Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

An in vivo study of Cdh1/APC in breast cancer formation

PubMed Central

Fujita, Takeo; Liu, Weijun; Doihara, Hiroyoshi; Wan, Yong

2017-01-01

Dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in several types of tumorigenesis. Our previous studies have shown the potential role of Cdh1/APC in regulating tumor formation via governing the Skp2-p27-cyclinE/CDK2 axis. In this work, we utilized a xenograft mouse breast cancer model to identify the mechanism by which Cdh1/APC potentially suppresses tumor growth in vivo. Here, we report that depletion of Cdh1 results in a significant enhancement of the breast tumor proliferation, while elevated Cdh1 leads to suppression of breast tumor growth. Analysis of breast tissue arrays has indicated that higher levels of Cdh1 are associated with normal breast epithelial tissues whereas lower Skp2 expression and elevated p27 levels are detected. Conversely, the percentage of breast cancer tissues stained positive for Cdh1 and p27 are significantly lower with higher Skp2 levels. Thus, the E3 ligase, Cdh1/APC, may inhibit breast tumor growth via regulating Skp2-p27 mediated cell cycle progression. PMID:19350629

Cognitive and Social Processes Predicting Partner Psychological Adaptation to Early Stage Breast Cancer

PubMed Central

Manne, Sharon; Ostroff, Jamie; Fox, Kevin; Grana, Generosa; Winkel, Gary

2009-01-01

Introduction The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners’ psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning-making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined. Materials and Methods Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner’s diagnosis (n= 253), nine (n = 167), and 18 months (n = 149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning-making, and general and cancer-specific distress at all time points. Results Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer-specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer-specific distress were found. Conclusions Results indicate several cognitive-social processes directly predict partner distress. However, moderator effect models in which the effects of partners’ processing depends upon whether these efforts result changes in perceptions of the cancer experience may add to the understanding of partners’ adaptation to cancer. PMID:18435865

Cognitive and social processes predicting partner psychological adaptation to early stage breast cancer.

PubMed

Manne, Sharon; Ostroff, Jamie; Fox, Kevin; Grana, Generosa; Winkel, Gary

2009-02-01

The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners' psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined. Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner's diagnosis (N=253), 9 (N=167), and 18 months (N=149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning making, and general and cancer-specific distress at all time points. Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer-specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer-specific distress were found. Results indicate several cognitive-social processes directly predict partner distress. However, moderator effect models in which the effects of partners' processing depends upon whether these efforts result in changes in perceptions of the cancer experience may add to the understanding of partners' adaptation to cancer.

Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

PubMed Central

Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

2012-01-01

Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target. PMID:22341523

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

PubMed

O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

2018-03-01

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

PubMed Central

Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

2015-01-01

Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

Review of Factors Influencing Women's Choice of Mastectomy Versus Breast Conserving Therapy in Early Stage Breast Cancer: A Systematic Review.

PubMed

Gu, Jeffrey; Groot, Gary; Boden, Catherine; Busch, Angela; Holtslander, Lorraine; Lim, Hyun

2018-01-03

We have performed a narrative synthesis. A literature search was conducted between January 2000 and June 2014 in 7 databases. The initial search identified 2717 articles; 319 underwent abstract screening, 67 underwent full-text screening, and 25 final articles were included. This review looked at early stage breast cancer in women only, excluding ductal carcinoma in situ and advanced breast cancer. A conceptual framework was created to organize the central constructs underlying women's choices: clinicopathologic factors, physician factors, and individual factors with subgroups of sociodemographic, geographic, and personal beliefs and preferences. This framework guided our review's synthesis and analysis. We found that larger tumor size and increasing stage was associated with increased rates of mastectomy. The results for age varied, but suggested that old and young extremes of diagnostic age were associated with an increased likelihood of mastectomy. Higher socioeconomic status was associated with higher breast conservation therapy (BCT) rates. Resident rural location and increasing distance from radiation treatment facilities were associated with lower rates of BCT. Individual belief factors influencing women's choice of mastectomy (mastectomy being reassuring, avoiding radiation, an expedient treatment) differed from factors influencing choice of BCT (body image and femininity, physician recommendation, survival equivalence, less surgery). Surgeon factors, including female gender, higher case numbers, and individual surgeon practice, were associated with increased BCT rates. The decision-making process for women with early stage breast cancer is complicated and affected by multiple factors. Organizing these factors into central constructs of clinicopathologic, individual, and physician factors may aid health-care professionals to better understand this process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Prospective Longitudinal Clinical Trial Evaluating Quality of Life After Breast-Conserving Surgery and High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer

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

Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd A.

2013-12-01

Purpose: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, versionmore » 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.« less

Epigenetics of breast cancer: modifying role of environmental and bioactive food compounds

PubMed Central

Romagnolo, Donato F.; Daniels, Kevin D.; Grunwald, Jonathan T.; Ramos, Stephan A.; Propper, Catherine R.; Selmin, Ornella I.

2017-01-01

Scope Reduced expression of tumor suppressor genes (TSG) increases the susceptibility to breast cancer. However, only a small percentage of breast tumors is related to family history and mutational inactivation of TSG. Epigenetics refers to non-mutational events that alter gene expression. Endocrine disruptors found in foods and drinking water may disrupt epigenetically hormonal regulation and increase breast cancer risk. This review centers on the working hypothesis that agonists of the aromatic hydrocarbon receptor (AHR); bisphenol A (BPA); and arsenic compounds, induce in TSG epigenetic signatures that mirror those often seen in sporadic breast tumors. Conversely, it is hypothesized that bioactive food components that target epigenetic mechanisms protect against sporadic breast cancer induced by these disruptors. Methods and results This review highlights 1) overlaps between epigenetic signatures placed in TSG by AHR-ligands, BPA, and arsenic with epigenetic alterations associated with sporadic breast tumorigenesis; and 2) potential opportunities for prevention of sporadic breast cancer with food components that target the epigenetic machinery. Conclusions Characterizing the overlap between epigenetic signatures elicited in TSG by endocrine disruptors with those observed in sporadic breast tumors may afford new strategies for breast cancer prevention with specific bioactive food components or diet. PMID:27144894

Survival is Better After Breast Conserving Therapy than Mastectomy for Early Stage Breast Cancer: A Registry-Based Follow-up Study of Norwegian Women Primary Operated Between 1998 and 2008.

PubMed

Hartmann-Johnsen, Olaf Johan; Kåresen, Rolf; Schlichting, Ellen; Nygård, Jan F

2015-11-01

Breast-conserving therapy (BCT) and mastectomy (MTX) has been considered to have a similar long-time survival. However, better survival in women undergoing BCT compared with MTX is found in two recent register studies from the United States. The purpose of this study was to compare survival after BCT and MTX for women with early-stage breast cancer in Norway. Women with invasive, early-stage breast cancer (1998-2008) where BCT and MTX were considered as equally beneficial treatments were included for a total of 13,015 women. Surgery was divided in two main cohorts (primary BCT, primary MTX) and five subcohorts. Analyses were stratified into T1N0M0, T2N0M0, T1N1M0, T2N1M0, and age groups (<50, 50-69, ≥70). Overall survival and breast cancer-specific survival (BCSS) were calculated in life tables, hazard ratios by Cox regression, and sensitivity analyses. Five-year BCSS for women who underwent primary BCT or primary MTX was 97 and 88 %, respectively. Women who underwent primary MTX had a hazard ratio of 1.64 (95 % confidence interval 1.43-1.88) for breast cancer death compared with women who underwent primary BCT after adjusting for the year of diagnosis, age at diagnosis, stage, histology, and grade. Survival was better or equal after breast-conserving therapy than mastectomy in all early stages, surgical subcohorts, and age groups. This advantage could not only be attributed to differences in tumor biology.

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

PubMed

Basaran, Gul; Turhal, Nazım Serdar; Cabuk, Devrim; Yurt, Nevin; Yurtseven, Gul; Gumus, Mahmut; Teomete, Mehmet; Dane, Faysal; Yumuk, Perran Fulden

2011-06-01

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases

Quality of breast cancer early detection services conducted by well woman clinics in the district of Gampaha, Sri Lanka.

PubMed

Vithana, Palatiyana Vithanage Sajeewanie Chiranthika; Ariyaratne, May; Jayawardana, Pl

2013-01-01

Breast cancer is the most common cancer diagnosed in females in Sri Lanka and early detection can lead to reduction in morbidity and mortality. To evaluate selected aspects of breast cancer early detection services implemented through well woman clinics (WWCs) in the Gampaha District. The study consisted of two components. A retrospective descriptive arm assessed clinical breast examination (CBE) coverage of target age group women (TGW) of 35-59 years in all the WWCs in Gampaha district over 2003- 2007. A cross sectional descriptive study additionally assessed quality of breast cancer early detection services. The Lot Quality Assurance Sampling (LQAS) technique was used to decide on the lot size and threshold values, which were computed as twenty and six clinics. Checklists were employed in assessing coverage, physical facilities and clinic activities. Client satisfaction on WWC services was assessed among 200 TGW attending 20 WWCs using an interviewer-administered questionnaire. CBE coverage in the Gampaha district increased only from 1.1-2.2% over 2003-2007. With regard to physical facilities, the number of clinics that were rated substandard varied between 7-18 (35- 90%). The items that were lacking included dust bins, notice boards, stationary, furniture and linen, and cleanliness of outside premises and toilets. With regard to clinic activities, punctuality of staff, late commencement of clinics, provision of health education, supervision, CBE and breast self-examination (BSE) were substandard in 7- 20 clinics (35-100%). Client satisfaction for WWC services was 45.2% (IQR: 38.7-54.8%) and only 11% had a score of ≥70%, the cut off set for satisfaction. Breast cancer early detection service coverage in the Gampaha district remained low (2.2%) in 2007, 11 years after commencing WWCs. All 20 clinics were substandard for overall CBE and BSE.

Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-γ

PubMed Central

Lee, Hong Jin; Ju, Jihyeung; Paul, Shiby; So, Jae-Young; DeCastro, Andrew; Smolarek, Amanda; Lee, Mao-Jung; Yang, Chung S.; Newmark, Harold L.; Suh, Nanjoo

2009-01-01

Purpose Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of α-tocopherol (vitamin E) have been studied for decades, recent intervention studies with α-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of 4 isoforms, α, β, γ, and δ variants, and recent attention is being made to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in γ- and δ-tocopherols against mammary tumorigenesis. Experimental Design Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in γ- and δ-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. Results Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3 and peroxisome proliferator activated receptor-γ (PPAR-γ), and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that γ- and δ-tocopherols, but not α-tocopherol, activated PPAR-γ and antagonized estrogen action in breast cancer. Conclusion The results suggest that γ- and δ-tocopherols may be effective agents for the prevention of breast cancer. PMID:19509159

Breast Cancer Stage, Surgery, and Survival Statistics for Idaho’s National Breast and Cervical Cancer Early Detection Program Population, 2004–2012

PubMed Central

Graff, Robert; Moran, Patti; Cariou, Charlene; Bordeaux, Susan

2015-01-01

Introduction The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides access to breast and cervical cancer screening for low-income, uninsured, and underinsured women in all states and US territories. In Idaho, a rural state with very low breast and cervical cancer screening rates, this program is called Women’s Health Check (WHC). The program has been operating continuously since 1997 and served 4,719 enrollees in 2013. The objective of this study was to assess whether disparities existed in cause-specific survival (a net survival measure representing survival of a specified cause of death in the absence of other causes of death) between women screened by WHC and outside WHC and to determine how type of surgery or survival varies with stage at diagnosis. Methods WHC data were linked to Idaho’s central cancer registry to compare stage distribution, type of surgery, and cause-specific survival between women with WHC-linked breast cancer and a comparison group of women whose records did not link to the WHC database (nonlinked breast cancer). Results WHC-linked breast cancer was significantly more likely to be diagnosed at a later stage of disease than nonlinked breast cancer. Because of differences in stage distribution between WHC-linked and nonlinked breast cancers, overall age-standardized, cause-specific breast cancer survival proportions diverged over time, with a 5.1 percentage-point deficit in survival among WHC-linked cases at 5 years of follow-up (83.9% vs 89.0%). Differences in type of surgery and cause-specific survival were attenuated when controlling for stage. Conclusion This study suggests that disparities may exist for Idaho WHC enrollees in the timely diagnosis of breast cancer. To our knowledge, this is the first study to publish comparisons of cause-specific breast cancer survival between NBCCEDP-linked and nonlinked cases. PMID:25789497

Effect of marination on color lightness of early-deboned broiler breast fillets varies with raw meat color attributes

USDA-ARS?s Scientific Manuscript database

ABSTRACT The effect of vacuum-tumbling marination on meat color and pH was evaluated in early-deboned chicken breast fillets with different color attributes or color lightness. Broiler breast fillets deboned at 2 h postmortem (PM) were collected from a commercial processing plant based on visual c...

A Critical Reassessment of the Role of Mitochondria in Tumorigenesis

PubMed Central

Salas, Antonio; Yao, Yong-Gang; Macaulay, Vincent; Vega, Ana; Carracedo, Ángel; Bandelt, Hans-Jürgen

2005-01-01

Background Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. Methods and Findings In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. Conclusion The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research. PMID:16187796

Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan

PubMed Central

2013-01-01

Background Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage. Methods In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. Results Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2). Conclusion Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women. PMID:23806170

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

PubMed Central

Acharya, Sunil; Xu, Jia; Wang, Xiao; Jain, Shalini; Wang, Hai; Zhang, Qingling; Chang, Chia-Chi; Bower, Joseph; Arun, Banu; Seewaldt, Victoria; Yu, Dihua

2016-01-01

Tamoxifen and aromatase inhibitors (AIs) have shown efficacy in prevention of estrogen receptor-positive (ER+) breast cancer; however, there exists no proven prevention strategy for estrogen receptor-negative (ER-) breast cancer. Up to 40% of ER- breast cancers have human epidermal growth factor receptor 2 overexpression (HER2+), suggesting HER2 signaling might be a good target for chemoprevention for certain ER- breast cancers. Here, we tested the feasibility of the HER2-targeting agent lapatinib in prevention and/or early intervention of an ER-/HER2+ early-stage breast disease model. We found that lapatinib treatment forestalled the progression of atypical ductal hyperplasia (ADH)-like acini to ductal carcinoma in situ (DCIS)-like acini in ER-/HER2+ human mammary epithelial cells (HMECs) in 3D culture. Mechanistically, we found that inhibition of HER2/Akt signaling by lapatinib led to downregulation of GLUT4 and a reduced glucose uptake in HER2-overexpressing cells, resulting in decreased proliferation and increased apoptosis of these cells in 3D culture. Additionally, our data suggest that HER2-driven glycolytic metabolic dysregulation in ER-/HER2+ HMECs might promote early-stage breast disease progression, which can be reversed by lapatinib treatment. Furthermore, low-dose lapatinib treatment, starting at the early stages of mammary grand transformation in the MMTV-neu* mouse model, significantly delayed mammary tumor initiation and progression, extended tumor-free survival, which corresponded to effective inhibition of HER2/Akt signaling and downregulation of GLUT4 in vivo. Taken together, our results indicate that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. PMID:27293993

Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy.

PubMed

Tang, Monica; Horsley, Patrick; Lewis, Craig R

2018-05-01

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018). © 2018 Royal Australasian College of Physicians.

A systematic review of barriers to early presentation and diagnosis with breast cancer among black women

PubMed Central

Jones, Claire EL; Maben, Jill; Jack, Ruth H; Davies, Elizabeth A; Forbes, Lindsay JL; Lucas, Grace; Ream, Emma

2014-01-01

Objective To explore barriers to early presentation and diagnosis with breast cancer among black women. Design Systematic review. Methods We searched multiple bibliographic databases (January 1991–February 2013) for primary research, published in English, conducted in developed countries and investigating barriers to early presentation and diagnosis with symptomatic breast cancer among black women (≥18 years). Studies were excluded if they did not report separate findings by ethnic group or gender, only reported differences in time to presentation/diagnosis, or reported on interventions and barriers to cancer screening. We followed Cochrane and PRISMA guidance to identify relevant research. Findings were integrated through thematic synthesis. Designs of quantitative studies made meta-analysis impossible. Results We identified 18 studies (6183 participants). Delay was multifactorial, individual and complex. Factors contributing to delay included: poor symptom and risk factor knowledge; fear of detecting breast abnormality; fear of cancer treatments; fear of partner abandonment; embarrassment disclosing symptoms to healthcare professionals; taboo and stigmatism. Presentation appears quicker following disclosure. Influence of fatalism and religiosity on delay is unclear from evidence in these studies. We compared older studies (≥10 years) with newer ones (<10 years) to determine changes over time. In older studies, delaying factors included: inaccessibility of healthcare services; competing priorities and concerns about partner abandonment. Partner abandonment was studied in older studies but not in newer ones. Comparisons of healthy women and cancer populations revealed differences between how people perceive they would behave, and actually behave, on finding breast abnormality. Conclusions Strategies to improve early presentation and diagnosis with breast cancer among black women need to address symptom recognition and interpretation of risk, as well as

Increased Detection of Lymphatic Vessel Invasion by D2-40 (Podoplanin) in Early Breast Cancer: Possible Influence on Patient Selection for Accelerated Partial Breast Irradiation

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

Debald, Manuel, E-mail: debald@uni-bonn.d; Poelcher, Martin; Flucke, Uta

2010-07-15

Purpose: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. Patients and Methods: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine themore » eligibility for APBI: invasive ductal adenocarcinoma of {<=}3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. Results: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). Conclusion: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.« less

Maternal accounts of their breast-feeding intent and early challenges after caesarean childbirth.

PubMed

Tully, Kristin P; Ball, Helen L

2014-06-01

breast-feeding outcomes are often worse after caesarean section compared to vaginal childbirth. this study characterises mothers' breast-feeding intentions and their infant feeding experiences after caesarean childbirth. data are from 115 mothers on a postnatal unit in Northeast England during February 2006-March 2009. Interviews were conducted an average of 1.5 days (range 1-6 days) after the women underwent unscheduled or scheduled caesarean. thematic analysis of the data suggested was mostly considered the 'right thing to do,' preferable, natural, and 'supposedly healthier,' but tiring and painful. Advantages of supplementation involved more satiated infants, feeding ease, and longer sleep bouts. The need for 'thinking about yourself' was part of caesarean recovery. Infrequent feeding was concerning but also enabled maternal rest. Other breast-feeding obstacles were maternal mobility limitations, positioning difficulties, and frustration at the need for assistance. Participants were confused about nocturnal infant wakings, leading many to determine that they had insufficient milk. Mothers were surprised that sub-clinically poor infant condition was common following caesarean section. Some breast-feeding difficulty stemmed from 'mucus' expulsion that had to occur before the infants could be 'interested' in feeding. Women who cited motivations for breast feeding that included benefit to themselves were more likely to exclusively breast feed on the postnatal unit after their caesareans than those who reported infant-only motivations. for the majority of mothers, breast feeding after a caesarean is affected by interrelated and compounding difficulties. Provision of more relational breast-feeding information may enable families to better anticipate early feeding experiences after caesarean section childbirth. © 2013 Elsevier Ltd. All rights reserved.

Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

PubMed

Dodd, Rachael H; Forster, Alice S; Sellars, Sarah; Patnick, Julietta; Ramirez, Amanda J; Forbes, Lindsay J L

2017-06-05

Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

Breast cancer in relation to childhood parental divorce and early adult psychiatric disorder in a British birth cohort.

PubMed

Lokugamage, A U; Hotopf, M; Hardy, R; Mishra, G; Butterworth, S; Wadsworth, M E J; Kuh, D

2006-09-01

Jacobs and Bovasso reported (Psychological Medicine 2000, 30, 669-678) that maternal death in childhood and chronic severe depression in adulthood were associated with subsequent breast cancer. We have examined the effects of parental loss in childhood and psychiatric disorder in adult life on breast cancer risk using a national birth cohort study. Eighty-three cases of breast cancer were diagnosed in a study of 2253 women followed from birth to age 59 years. Cox proportional hazards models were used to test whether breast cancer rates were higher in women who experienced parental death and divorce before age 16, psychiatric disorders between 15 and 32 years, symptoms of anxiety and depression at 36 years, or use of antidepressant medication at 31 or 36 years than in women who did not have these experiences. There was no overall association between parental death, parental divorce or psychiatric disorder and the incidence of breast cancer. There was some evidence that women with more severe psychiatric disorders between the ages of 15 and 32 years were more likely to develop breast cancer early. The interaction between parental divorce and severe psychiatric disorder was non-significant (p=0.1); however, the group who experienced both these events had an increased breast cancer risk compared with those who experienced neither [hazard ratio (HR) 2.64, 95% confidence interval (CI) 1.13-6.19]. Our study does not provide strong support for the hypothesis that early loss or adult psychiatric disorders are associated with breast cancer. A meta-analysis is needed that uses data from all available cohort studies and investigates possible interactive effects on breast cancer risk.

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

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

Chu, Tian-Li; Zhao, Hong-Meng; Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin

2014-04-04

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3more » expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.« less

The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan.

PubMed

Abdikhakimov, Abdulla; Tukhtaboeva, Mukaddas; Adilov, Bakhtiyar; Turdikulova, Shahlo

2016-01-01

Breast cancer is the most common malignancy in women and affects approximately 1 out of 8 females in the US. Risk of developing breast cancer is strongly influenced by genetic factors. Germ-line mutations in BRCA1 and BRCA2 genes are associated with 5-10% of breast cancer incidence. To reduce the risk of developing cancer and to increase the likelihood of early detection, carriers of BRCA1 or BRCA2 mutations are offered surveillance programs and effective preventive medical interventions. Identification of founder mutations of BRCA1/2 in high risk communities can have a significant impact on the management of hereditary cancer at the level of the national healthcare systems, making genetic testing more affordable and cost-effective. BRCA1 and BRCA2 mutations in breast cancer patients have not been characterized in the Uzbek population. This pilot study aimed to investigate the contribution of BRCA1 and BRCA2 mutation to early onset and familial cases of breast cancer in Uzbekistan. A total of 67 patients with breast cancer and 103 age-matched disease free controls were included in this study. Utilizing SYBR Green based real-time allele-specific PCR, we have analyzed DNA samples of patients with breast cancer and disease free controls to identify the following BRCA1 and BRCA2 mutations: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT. Three unrelated samples (4.5%) were found to be positive for the heterozygous 5382insCBRCA1 mutation, representing a possible founder mutation in the Uzbek population, supporting the need for larger studies examining the contribution of this mutation to breast cancer incidence in Uzbekistan. We did not find BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, and BRCA2 6174delT mutations. This preliminary evidence suggests a potential contribution of BRCA1 5382insC mutation to breast cancer development in Uzbek population. Taking into account a high disease penetrance in carriers of BRCA1 mutation, it seems

Duration of breast feeding and arterial distensibility in early adult life: population based study

PubMed Central

Leeson, C P M; Kattenhorn, M; Deanfield, J E; Lucas, A

2001-01-01

Objectives To test the hypothesis that duration of breast feeding is related to changes in vascular function relevant to the development of cardiovascular disease. Design Population based observational study. Setting Cambridge. Participants 331 adults (171 women, 160 men) aged between 20 and 28 years, born in Cambridge Maternity Hospital. Main outcome measures Distensibility of brachial artery, type and duration of infant feeding, current lipid profile, and other cardiovascular risk factors. Results The longer the period of breast feeding the less distensible the artery wall in early adult life, with no sex differences (regression coefficient = −3.93 μm/month, 95% confidence interval −7.29 to −0.57, P=0.02). However, in those breast fed for less than four months, arterial distensibility was not significantly reduced compared with an exclusively formula fed group. The vascular changes observed were not explained by alterations in plasma cholesterol concentration in adult life. Conclusions Breast feeding in infancy is related to reduced arterial function 20 years later. These data should not alter current recommendations in favour of breast feeding, which has several benefits for infant health. Further work is needed, however, to explore the optimal duration of breast feeding in relation to cardiovascular outcomes. PMID:11250848

Increasing patient involvement in choosing treatment for early breast cancer.

PubMed

Street, R L; Voigt, B; Geyer, C; Manning, T; Swanson, G P

1995-12-01

This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.

Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

PubMed

Hadji, P; Coleman, R E; Wilson, C; Powles, T J; Clézardin, P; Aapro, M; Costa, L; Body, J-J; Markopoulos, C; Santini, D; Diel, I; Di Leo, A; Cameron, D; Dodwell, D; Smith, I; Gnant, M; Gray, R; Harbeck, N; Thurlimann, B; Untch, M; Cortes, J; Martin, M; Albert, U-S; Conte, P-F; Ejlertsen, B; Bergh, J; Kaufmann, M; Holen, I

2016-03-01

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients. © 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.

Heparanase augments insulin receptor signaling in breast carcinoma

PubMed Central

Goldberg, Rachel; Sonnenblick, Amir; Hermano, Esther; Hamburger, Tamar; Meirovitz, Amichay; Peretz, Tamar; Elkin, Michael

2017-01-01

Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer. In the present study we analyzed clinical samples of breast carcinoma derived from diabetic/non-diabetic patients, and investigated effects of heparanase on insulin signaling in breast carcinoma cell lines, as well as insulin-driven growth of breast tumor cells. We demonstrate that heparanase activity leads to enhanced insulin signaling and activation of downstream tumor-promoting pathways in breast carcinoma cells. In agreement, heparanase enhances insulin-induced proliferation of breast tumor cells in vitro. Moreover, analyzing clinical data from diabetic breast carcinoma patients, we found that concurrent presence of both diabetic state and heparanase in tumor tissue (as opposed to either condition alone) was associated with more aggressive phenotype of breast tumors in the patient cohort analyzed in our study (two-sided Fisher's exact test; p=0.04). Our findings highlight the emerging role of heparanase in powering effect of hyperinsulinemic state on breast tumorigenesis and imply that heparanase targeting, which is now under intensive development/clinical testing, could be particularly efficient in a growing fraction of breast carcinoma patients suffering from metabolic disorders. PMID:28038446

RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

PubMed

Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

2016-08-01

Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

PubMed Central

McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

2016-01-01

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

PubMed

Morgan, E R; Laing, K; McCarthy, J; McCrate, F; Seal, M D

2015-10-01

Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Multifaceted Leptin network: the molecular connection between obesity and breast cancer

PubMed Central

Saxena, Neeraj K.; Sharma, Dipali

2016-01-01

High plasma levels of leptin, a major adipocytokine produced by adipocytes, are correlated with increased fat mass in obese state. Leptin is emerging as a key candidate molecule linking obesity with breast cancer. Acting via endocrine, paracrine, and autocrine manner, leptin impacts various stages of breast tumorigenesis from initiation and primary tumor growth to metastatic progression. Leptin also modulates the tumor microenvironment mainly through supporting migration of endothelial cells, neo-angiogenesis and sustaining recruitment of macrophage and monocytes. Various studies have shown that hyperactive leptin-signaling network leads to concurrent activation of multiple oncogenic pathways resulting in enhanced proliferation, decreased apoptosis, acquisition of mesenchymal phenotype, potentiated migration and enhanced invasion potential of tumor cells. Furthermore, the capability of leptin to interact with other molecular effectors of obese state including, estrogen, IGF-1, insulin, VEGF and inflammatory cytokines further increases its impact on breast tumor progression in obese state. This article presents an overview of the studies investigating the involvement of leptin in breast cancer. PMID:24214584

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer

PubMed Central

Greenup, Rachel A.; Blitzblau, Rachel C.; Houck, Kevin L.; Sosa, Julie Ann; Horton, Janet; Peppercorn, Jeffrey M.; Taghian, Alphonse G.; Smith, Barbara L.; Hwang, E. Shelley

2018-01-01

Introduction Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. Patients and Methods Using the National Cancer Database, we identified women with T1–T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. Results Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. Conclusion Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures. PMID:28291382

A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

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

Lin, Chaoyang; Zhang, Pengju; Jiang, Anli

C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover,more » C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.« less

Simultaneous detection of circulating immunological parameters and tumor biomarkers in early stage breast cancer patients during adjuvant chemotherapy.

PubMed

Rovati, B; Mariucci, S; Delfanti, S; Grasso, D; Tinelli, C; Torre, C; De Amici, M; Pedrazzoli, P

2016-06-01

Chemotherapy-induced immune suppression has mainly been studied in patients with advanced cancer, but the influence of chemotherapy on the immune system in early stage cancer patients has so far not been studied systematically. The aim of the present study was to monitor the immune system during anthracycline- and taxane-based adjuvant chemotherapy in early stage breast cancer patients, to assess the impact of circulating tumor cells on selected immune parameters and to reveal putative angiogenic effects of circulating endothelial cells. Peripheral blood samples from 20 early stage breast cancer patients were analyzed using a flow cytometric multi-color of antibodies to enumerate lymphocyte and dendritic cell subsets, as well as endothelial and tumor cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of various serological factors. During chemotherapy, all immunological parameters and angiogenesis surrogate biomarkers showed significant decreases. The numbers of circulating tumor cells showed significant inverse correlations with the numbers of T helper cells, a lymphocyte subset directly related to effective anti-tumor responses. Reduced T helper cell numbers may contribute to systemic immunosuppression and, as such, the activation of dormant tumor cells. From our results we conclude that adjuvant chemotherapy suppresses immune function in early stage breast cancer patients. In addition, we conclude that the presence of circulating tumor cells, defined as pan-cytokeratin(+), CD326(+), CD45(-) cells, may serve as an important indicator of a patient's immune status. Further investigations are needed to firmly define circulating tumor cells as a predictor for the success of breast cancer adjuvant chemotherapy.

Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice.

PubMed

Pierre, Christina C; Longo, Joseph; Mavor, Meaghan; Milosavljevic, Snezana B; Chaudhary, Roopali; Gilbreath, Ebony; Yates, Clayton; Daniel, Juliet M

2015-09-01

Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymeric composite devices for localized treatment of early-stage breast cancer

PubMed Central

Kan-Dapaah, Kwabena; Soboyejo, Wole

2017-01-01

For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment. PMID:28245288

Instrumental relating and treatment decision making among older women with early-stage breast cancer.

PubMed

Pieters, Huibrie C; Heilemann, Marysue V; Maliski, Sally; Dornig, Katrina; Mentes, Jan

2012-01-01

To understand how women aged 70 years and older who had recently undergone treatment for early-stage breast cancer experienced treatment decision making. Qualitative, descriptive study guided by grounded theory. PARTICIPANTS' houses and apartments in southern California. 18 women, aged 70-94 years, who completed treatment for primary, early-stage breast cancer 3-15 months prior (X = 8.5 months). Twenty-eight semistructured personal interviews that lasted, on average, 104 minutes. Data were collected and analyzed using constructivist grounded theory. Gero-oncology perspective of treatment decision making. A major finding was that the power of relating spontaneously was used as a vehicle to connect with others. That process, which the authors called "instrumental relating," was grounded in a foundation of mutual caring for themselves and others. Within that mutual caring, the women participated in three ways of relating to share in treatment decision making: obtaining information, interpreting healthcare providers, and determining the trustworthiness of their providers. Those ways of relating were effortlessly and simultaneously employed. The women used their expert abilities of relating to get the factual and emotional information that they needed. That information supported what the women perceived to be decisions that were shared and effective. The findings are the first evidence of the importance of relating as a key factor in decision making from the personal perspective of older women with early-stage breast cancer. This work serves as a springboard for future clinical interventions and research opportunities to individualize communication and enhance effective decision making for older patients who wish to participate in their cancer care.

Early uptake of breast magnetic resonance imaging in a community-based medical practice, 2000-2004.

PubMed

Stout, Natasha K; Nekhlyudov, Larissa

2011-04-01

Clinical applications of magnetic resonance imaging (MRI) of the breast have expanded across the breast cancer detection and control spectrum over the past decade. Use appears to be growing, although evidence for or against its use is still accumulating. Using electronic health plan and medical record data, we documented early trends in breast MRI use from 2000 through 2004 in a large community practice setting with approximately 82,000 eligible female patients. During the study period, 225 women received at least one breast MRI; of those, 64 had subsequent MRI (for a total of 333 MRIs). Utilization grew from 6 MRIs in 2000 to 112 in 2004, with increasing use for screening, diagnosis, disease staging/treatment, and surveillance purposes. Diagnostic use accounted for nearly half of the breast MRIs (164 of 333). In this community-based practice, there was rapid uptake of this new technology despite paucity of evidence about its uses. As new evidence is generated, use of this technology will need to be monitored to minimize the risk of overuse and unintended downstream consequences.

Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer.

PubMed

Grönberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fjällskog, Marie-Louise

2017-01-01

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial.

PubMed

Ignatiadis, Michail; Rack, Brigitte; Rothé, Francoise; Riethdorf, Sabine; Decraene, Charles; Bonnefoi, Hervé; Dittrich, Christian; Messina, Carlo; Beauvois, Melanie; Trapp, Elisabeth; Goulioti, Theodora; Tryfonidis, Konstantinos; Pantel, Klaus; Repollet, Madeline; Janni, Wolfgang; Piccart, Martine; Sotiriou, Christos; Litiere, Saskia; Pierga, Jean-Yves

2016-08-01

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine (NCT01548677). Copyright © 2016 Elsevier Ltd. All rights reserved.

Proceedings of the Department of Defense Breast Cancer Research Program Meeting for Era of Hope, Held in Baltimore, Maryland on 25-28 June 2008

DTIC Science & Technology

2008-06-01

well as the MMTV-Her2/neu trans- genic mouse model of breast tumorigenesis, nude mouse cleared fat pad and xenograft manipulations, shear rheology...women at greatest risk of disease recurrence, and identify mechanisms that mediate interactions among fat deposits and breast epithelia and that also...Matthew Johnson1 1University of Texas at Brownsville, 2Meharry Medical College, Nashville, and 3University of Louisville Obesity and body fat

Similar Survival With Breast Conservation Therapy or Mastectomy in the Management of Young Women With Early-Stage Breast Cancer

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

Mahmood, Usama, E-mail: usama.mahmood@gmail.com; Morris, Christopher; Neuner, Geoffrey

2012-08-01

Purpose: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: A total of 14,764 women weremore » identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). Conclusions: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.« less

PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis.

PubMed

Liu, Fabao; Ma, Fengfei; Wang, Yuyuan; Hao, Ling; Zeng, Hao; Jia, Chenxi; Wang, Yidan; Liu, Peng; Ong, Irene M; Li, Baobin; Chen, Guojun; Jiang, Jiaoyang; Gong, Shaoqin; Li, Lingjun; Xu, Wei

2017-11-01

Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP 3 Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP 3 R-dependent mitochondrial functions.

PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis

PubMed Central

Liu, Fabao; Ma, Fengfei; Wang, Yuyuan; Hao, Ling; Zeng, Hao; Jia, Chenxi; Wang, Yidan; Liu, Peng; Ong, Irene M; Li, Baobin; Chen, Guojun; Jiang, Jiaoyang; Gong, Shaoqin; Li, Lingjun; Xu, Wei

2017-01-01

Metabolic reprogramming is a hallmark of cancer. Herein we discovered that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondria calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol 1, 4, 5-trisphosphate receptors (IP3Rs), methylated PKM2 inhibits the influx of calcium from endoplasmic reticulum (ER) to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticle perturbs metabolic energy balance in cancer cells, leading to decrease of cell proliferation, migration, and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to IP3R-dependent mitochondrial functions. PMID:29058718

Systemic therapy for HER2-positive early-stage breast cancer.

PubMed

Mathew, Aju; Romond, Edward H

The advent of the targeted monoclonal antbody trastuzumab for treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer marked a revolution in the understanding and management of mammary carcinoma and, in practice, separated this subtype from other kinds of primary breast malignancy. Long term follow-up from the initial large adjuvant trials continue to show remarkably positive results. Currently, at least four additional agents targeting this receptor, using different and complementary mechanisms of action compared with trastuzumab, have been incorporated into clinical trials. The small molecule tyrosine kinase inhibitors lapatinib and neratinib, in addition to the antibody pertuzumab and the antibody-drug conjugate trastuzumab-ematansine, have shown efficacy in metastatic breast cancer and are being evaluated both in neoadjuvant and adjuvant trials for early stage disease. The cytotoxic chemotherapy regimens used in combination with these agents also are evolving and different therapeutic approaches are emerging for patients depending on their relative level of risk from their cancers, thus moving clinical management toward individualized therapy. Much has been learned about managing the toxicities of treatment and pre-operative approaches have provided a means of assessing the sensitivity of individual patients' cancers to specific treatment regimens. This review traces the development of these studies and focuses on improvements in adjuvant and neoadjuvant therapy for patients with HER2-positive disease whose prognosis has changed in the last decade from dire to favorable. A path forward has been set by which the goal of cure is attainable for almost all patients faced with this aggressive form of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

PubMed

Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

2018-01-01

A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

Standardization of infrared breast thermogram acquisition protocols and abnormality analysis of breast thermograms

NASA Astrophysics Data System (ADS)

Bhowmik, Mrinal Kanti; Gogoi, Usha Rani; Das, Kakali; Ghosh, Anjan Kumar; Bhattacharjee, Debotosh; Majumdar, Gautam

2016-05-01

The non-invasive, painless, radiation-free and cost-effective infrared breast thermography (IBT) makes a significant contribution to improving the survival rate of breast cancer patients by early detecting the disease. This paper presents a set of standard breast thermogram acquisition protocols to improve the potentiality and accuracy of infrared breast thermograms in early breast cancer detection. By maintaining all these protocols, an infrared breast thermogram acquisition setup has been established at the Regional Cancer Centre (RCC) of Government Medical College (AGMC), Tripura, India. The acquisition of breast thermogram is followed by the breast thermogram interpretation, for identifying the presence of any abnormality. However, due to the presence of complex vascular patterns, accurate interpretation of breast thermogram is a very challenging task. The bilateral symmetry of the thermal patterns in each breast thermogram is quantitatively computed by statistical feature analysis. A series of statistical features are extracted from a set of 20 thermograms of both healthy and unhealthy subjects. Finally, the extracted features are analyzed for breast abnormality detection. The key contributions made by this paper can be highlighted as -- a) the designing of a standard protocol suite for accurate acquisition of breast thermograms, b) creation of a new breast thermogram dataset by maintaining the protocol suite, and c) statistical analysis of the thermograms for abnormality detection. By doing so, this proposed work can minimize the rate of false findings in breast thermograms and thus, it will increase the utilization potentiality of breast thermograms in early breast cancer detection.

Small molecule inhibitors reveal PTK6 kinase is not an oncogenic driver in breast cancers

PubMed Central

Gajiwala, Ketan S.; Cronin, Ciarán N.; Nagata, Asako; Johnson, Eric; Kraus, Michelle; Tatlock, John; Kania, Robert; Foley, Timothy

2018-01-01

Protein tyrosine kinase 6 (PTK6, or BRK) is aberrantly expressed in breast cancers, and emerging as an oncogene that promotes tumor cell proliferation, migration and evasion. Both kinase-dependent and -independent functions of PTK6 in driving tumor growth have been described, therefore targeting PTK6 kinase activity by small molecule inhibitors as a therapeutic approach to treat cancers remains to be validated. In this study, we identified novel, potent and selective PTK6 kinase inhibitors as a means to investigate the role of PTK6 kinase activity in breast tumorigenesis. We report here the crystal structures of apo-PTK6 and inhibitor-bound PTK6 complexes, providing the structural basis for small molecule interaction with PTK6. The kinase inhibitors moderately suppress tumor cell growth in 2D and 3D cell cultures. However, the tumor cell growth inhibition shows neither correlation with the PTK6 kinase activity inhibition, nor the total or activated PTK6 protein levels in tumor cells, suggesting that the tumor cell growth is independent of PTK6 kinase activity. Furthermore, in engineered breast tumor cells overexpressing PTK6, the inhibition of PTK6 kinase activity does not parallel the inhibition of tumor cell growth with a >500-fold shift in compound potencies (IC50 values). Overall, these findings suggest that the kinase activity of PTK6 does not play a significant role in tumorigenesis, thus providing important evidence against PTK6 kinase as a potential therapeutic target for breast cancer treatment. PMID:29879184

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

PubMed Central

Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

2012-01-01

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

Circulating tumoral cells lack circadian-rhythm in hospitalized metastasic breast cancer patients.

PubMed

García-Sáenz, José Angel; Martín, Miguel; Maestro, Marisa; Vidaurreta, Marta; Veganzones, Silvia; Villalobos, Laura; Rodríguez-Lajusticia, Laura; Rafael, Sara; Sanz-Casla, María Teresa; Casado, Antonio; Sastre, Javier; Arroyo, Manuel; Díaz-Rubio, Eduardo

2006-11-01

The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in observational studies. Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients. CTC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers. No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

PubMed

Tonini, Gian Paolo

2017-01-05

Neuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors. In the present report it is proposed that chromosome instability (CIN) plays a major role in Neuroblastoma tumorigenesis and that CIN is already present in the early phases of tumor development. High CIN can promote several types of chromosomal damage including chromothripsis, gene deletion, amplification and rearrangements, which deregulate gene expression. Indeed, gene rearrangements have been reported as a new scenario in the development of Neuroblastoma, which supports the hypothesis that CIN is an early step preliminary to the late catastrophic events leading to tumor development.

Breast-feeding and hospitalization for asthma in early childhood: a nationwide longitudinal survey in Japan.

PubMed

Yamakawa, Michiyo; Yorifuji, Takashi; Kato, Tsuguhiko; Yamauchi, Yoshitada; Doi, Hiroyuki

2015-07-01

Whether or not breast-feeding is protective against asthma among children is still controversial. Therefore, we examined the effects of breast-feeding on hospitalization for asthma in early childhood. Secondary data analyses of a nationwide longitudinal survey of children in Japan ongoing since 2001, with results collected from 2001 to 2004. We used logistic regression models to evaluate the associations of breast-feeding with hospitalization for asthma in children between the ages of 6 and 42 months, adjusting for children's factors (sex, day-care attendance and presence of older siblings) and maternal factors (educational attainment and smoking habit). Setting All over Japan. Term singleton children with information on feeding practices during infancy (n 43367). After adjusting for maternal factors and children's factors, exclusive breast-feeding at 6-7 months of age was associated with decreased risk of hospitalization for asthma in children. The adjusted odds ratio was 0.77 (95% CI 0.56, 1.06). One-month longer duration of breast-feeding was associated with a 4% decreased risk of hospitalization for asthma (OR = 0.96; 95% CI 0.92, 0.99). The protective effects of breast-feeding on hospitalization for asthma were observed in children between the ages of 6 and 42 months.

Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

DTIC Science & Technology

2006-07-01

the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin...and rates of breast cancer initiation and progression. 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin , MPA, DMBA, Activin receptor 16...including interleukins, Insulin-like Growth Factor (IGF) isoforms, IGF-binding proteins and myostatin . To determine the effect of skeletal muscle mass

Cost implications of unwarranted imaging for distant metastasis in women with early-stage breast cancer in Ontario.

PubMed

Thavorn, K; Wang, Z; Fergusson, D; van Katwyk, S; Arnaout, A; Clemons, M

2016-02-01

Despite the publication of multiple evidence-based guidelines recommending against routine imaging for distant metastasis in patients with early-stage (i/ii) breast cancer, such imaging is frequently performed. The present retrospective cohort study was conducted to estimate the cost of unnecessary imaging tests in women with stage i and ii breast cancer diagnosed between 1 January 2007 and 31 December 2012 in Ontario. We obtained patient-level demographic and tumour data from a large provincial dataset. The total cost of unwarranted imaging tests (in 2015 Canadian dollars) was considered to be equal to the sum of imaging costs incurred between 2007 and 2012 and was stratified by disease stage, imaging modality, and body site. Of the 26,547 identified patients with early-stage breast cancer, 22,811 (85.9%) underwent at least 1 imaging test, with an average of 3.7 tests per patient (3.2 for stage i patients and 4.0 for stage ii patients) over 5 years. At least 1 imaging test was performed in 79.6% of stage i and 92.7% of stage ii patients. During a 5-year period, the cost of unwarranted imaging in patients with early-stage breast cancer ranged from CA$4,418,139 to CA$6,865,856, depending on guideline recommendations. Our study highlights the substantial cost of excess imaging that could be saved and re-allocated to patient care if evidence-based guidelines are followed. Future studies should assess strategies to ensure that evidence-based guidelines are followed and to increase awareness of the cost implications of nonadherence to guidelines.

Accelerated partial breast irradiation for elderly women with early breast cancer: A compromise between whole breast irradiation and omission of radiotherapy.

PubMed

Sumodhee, Shakeel; Levy, Johan; Chamorey, Emmanuel; Lam Cham Kee, Daniel; Chand, Marie-Eve; Gautier, Mathieu; Peyrottes, Isabelle; Barranger, Emmanuel; Hannoun-Levi, Jean-Michel

Regarding adjuvant radiation therapy making decision for elderly women, Albert (2013) published a nomogram predicting the mastectomy-free survival (MFS) rate with or without adjuvant irradiation. Based on this approach, we proposed to investigate the use of accelerated partial breast irradiation (APBI) vs. whole breast irradiation (WBI) or endocrine therapy alone in elderly low-risk breast cancer patients. For each elderly woman treated by conserving surgery and APBI (multicatheter interstitial high-dose-rate brachytherapy), 5- and 10-year MFS rates were calculated. For each treated patient, using the Albert nomogram, we calculated the estimated MFS rates at 5 and 10 years, with and without WBI. Then, we compared the estimated MFS rates after no irradiation and WBI vs. observed MFS rates after APBI. From 2005 to 2016, 79 patients were treated. Median followup was 96.8 months [68.6-104.9], median age was 77 years [66-89]. Expected 5- and 10-year mastectomy rates calculated with the Albert nomogram without WBI were 2.95% and 7.25%, respectively, leading to a 10-year MFS rate of 92.7%. Expected 5- and 10-year mastectomy rates after WBI were 1.41% and 3.66%, respectively, leading to a 10-year MFS rate of 96.3%. Regarding observed MFS rate, 1 pt (1.3%) experienced a salvage mastectomy. The 10-year MFS rate after APBI was 97.4% vs. 96.3% after WBI (p = 1) and 92.7% after no irradiation (p = 0.27). No toxicity Grade 3 or more was observed. APBI seems to be an attractive compromise between WBI and no irradiation for elderly women with early stage breast cancer as far as local control, quality of life and cost benefit is concerned. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

[Economic assessment of the routine use of Oncotype DX® assay for early breast cancer in Franche-Comte region].

PubMed

Nerich, Virginie; Curtit, Elsa; Bazan, Fernando; Montcuquet, Philippe; Villanueva, Cristian; Chaigneau, Loïc; Cals, Laurent; Méneveau, Nathalie; Dobi, Erion; Altmotlak, Hamadi; Algros, Marie-Paule; Choulot, Marie-Jeanne; Nallet, Gilles; Limat, Samuel; Mansion, Sylvie; Pivot, Xavier

2014-01-01

Oncotype DX® has been validated as quantifying the likelihood of distant recurrence at 10 years and overall chemotherapy benefit in patients with estrogen-receptor-positive and HER-2-negative early breast cancer. In 2012, this genomic signature was routinely available for patients in Franche-Comté, France. Patients eligible for Oncotype DX(®) testing had a ER-positive, HER-2-négative early breast cancer with a nodal involvement limited to 0 or 1 positive-node without extracapsular spread; an adjuvant chemotherapy was indicated based on usual prognostic factors. The aim was to assess the economic impact of Oncotype DX(®) testing in a French region. A cost-minimisation analysis from the French Public Healthcare System perspective was performed. The availability of Oncotype DX(®) in Franche-Comté, France, and its use in clinical routine allowed a decrease of 73 % of adjuvant chemotherapy without increase of the cost of the patients' management and with a potential reduction of the cost for the French Public Healthcare System. This strategy was successful and may allow the reimbursement of this test in France for patients with early breast cancer.

Factors influencing the surgery intentions and choices of women with early breast cancer: the predictive utility of an extended theory of planned behaviour

PubMed Central

2013-01-01

Background Women diagnosed with early breast cancer (stage I or II) can be offered the choice between mastectomy or breast conservation surgery with radiotherapy due to equivalence in survival rates. A wide variation in the surgical management of breast cancer and a lack of theoretically guided research on this issue highlight the need for further research into the factors influencing women’s choices. An extended Theory of Planned Behaviour (TPB) could provide a basis to understand and predict women’s surgery choices. The aims of this study were to understand and predict the surgery intentions and choices of women newly diagnosed with early breast cancer, examining the predictive utility of an extended TPB. Methods Sixty-two women recruited from three UK breast clinics participated in the study; 48 women, newly diagnosed with early breast cancer, completed online questionnaires both before their surgery and after accessing an online decision support intervention (BresDex). Questionnaires assessed views about breast cancer and the available treatment options using items designed to measure constructs of an extended TPB (i.e., attitudes, subjective norms, perceived behavioural control, and anticipated regret), and women’s intentions to choose mastectomy or BCS. Objective data were collected on women’s choice of surgery via the clinical breast teams. Multiple and logistic regression analyses examined predictors of surgery intentions and subsequent choice of surgery. Results The extended TPB accounted for 69.9% of the variance in intentions (p <.001); attitudes and subjective norms were significant predictors. Including additional variables revealed anticipated regret to be a more important predictor than subjective norms. Surgery intentions significantly predicted surgery choices (p <.01). Conclusions These findings demonstrate the utility of an extended TPB in predicting and understanding women’s surgery intentions and choices for early breast cancer

MiR-300 regulate the malignancy of breast cancer by targeting p53.

PubMed

Xu, Xiao-Heng; Li, Da-Wei; Feng, Hui; Chen, Hong-Mei; Song, Yan-Qiu

2015-01-01

In this study, we investigated the role of miR-300 in regulating cell proliferation and invasion of breast cancer (BC) cells. MicroRNA and protein expression patterns were compared between breast cancer tissue and normal tissue and between two different prognostic groups. The up-regulation of miR-300 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in MCF-7 breast cancer cells. We observed that miR-300 expression was frequently and dramatically up-regulated in human breast cancer tissues and cell lines compared with the matched adjacent normal tissues and cells. We further showed that transient and stable over-expression of miR-300 could promote cell proliferation and cell cycle progression. Moreover, p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting that miR-300 might promote breast cancer cell proliferation and invasion by regulating p53 expression. Our findings indicated that miR-300 up-regulation might exert some sort of antagonistic function by targeting p53 in breast cancer cell proliferation during breast tumorigenesis.

MiR-300 regulate the malignancy of breast cancer by targeting p53

PubMed Central

Xu, Xiao-Heng; Li, Da-Wei; Feng, Hui; Chen, Hong-Mei; Song, Yan-Qiu

2015-01-01

Objective: In this study, we investigated the role of miR-300 in regulating cell proliferation and invasion of breast cancer (BC) cells. Methods: MicroRNA and protein expression patterns were compared between breast cancer tissue and normal tissue and between two different prognostic groups. The up-regulation of miR-300 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in MCF-7 breast cancer cells. Results: We observed that miR-300 expression was frequently and dramatically up-regulated in human breast cancer tissues and cell lines compared with the matched adjacent normal tissues and cells. We further showed that transient and stable over-expression of miR-300 could promote cell proliferation and cell cycle progression. Moreover, p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting that miR-300 might promote breast cancer cell proliferation and invasion by regulating p53 expression. Conclusion: Our findings indicated that miR-300 up-regulation might exert some sort of antagonistic function by targeting p53 in breast cancer cell proliferation during breast tumorigenesis. PMID:26221232

Advanced detection and measurement of cells on membrane from peripheral blood by laser scanning cytometry (LSC) in early stage breast cancer patients.

PubMed

Sanislo, L; Kuliffay, P; Sedlak, J; Kausitz, J; Galbavy, S

2010-01-01

The aim of our study was the potential detection of circulating tumour cells (CTCs) in early stage breast cancer patients. Our approach was cell microfiltration through polycarbonate membrane as a concentration method suitable for CTC selection in peripheral blood. The isolated cells on membrane were further analysed by laser scanning cytometry. Sixteen patients were enrolled in the study, of which 13 had early stage breast carcinoma and 3 patients had metastatic breast carcinoma. The analyses were performed from 9 ml of peripheral blood, in one patient blood was drawn twice. Blood samples were taken after adjuvant chemotherapy but prior to adjuvant radiotherapy. The control group consisted of 12 clinically healthy subjects. In the control group 3 subjects out of 12 had 1 CTC, the mean CTC numbers being 0.25 +/- 0.45. In the early stage breast cancer patients 0-36 CTCs were detected (mean 13.9 +/- 12.9 CTCs. 10 patients out of 13 had more than 2 CTCs (62%). The detection and measurement of cells on membrane is a simple and reproducible method of detection of CTCs in peripheral blood. Sensitivity of the method is 88.5%. Detection of CTCs seems to be a promising method for the monitoring of adjuvant therapy in early stage breast cancer patients and for the identification of high risk patients in whom elevated numbers of CTCs are persisting following the termination of adjuvant therapy (Tab. 1, Fig. 4, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

COT phosphorylates prolyl-isomerase Pin1 to promote tumorigenesis in breast cancer.

PubMed

Kim, Garam; Khanal, Prem; Kim, Jin Young; Yun, Hyo-Jeong; Lim, Sung-Chul; Shim, Jung-Hyun; Choi, Hong Seok

2015-06-01

Pin1, a conserved eukaryotic Peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation, little is known about the upstream signaling pathway(s) that regulates Pin1 activity. Here, we identify MAP3K-related serine-threonine kinase (the gene encoding COT/Tpl2) as a kinase responsible for phosphorylation of Pin1 Ser16. COT interacts with and phosphorylates Pin1 on Ser16. Consequently, Pin1 Ser16 phosphorylation by COT increases cyclin D1 abundance and enhances tumorigenecity of MCF7 cells. In contrast, depletion of COT in MCF7 cells leads to downregulation of Pin1 Ser16 phosphorylation, which subsequently decrease cyclin D1 levels, inhibiting tumorigenecity of MCF7 cells. In a xenograft model, treatment of TKI, a COT inhibitor, and Juglone, a Pin1 inhibitor, abrogates tumor growth. In human breast cancer patients, immunohistochemical staining shows that Pin1 pSer16 levels are positively correlated with COT levels, providing strong evidence for an essential role of the COT/Pin1 axis in conveying oncogenic signals to promote aggressiveness in human breast cancer. © 2013 Wiley Periodicals, Inc.

Long-term impact of breast-feeding on body weight and glucose tolerance in children of diabetic mothers: role of the late neonatal period and early infancy.

PubMed

Rodekamp, Elke; Harder, Thomas; Kohlhoff, Rainer; Franke, Kerstin; Dudenhausen, Joachim W; Plagemann, Andreas

2005-06-01

Offspring of diabetic mothers (ODM) are at increased risk of developing overweight and impaired glucose tolerance (IGT). Recently, we observed that early neonatal ingestion of breast milk from diabetic mothers (DBM) may dose-dependently increase the risk of overweight in childhood. Here, we investigate whether DBM intake during the late neonatal period and early infancy also influences later adipogenic and diabetogenic risk in ODM. A total of 112 ODM were evaluated for influence of DBM ingestion during the late neonatal period (2nd-4th neonatal week) and early infancy on relative body weight (RBW) and glucose tolerance in early childhood. Exclusive breast-feeding was associated with increased childhood RBW (P = 0.011). Breast-fed ODM had an increased risk of overweight (odds ratio 1.98 [95% CI 1.12-3.50]). Breast-feeding duration was also positively related to childhood RBW (P = 0.004) and 120-min blood glucose during an oral glucose tolerance test (P = 0.022). However, adjustment for the DBM volume ingested during the early neonatal period, i.e., 1st week of life, eliminated all these relations with late neonatal breast-feeding and its duration. Interestingly, no relationship was observed between maternal blood glucose in the middle of the third trimester and the outcome. Neither late neonatal DBM intake nor the duration of breast-feeding has an independent influence on childhood risk of overweight or IGT in ODM. Therefore, the 1st week of life appears to be the critical window for nutritional programming in ODM by ingestion of maternal "diabetic" breast milk.

The Potential Role of Senescence As a Modulator of Platelets and Tumorigenesis

PubMed Central

Valenzuela, Claudio A.; Quintanilla, Ricardo; Moore-Carrasco, Rodrigo; Brown, Nelson E.

2017-01-01

In addition to thrombus formation, alterations in platelet function are frequently observed in cancer patients. Importantly, both thrombus and tumor formation are influenced by age, although the mechanisms through which physiological aging modulates these processes remain poorly understood. In this context, the potential effects of senescent cells on platelet function represent pathophysiological mechanisms that deserve further exploration. Cellular senescence has traditionally been viewed as a barrier to tumorigenesis. However, far from being passive bystanders, senescent cells are metabolically active and able to secrete a variety of soluble and insoluble factors. This feature, known as the senescence-associated secretory phenotype (SASP), may provide senescent cells with the capacity to modify the tissue environment and, paradoxically, promote proliferation and neoplastic transformation of neighboring cells. In fact, the SASP-dependent ability of senescent cells to enhance tumorigenesis has been confirmed in cellular systems involving epithelial cells and fibroblasts, leaving open the question as to whether similar interactions can be extended to other cellular contexts. In this review, we discuss the diverse functions of platelets in tumorigenesis and suggest the possibility that senescent cells might also influence tumorigenesis through their ability to modulate the functional status of platelets through the SASP. PMID:28894697

Regional Nodal Irradiation in Early-Stage Breast Cancer.

PubMed

Whelan, Timothy J; Olivotto, Ivo A; Parulekar, Wendy R; Ackerman, Ida; Chua, Boon H; Nabid, Abdenour; Vallis, Katherine A; White, Julia R; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J; Manchul, Lee; Chafe, Susan; Nolan, Maureen C; Craighead, Peter; Bowen, Julie; McCready, David R; Pritchard, Kathleen I; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W; Chen, Bingshu E; Levine, Mark N

2015-07-23

Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Dosimetric comparison of normal structures associated with accelerated partial breast irradiation and whole breast irradiation delivered by intensity modulated radiotherapy for early breast cancer after breast conserving surgery.

PubMed

Wu, S; He, Z; Guo, J; Li, F; Lin, Q; Guan, X

2014-01-01

To assess the heart and lung dosimetry results associated with accelerated partial breast irradiation intensity-modulated radiotherapy (APBI-IMRT) and whole breast field-in-field intensity-modulated radiotherapy (WBI-FIF-IMRT). A total of 29 patients with early-stage breast cancer after lumpectomy were included in this study. APBI-IMRT and WBI-FIF-IMRT plans were generated for each patient. The dosimetric parameters of ipsilateral lung and heart in both plans were then compared with and without radiobiological correction. With and without radiobiological correction, the volume of ipsilateral lung showed a substantially lower radiation exposure in APBI-IMRT with moderate to high doses (P < 0.05) but non-significant increases in volume of ipsilateral lung in 2.5 Gy than WBI-FIF-IMRT (P > 0.905).There was no significant difference in volume of ipsilateral lung receiving 1, 2.5, and 5 Gy between APBI-IMRT and WBI (P > 0.05) in patients with medial tumor location, although APBI-IMRT exposed more lung to 2.5 and 5 Gy. APBI-IMRT significantly decreases the volume of heart receiving low to high doses in left-sided breast cancer (P < 0.05). APBI-IMRT can significantly spare the volume of heart and ipsilateral lung receiving moderate and high dose. Non-significant increases in volume of the ipsilateral lung exposed to low doses of radiation were observed for APBI-IMRT in comparison to WBI-FIF-IMRT, particularly in patients with medial tumor location. With the increasing interest in APBI-IMRT, our data may help clinicians individualize patient treatment decisions.

Cosmesis and Breast-Related Quality of Life Outcomes After Intraoperative Radiation Therapy for Early Breast Cancer: A Substudy of the TARGIT-A Trial

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

Corica, Tammy, E-mail: Tammy.Corica@health.wa.gov.au; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia; Nowak, Anna K.

Purpose: To report the first comprehensive investigation of patient-reported cosmesis and breast-related quality of life (QOL) outcomes comparing patients randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial. Methods and Materials: Longitudinal cosmesis and QOL data were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology). Patients completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Patients also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Imagemore » after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision. Results: An Excellent–Good cosmetic result was scored more often than a Fair–Poor result for both treatment groups across all time points. The TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month 6 and year 1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT patients at these time points. Conclusion: Patients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision-making process for patients who have early breast cancer suitable for breast-conserving surgery and inform their clinicians.« less

HIP1: trafficking roles and regulation of tumorigenesis.

PubMed

Hyun, Teresa S; Ross, Theodora S

2004-04-01

During recent years, alterations in proteins of the endocytic pathway have been associated with tumors. Disrupted regulation of the endocytic pathway is a relatively unstudied mechanism of tumorigenesis, which can concomitantly disrupt several different signaling pathways to affect growth, differentiation and survival. Several endocytic proteins have been identified, either as part of tumor-associated translocations or to have the ability to transform cells. Here, we summarize the information known about huntingtin interacting protein 1 (HIP1), an endocytic protein with transforming properties that is involved in a cancer-causing translocation and which is overexpressed in a variety of human cancers. We describe the known normal functions of HIP1 in endocytosis and receptor trafficking, the evidence for its role as an oncoprotein and how HIP1 might be altered to promote tumorigenesis.

Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

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

Sun, Lin; Li, Yu; Yang, Bangxiang, E-mail: b19933009@qq.coom

Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition ofmore » proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.« less

Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

PubMed

Nguyen-Dumont, Tú; Teo, Zhi L; Hammet, Fleur; Roberge, Alexis; Mahmoodi, Maryam; Tsimiklis, Helen; Park, Daniel J; Pope, Bernard J; Lonie, Andrew; Kapuscinski, Miroslav K; Mahmood, Khalid; Goldgar, David E; Giles, Graham G; Winship, Ingrid; Hopper, John L; Southey, Melissa C

2018-02-08

Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p < 0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

True Local Recurrences after Breast Conserving Surgery have Poor Prognosis in Patients with Early Breast Cancer

PubMed Central

Sarsenov, Dauren; Ilgun, Serkan; Ordu, Cetin; Alco, Gul; Bozdogan, Atilla; Elbuken, Filiz; Nur Pilanci, Kezban; Agacayak, Filiz; Erdogan, Zeynep; Eralp, Yesim; Dincer, Maktav

2016-01-01

Background: This study was aimed at investigating clinical and histopathologic features of ipsilateral breast tumor recurrences (IBTR) and their effects on survival after breast conservation therapy. Methods: 1,400 patients who were treated between 1998 and 2007 and had breast-conserving surgery (BCS) for early breast cancer (cT1-2/N0-1/M0) were evaluated. Demographic and pathologic parameters, radiologic data, treatment, and follow-up related features of the patients were recorded. Results: 53 patients (3.8%) had IBTR after BCS within a median follow-up of 70 months. The mean age was 45.7 years (range, 27-87 years), and 22 patients (41.5%) were younger than 40 years. 33 patients (62.3%) had true recurrence (TR) and 20 were classified as new primary (NP). The median time to recurrence was shorter in TR group than in NP group (37.0 (6-216) and 47.5 (11-192) months respectively; p = 0.338). Progesterone receptor positivity was significantly higher in the NP group (p = 0.005). The overall 5-year survival rate in the NP group (95.0%) was significantly higher than that of the TR group (74.7%, p < 0.033). Multivariate analysis showed that younger age (<40 years), large tumor size (>20 mm), high grade tumor and triple-negative molecular phenotype along with developing TR negatively affected overall survival (hazard ratios were 4.2 (CI 0.98-22.76), 4.6 (CI 1.07-13.03), 4.0 (CI 0.68-46.10), 6.5 (CI 0.03-0.68), and 6.5 (CI 0.02- 0.80) respectively, p < 0.05). Conclusions: Most of the local recurrences after BCS in our study were true recurrences, which resulted in a poorer outcome as compared to new primary tumors. Moreover, younger age (<40), large tumor size (>2 cm), high grade, triple negative phenotype, and having true recurrence were identified as independent prognostic factors with a negative impact on overall survival in this dataset of patients with recurrent breast cancer. In conjunction with a more intensive follow-up program, the role of adjuvant therapy

77 FR 66469 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the following meeting of...

Outcomes in Black Patients With Early Breast Cancer Treated With Breast Conservation Therapy

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

Nichols, Michael A.; Mell, Loren K.; Hasselle, Michael D.

Background: The race-specific impact of prognostic variables for early breast cancer is unknown for black patients undergoing breast conservation. Methods and Materials: This was a retrospective study of 1,231 consecutive patients {>=}40 years of age with Stage I-II invasive breast cancer treated with lumpectomy and radiation therapy at the University of Chicago Hospitals and affiliates between 1986 and 2004. Patients were classified as either black or nonblack. Cox proportional hazards regression was used to model the effects of known prognostic factors and interactions with race. Results: Median follow-up for surviving patients was 82 months. Thirty-four percent of patients were black,more » and 66% were nonblack (Caucasian, Hispanic, and Asian). Black patients had a poorer 10-year overall survival (64.6% vs. 80.8%; adjusted hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.23-2.06) and 10-year disease-free survival (58.1% vs. 75.4%; HR 1.49; 95% CI, 1.18-1.89) compared with nonblack patients. Tumor sizes were similar between nonblack and black patients with mammographically detected tumors (1.29 cm vs. 1.20 cm, p = 0.20, respectively). Tumor size was significantly associated with overall survival (HR 1.48; 95% CI, 1.12-1.96) in black patients with mammographically detected tumors but not in nonblack patients (HR 1.09; 95% CI, 0.78-1.53), suggesting that survival in black patients depends more strongly on tumor size in this subgroup. Tests for race-size method of detection interactions were statistically significant for overall survival (p = 0.049), locoregional control (p = 0.036), and distant control (p = 0.032) and borderline significant for disease-free survival (p = 0.067). Conclusion: Despite detection at comparable sizes, the prognostic effect of tumor size in patients with mammographically detected tumors is greater for black than in nonblack patients.« less

Attitude and Practice Regarding Breast Cancer Early Detection among Iranian Women: A Systematic Review

PubMed Central

Badakhsh, Mahin; Balouchi, Abbas; Taheri, Safiyeh; Bouya, Salehoddin; Ahmadidarehsima, Sudabeh; Aminifard, Mohammadnaem

2018-01-01

Objectives: To determining attitudes and practice regarding breast cancer early detection techniques (breast self-examination (BSE), clinical breast examination (CBE) and mammography) among Iranian woman. Methods: International (PubMed, ISI, and Google Scholar) and national (SID and Magiran) databases were reviewed up to September 2017 to identify articles related to the attitudes and practices of Iranian women concerning breast cancer screening behavior with reference to BSE , CBE and mammography. The screening steps, analysis of quality of the studies and extraction of the papers were performed by two reviewers. Results: Of the 532 studies included initially, 21 performed on 10,521 people were considered eligible. Subjects with a positive attitude toward BSE in various studies were 13.5% to 94.0% with an average of 47.6%. Positive attitudes to CBE and mammography were found in 21.0% and 26.4%, respectively. Participant performance of BSE ranged from 2.6% to 84.7%, with an average of 21.9%. The respective figures for CBE and mammography were 15.8% and 16.7%. Conclusion: Considering the poor performance and low rates for positive attitudes, it is suggested that educational programs should be conducted across the country. PMID:29373873

Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research.

PubMed

Liu, Jianlin; Adhav, Ragini; Xu, Xiaoling

2017-01-01

Breast cancers display striking genetic and phenotypic diversities. To date, several hypotheses are raised to explain and understand the heterogeneity, including theories for cancer stem cell (CSC) and clonal evolution. According to the CSC theory, the most tumorigenic cells, while maintaining themselves through symmetric division, divide asymmetrically to generate non-CSCs with less tumorigenic and metastatic potential, although they can also dedifferentiate back to CSCs. Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. During tumorigenesis and evolution process, cancer cells undergo different degrees of genetic instability and consequently obtain varied genetic aberrations. Yet the heterogeneity in breast cancers is very complex, poorly understood and subjected to further investigation. In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast cancer therapies. In this review, we will summarize development of SCS technologies and recent advances of SCS in breast cancer.

Early Stage Breast Cancer in Older Women: Predictors and Outcomes of Therapy

DTIC Science & Technology

2001-10-01

undergoing at least the The use of breast-conserving surgery increased during minimum appropriate primary treatment (defined, in the early 1980s ,3...remained generally stable during the late accordance with the recommendations of a National 1980s ,4’, and increased further from about 1990 Institutes of...receiving appropriate primary therapy was about 88% was classified as white, black, or other. The size of until the late 1980s (figure 1); it then

Methylation analysis of plasma cell-free DNA for breast cancer early detection using bisulfite next-generation sequencing.

PubMed

Li, Zibo; Guo, Xinwu; Tang, Lili; Peng, Limin; Chen, Ming; Luo, Xipeng; Wang, Shouman; Xiao, Zhi; Deng, Zhongping; Dai, Lizhong; Xia, Kun; Wang, Jun

2016-10-01

Circulating cell-free DNA (cfDNA) has been considered as a potential biomarker for non-invasive cancer detection. To evaluate the methylation levels of six candidate genes (EGFR, GREM1, PDGFRB, PPM1E, SOX17, and WRN) in plasma cfDNA as biomarkers for breast cancer early detection, quantitative analysis of the promoter methylation of these genes from 86 breast cancer patients and 67 healthy controls was performed by using microfluidic-PCR-based target enrichment and next-generation bisulfite sequencing technology. The predictive performance of different logistic models based on methylation status of candidate genes was investigated by means of the area under the ROC curve (AUC) and odds ratio (OR) analysis. Results revealed that EGFR, PPM1E, and 8 gene-specific CpG sites showed significantly hypermethylation in cancer patients' plasma and significantly associated with breast cancer (OR ranging from 2.51 to 9.88). The AUC values for these biomarkers were ranging from 0.66 to 0.75. Combinations of multiple hypermethylated genes or CpG sites substantially improved the predictive performance for breast cancer detection. Our study demonstrated the feasibility of quantitative measurement of candidate gene methylation in cfDNA by using microfluidic-PCR-based target enrichment and bisulfite next-generation sequencing, which is worthy of further validation and potentially benefits a broad range of applications in clinical oncology practice. Quantitative analysis of methylation pattern of plasma cfDNA by next-generation sequencing might be a valuable non-invasive tool for early detection of breast cancer.

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

PubMed

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-09-04

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

PubMed

Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2014-02-01

Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Deviation from the Standard of Care for Early Breast Cancer in the Elderly: What are the Consequences?

PubMed

Sun, Susie X; Hollenbeak, Christopher S; Leung, Anna M

2015-08-01

For elderly patients with early-stage breast cancer, the standards of care often are not strictly followed due to either clinician biases or patient preferences. The authors hypothesized that forgoing radiation and lymph node (LN) staging for elderly patients with early-stage breast cancer would have a negative impact on survival. From the Surveillance, Epidemiology, and End Results Program database, 53,619 women older than 55 years with stage 1 breast cancer who underwent breast conservation surgery were identified. Analyses were performed to compare the characteristics and outcomes of patients who received the standards of care with LN sampling and radiation and those of patients who did not, with control used for confounders. To account for selection bias from covariate imbalance, propensity score matching was performed. Survival was analyzed using the Kaplan-Meier method. Older patients were less likely to receive radiation and LN sampling. These standards of care were associated with improved overall survival rates of 15.8 and 27.1 % after 10 years, respectively (p ≤ 0.0001). This survival advantage persisted after propensity score matching, with a 7.4 % higher survival rate for patients who received radiation and a 16.8 % higher survival rate for those who underwent LN staging (p < 0.0001). Lymph node sampling and radiation therapy also conferred a statistically significant improvement in breast cancer-specific survival, with 1.3 and 2.6 % lower mortality rates respectively in the radiated and LN biopsy groups (p < 0.0001). As patients age, they are less likely to receive the standard of care for stage 1 breast cancer. Even after controlling for other factors, the study showed that failure to adhere to the standards of LN sampling and radiation therapy may have a negative impact in survival.

SK4 channels modulate Ca2+ signalling and cell cycle progression in murine breast cancer.

PubMed

Steudel, Friederike A; Mohr, Corinna J; Stegen, Benjamin; Nguyen, Hoang Y; Barnert, Andrea; Steinle, Marc; Beer-Hammer, Sandra; Koch, Pierre; Lo, Wing-Yee; Schroth, Werner; Hoppe, Reiner; Brauch, Hiltrud; Ruth, Peter; Huber, Stephan M; Lukowski, Robert

2017-09-01

Oncogenic signalling via Ca 2+ -activated K + channels of intermediate conductance (SK4, also known as K Ca 3.1 or IK) has been implicated in different cancer entities including breast cancer. Yet, the role of endogenous SK4 channels for tumorigenesis is unclear. Herein, we generated SK4-negative tumours by crossing SK4-deficient (SK4 KO) mice to the polyoma middle T-antigen (PyMT) and epidermal growth factor receptor 2 (cNeu) breast cancer models in which oncogene expression is driven by the retroviral promoter MMTV. Survival parameters and tumour progression were studied in cancer-prone SK4 KO in comparison with wild-type (WT) mice and in a syngeneic orthotopic mouse model following transplantation of SK4-negative or WT tumour cells. SK4 activity was modulated by genetic or pharmacological means using the SK4 inhibitor TRAM-34 in order to establish the role of breast tumour SK4 for cell growth, electrophysiological signalling, and [Ca 2+ ] i oscillations. Ablation of SK4 and TRAM-34 treatment reduced the SK4-generated current fraction, growth factor-dependent Ca 2+ entry, cell cycle progression and the proliferation rate of MMTV-PyMT tumour cells. In vivo, PyMT oncogene-driven tumorigenesis was only marginally affected by the global lack of SK4, whereas tumour progression was significantly delayed after orthotopic implantation of MMTV-PyMT SK4 KO breast tumour cells. However, overall survival and progression-free survival time in the MMTV-cNeu mouse model were significantly extended in the absence of SK4. Collectively, our data from murine breast cancer models indicate that SK4 activity is crucial for cell cycle control. Thus, the modulation of this channel should be further investigated towards a potential improvement of existing antitumour strategies in human breast cancer. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

MUC4 overexpression augments cell migration and metastasis through EGFR family proteins in triple negative breast cancer cells.

PubMed

Mukhopadhyay, Partha; Lakshmanan, Imayavaramban; Ponnusamy, Moorthy P; Chakraborty, Subhankar; Jain, Maneesh; Pai, Priya; Smith, Lynette M; Lele, Subodh M; Batra, Surinder K

2013-01-01

Current studies indicate that triple negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and an early pattern of metastasis. Emerging evidence suggests that MUC4 mucin is associated with metastasis of various cancers, including breast cancer. However, the functional role of MUC4 remains unclear in breast cancers, especially in TNBCs. In the present study, we investigated the functional and mechanistic roles of MUC4 in potentiating pathogenic signals including EGFR family proteins to promote TNBC aggressiveness using in vitro and in vivo studies. Further, we studied the expression of MUC4 in invasive TNBC tissue and normal breast tissue by immunostaining. MUC4 promotes proliferation, anchorage-dependent and-independent growth of TNBC cells, augments TNBC cell migratory and invasive potential in vitro, and enhances tumorigenicity and metastasis in vivo. In addition, our studies demonstrated that MUC4 up-regulates the EGFR family of proteins, and augments downstream Erk1/2, PKC-γ, and FAK mediated oncogenic signaling. Moreover, our studies also showed that knockdown of MUC4 in TNBC cells induced molecular changes suggestive of mesenchymal to epithelial transition. We also demonstrated in this study, for the first time, that knockdown of MUC4 was associated with reduced expression of EGFR and ErbB3 (EGFR family proteins) in TNBC cells, suggesting that MUC4 uses an alternative to ErbB2 mechanism to promote aggressiveness. We further demonstrate that MUC4 is differentially over-expressed in invasive TNBC tissues compared to normal breast tissue. MUC4 mucin expression is associated with TNBC pathobiology, and its knockdown reduced aggressiveness in vitro, and tumorigenesis and metastasis in vivo. Overall, our findings suggest that MUC4 mucin promotes invasive activities of TNBC cells by altering the expression of EGFR, ErbB2, and ErbB3 molecules and their downstream signaling.

Zoledronic Acid-Induced Expansion of γδ T Cells from Early-Stage Breast Cancer Patients: Effect of IL-18 on Helper NK Cells

PubMed Central

Sugie, Tomoharu; Murata-Hirai, Kaoru; Iwasaki, Masashi; Morita, Craig T.; Li, Wen; Okamura, Haruki; Minato, Nagahiro; Toi, Masakazu; Tanaka, Yoshimasa

2013-01-01

Human γδ T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. The responsiveness of Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2 T cells and helper NK cells from patients with either low or high frequencies of Vγ2Vδ2 T cells. Treatment of breast cancer patients with Zol alone decreased the number of Vγ2Vδ2 T cells and reduced their ex vivo responsiveness. These results demonstrate that Zol can elicit immunological responses by γδ T cells from early-stage breast cancer patients but that frequent in vivo treatment reduces Vγ2Vδ2 T cell numbers and their responsiveness to stimulation. PMID:23151944

Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion.

PubMed

Wolfe, Andy R; Ernlund, Amanda; McGuinness, William; Lehmann, Carl; Carl, Kaitlyn; Balmaceda, Nicole; Neufeld, Kristi L

2017-02-15

Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in a model organism. One such oncogene, Musashi-1 ( Msi-1 ), regulates translation of target mRNAs and is implicated in promoting tumorigenesis in the colon and other tissues. Msi-1 targets include the tumor suppressor adenomatous polyposis coli ( Apc ), a Wnt pathway antagonist lost in ∼80% of all colorectal cancers. Cell culture experiments have established that Msi-1 is a Wnt target, thus positioning Msi-1 and Apc as mutual antagonists in a mutually repressive feedback loop. Here, we report that intestines from mice lacking Msi-1 display aberrant Apc and Msi-1 mutually repressive feedback, reduced Wnt and Notch signaling, decreased proliferation, and changes in stem cell populations, features predicted to suppress tumorigenesis. Indeed, mice with germline Apc mutations ( Apc Min ) or with the Apc 1322T truncation mutation have a dramatic reduction in intestinal polyp number when Msi-1 is deleted. Taken together, these results provide genetic evidence that Msi-1 contributes to intestinal tumorigenesis driven by Apc loss, and validate the pursuit of Msi-1 inhibitors as chemo-prevention agents to reduce tumor burden. © 2017. Published by The Company of Biologists Ltd.

A quality improvement project to improve the rate of early breast milk expression in mothers of preterm infants.

PubMed

Murphy, Lindsey; Warner, Diane D; Parks, Jessica; Whitt, Jenny; Peter-Wohl, Sigal

2014-11-01

Providing breast milk is challenging for non-nursing mothers of premature infants. Early breast milk expression results in successful and longer lactation in mothers of very low birth weight (VLBW) infants. This quality improvement initiative sought to increase the rate of early milk expression in mothers of VLBW infants and increase the proportion of infants receiving maternal breast milk (MBM) at 28 days of age and at discharge. Phase 1 (n = 45) occurred between April 1, 2012, and August 31, 2012. Phase 2 (n = 58) occurred between September 1, 2012, and February 28, 2013. Pre-phase 2 actions included increased lactation consultant workforce, early lactation consultation, tracking of MBM supply, and physician education. Inborn infants < 1500 grams were eligible. Primary outcomes were the time of first maternal milk expression (TFME) and infant feeding type at 28 days of age and at discharge. The median TFME decreased from 9 (25th, 75th percentile; 6, 16) hours to 6 (5, 11) hours after implementation (P = .06). The proportion of infants receiving exclusive MBM at 28 days and at discharge was 64% and 74%, respectively (P = .40), and the proportion of infants receiving exclusive MBM at discharge increased from 37% to 59% (P = .046). In conclusion, a multidisciplinary initiative aimed at improving the rate of early milk expression was associated with more VLBW infants receiving exclusive MBM at discharge. © The Author(s) 2014.

Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis

PubMed Central

Teoh-Fitzgerald, ML; Fitzgerald, MP; Zhong, W; Askeland, RW; Domann, FE

2013-01-01

Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging

Knowledge of risk factors and early detection methods and practices towards breast cancer among nurses in Indira Gandhi Medical College, Shimla, Himachal Pradesh, India.

PubMed

Fotedar, Vikas; Seam, Rajeev K; Gupta, Manoj K; Gupta, Manish; Vats, Siddharth; Verma, Sunita

2013-01-01

Breast cancer is an increasing health problem in India. Screening for early detection should lead to a reduction in mortality from the disease. It is known that motivation by nurses influences uptake of screening methods by women. This study aimed to investigate knowledge of breast cancer risk factors and early detection methods and the practice of screening among nurses in Indira Gandhi Medical College, Shimla, Himachal Pradesh. A cross-sectional study was conducted using a self-administered questionnaire to assess the knowledge of breast cancer risk factors, early detection methods and practice of screening methods among 457 nurses working in an Indira Gandhi Medical College, Shimla-H.P. Chi square test, Data was analysed using SPSS version 16. Test of significance used was chi square test. The response rate of the study was 94.9%. The average knowledge of risk factors about breast cancer of the entire population is 49%. 10.5% of nurses had poor knowledge, 25.2% of the nurses had good knowledge, 45% had very good knowledge and 16.3% of the nurses had excellent knowledge about risk factors of breast cancer and early detection methods. The knowledge level was significantly higher among BSC nurses than nurses with Diploma. 54% of participants in this study reportedly practice BSE at least once every year. Less than one-third reported that they had CBE within the past one year. 7% ever had mammogram before this study. Results from this study suggest the frequent continuing medical education programmes on breast cancer at institutional level is desirable.

Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer.

PubMed

Kuo, Wen-Hong; Lin, Po-Han; Huang, Ai-Chu; Chien, Yin-Hsiu; Liu, Tsang-Pai; Lu, Yen-Shen; Bai, Li-Yuan; Sargeant, Aaron M; Lin, Ching-Hung; Cheng, Ann-Lii; Hsieh, Fon-Jou; Hwu, Wuh-Liang; Chang, King-Jen

2012-02-01

Although evidence suggests an importance of genetic factors in the development of breast cancer in Taiwanese (ethnic Chinese) women, including a high incidence of early-onset and secondary contralateral breast cancer, a major breast cancer predisposition gene, BRCA1, has not been well studied in this population. In fact, the carcinogenic impacts of many genetic variants of BRCA1 are unknown and classified as variants of uncertain significance (VUS). It is therefore important to establish a method to characterize the BRCA1 VUSs and understand their role in Taiwanese breast cancer patients. Accordingly, we developed a multimodel assessment strategy consisting of a prescreening portion and a validated functional assay to study breast cancer patients with early-onset, bilateral or familial breast cancer. We found germ-line BRCA1 mutations in 11.1% of our cohort and identified one novel missense mutation, c.5191C>A. Two genetic variants were initially classified as VUSs (c.1155C>T and c.5191C>A). c.1155C>T is not predicted to be deleterious in the prescreening portion of our assessment strategy. c.5191C>A, on the other hand, causes p.T1691K, which is predicted to have high deleterious probability because of significant structural alteration, a high deleterious score in the predictive programs and, clinically, triple negative characteristics in breast tumors. This mutant is confirmed by transcription activation and yeast growth-inhibition assays. In conclusion, we show as high a prevalence of germ-line BRCA1 mutation in high-risk Taiwanese patients as in Caucasians and demonstrate a useful strategy for studying BRCA1 VUSs.

Effect of marination on CIELAB L* values of early-deboned broiler breast meat depends on raw material color lightness

USDA-ARS?s Scientific Manuscript database

The objective was to evaluate the effect of vacuum-tumbling marination on CIELAB L* values of early-deboned broiler breast fillets (p. major) with different color lightness. Early deboned (2 h postmortem) broiler fillets were visually selected based on their color lightness from a commercial plant a...

Body Mass Index and Locoregional Recurrence in Women with Early-Stage Breast Cancer.

PubMed

Warren, Laura E G; Ligibel, Jennifer A; Chen, Yu-Hui; Truong, Linh; Catalano, Paul J; Bellon, Jennifer R

2016-11-01

Higher body mass index (BMI) has been associated with increased distant recurrence and decreased survival for women with breast cancer. However, the relationship between BMI and locoregional recurrence (LRR) has been less well studied and was therefore the subject of this investigation. The study identified 878 women with early-stage invasive breast cancer who underwent breast-conservation therapy (BCT) between June 1997 and October 2007. Time from diagnosis to LRR was calculated using a competing risk analysis with contralateral breast cancer (CBC), distant metastases (DM), and death as the competing risks. Gray's competing risks analysis, which included an interaction term between menopausal status and BMI, was used to identify significant risk factors for the development of LRR. After a median follow-up period of 10.8 years, LRR was diagnosed as a first event for 45 women. In a multivariable analysis, BMI was positively associated with LRR but only in premenopausal women. Specifically, when these women were compared with normal- and underweight women, both the overweight women (hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.04-8.46; p = 0.04) and the obese women (HR, 3.36; 95 % CI 1.07-10.63; p = 0.04) showed a higher risk of LRR. A similar association between BMI and disease-free survival was noted for premenopausal but not postmenopausal women. For premenopausal women with invasive breast cancer who undergo BCT, BMI is an independent prognostic factor for LRR. If confirmed, these findings suggest that more aggressive treatment strategies may be warranted for these women.

Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

PubMed

Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

2002-10-15

Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism

PubMed Central

Castagnet, Patrice; Chemlali, Walid; Lallemand, François; Meseure, Didier; Pocard, Marc; Bieche, Ivan; Perrot-Applanat, Martine

2018-01-01

Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP). The aim of this study was to identify the type of breast tumors (ERα-positive or ERα-negative) that express AHR and how AhR affects human tumorigenesis. The levels of AHR, AHR nuclear translocator (ARNT) and AHR repressor (AHRR) mRNA expression were analyzed in a cohort of 439 breast tumors, demonstrating a weak association between high AHR expression and age greater than fifty years and ERα-negative status, and HR-/ERBB2 breast cancer subtypes. AHRR mRNA expression was associated with metastasis-free survival, while AHR mRNA expression was not. Immunohistochemistry revealed the presence of AhR protein in both tumor cells (nucleus and/or cytoplasm) and the tumor microenvironment (including endothelial cells and lymphocytes). High AHR expression was correlated with high expression of several genes involved in signaling pathways related to inflammation (IL1B, IL6, TNF, IL8 and CXCR4), metabolism (IDO1 and TDO2 from the kynurenine pathway), invasion (MMP1, MMP2 and PLAU), and IGF signaling (IGF2R, IGF1R and TGFB1). Two well-known ligands for AHR (TCDD and BaP) induced mRNA expression of IL1B and IL6 in an ERα-negative breast tumor cell line. The breast cancer ER status likely influences AhR activity involved in these signaling pathways. The mechanisms involved in AhR activation and target gene expression in breast cancers are also discussed. PMID:29320557

High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism.

PubMed

Vacher, Sophie; Castagnet, Patrice; Chemlali, Walid; Lallemand, François; Meseure, Didier; Pocard, Marc; Bieche, Ivan; Perrot-Applanat, Martine

2018-01-01

Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP). The aim of this study was to identify the type of breast tumors (ERα-positive or ERα-negative) that express AHR and how AhR affects human tumorigenesis. The levels of AHR, AHR nuclear translocator (ARNT) and AHR repressor (AHRR) mRNA expression were analyzed in a cohort of 439 breast tumors, demonstrating a weak association between high AHR expression and age greater than fifty years and ERα-negative status, and HR-/ERBB2 breast cancer subtypes. AHRR mRNA expression was associated with metastasis-free survival, while AHR mRNA expression was not. Immunohistochemistry revealed the presence of AhR protein in both tumor cells (nucleus and/or cytoplasm) and the tumor microenvironment (including endothelial cells and lymphocytes). High AHR expression was correlated with high expression of several genes involved in signaling pathways related to inflammation (IL1B, IL6, TNF, IL8 and CXCR4), metabolism (IDO1 and TDO2 from the kynurenine pathway), invasion (MMP1, MMP2 and PLAU), and IGF signaling (IGF2R, IGF1R and TGFB1). Two well-known ligands for AHR (TCDD and BaP) induced mRNA expression of IL1B and IL6 in an ERα-negative breast tumor cell line. The breast cancer ER status likely influences AhR activity involved in these signaling pathways. The mechanisms involved in AhR activation and target gene expression in breast cancers are also discussed.

Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

PubMed

Ashrafian, Houman; O'Flaherty, Linda; Adam, Julie; Steeples, Violetta; Chung, Yuen-Li; East, Phil; Vanharanta, Sakari; Lehtonen, Heli; Nye, Emma; Hatipoglu, Emine; Miranda, Melroy; Howarth, Kimberley; Shukla, Deepa; Troy, Helen; Griffiths, John; Spencer-Dene, Bradley; Yusuf, Mohammed; Volpi, Emanuela; Maxwell, Patrick H; Stamp, Gordon; Poulsom, Richard; Pugh, Christopher W; Costa, Barbara; Bardella, Chiara; Di Renzo, Maria Flavia; Kotlikoff, Michael I; Launonen, Virpi; Aaltonen, Lauri; El-Bahrawy, Mona; Tomlinson, Ian; Pollard, Patrick J

2010-11-15

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. Copyright © 2010 AACR.

Chromosome 3p allele loss in early invasive breast cancer: detailed mapping and association with clinicopathological features

PubMed Central

Martinez, A; Walker, R A; Shaw, J A; Dearing, S J; Maher, E R; Latif, F

2001-01-01

Aims—Chromosome 3p allele loss is a frequent event in many common sporadic cancers including lung, breast, kidney, ovarian, and head and neck cancer. To analyse the extent and frequency of 3p allelic losses in T1N0 and T1N1 invasive sporadic breast cancer, 19 microsatellite markers spread along 3p were analysed in 40 such breast carcinomas with known clinicopathological parameters. Methods—Loss of heterozygosity analysis was carried out using 3p microsatellite markers that were non-randomly distributed and chosen to represent regions that show hemizygous and/or homozygous losses in lung cancer (lung cancer tumour suppressor gene region 1 ( LCTSGR1) at 3p21.3 and LCTSGR2 at 3p12), and regions demonstrating suppression of tumorigenicity in breast, kidney, lung, and ovarian cancer. Results—Allelic loss was seen at one or more loci in 22 of these clinically early stage sporadic breast tumours, but none had complete 3p allele loss. Several regions with non-overlapping deletions were defined, namely: (1) 18 tumours showed loss at 3p21–22, a physical distance of 12 Mb; (2) 11 tumours showed loss at 3p12 within a physical distance of 1 Mb, this region is contained within LCTSGR2; (3) six tumours showed loss at 3p25–24, including the von Hippel-Lindau (VHL) locus; (4) five tumours showed loss at 3p14.2, including the fragile histidine triad (FHIT) locus. Conclusions—This is the largest study to date defining the extent and range of 3p allelic losses in early stage invasive breast cancer and the results indicate that region 3p21–22 containing LCTSGR1 and a region at 3p12 within LCTSGR2 are the most frequent sites of 3p allelic loss in these breast carcinomas. This suggests that tumour suppressor genes located in these regions may play important roles in the development of breast cancer. There was an association between increasing 3p allelic loss and increasing tumour grade and loss of progesterone (p = 0.0098) and oestrogen (p = 0.0472) receptor expression

Chromosome 3p allele loss in early invasive breast cancer: detailed mapping and association with clinicopathological features.

PubMed

Martinez, A; Walker, R A; Shaw, J A; Dearing, S J; Maher, E R; Latif, F

2001-10-01

Chromosome 3p allele loss is a frequent event in many common sporadic cancers including lung, breast, kidney, ovarian, and head and neck cancer. To analyse the extent and frequency of 3p allelic losses in T1N0 and T1N1 invasive sporadic breast cancer, 19 microsatellite markers spread along 3p were analysed in 40 such breast carcinomas with known clinicopathological parameters. Loss of heterozygosity analysis was carried out using 3p microsatellite markers that were non-randomly distributed and chosen to represent regions that show hemizygous and/or homozygous losses in lung cancer (lung cancer tumour suppressor gene region 1 ( LCTSGR1) at 3p21.3 and LCTSGR2 at 3p12), and regions demonstrating suppression of tumorigenicity in breast, kidney, lung, and ovarian cancer. Allelic loss was seen at one or more loci in 22 of these clinically early stage sporadic breast tumours, but none had complete 3p allele loss. Several regions with non-overlapping deletions were defined, namely: (1) 18 tumours showed loss at 3p21-22, a physical distance of 12 Mb; (2) 11 tumours showed loss at 3p12 within a physical distance of 1 Mb, this region is contained within LCTSGR2; (3) six tumours showed loss at 3p25-24, including the von Hippel-Lindau (VHL) locus; (4) five tumours showed loss at 3p14.2, including the fragile histidine triad (FHIT) locus. This is the largest study to date defining the extent and range of 3p allelic losses in early stage invasive breast cancer and the results indicate that region 3p21-22 containing LCTSGR1 and a region at 3p12 within LCTSGR2 are the most frequent sites of 3p allelic loss in these breast carcinomas. This suggests that tumour suppressor genes located in these regions may play important roles in the development of breast cancer. There was an association between increasing 3p allelic loss and increasing tumour grade and loss of progesterone (p = 0.0098) and oestrogen (p = 0.0472) receptor expression, indicating a link between 3p allelic loss and the

Targeting the androgen receptor in triple-negative breast cancer: current perspectives.

PubMed

Mina, Alain; Yoder, Rachel; Sharma, Priyanka

2017-01-01

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR) signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition.

Outpatient follow-up after treatment for early breast cancer: updated results after 5 years.

PubMed

Churn, M; Kelly, V

2001-01-01

The value of frequent outpatient follow-up in the first few years after primary treatment for early breast cancer is a controversial issue. Schedules involving 3-4 monthly visits in the first 2-3 years and 6-monthly from years 3-5 are still commonplace. In this study we audited such a policy from a single cancer centre, identifying a cohort of all 612 patients with early breast cancer (pT(1-3)pN(0-1)NxM0) referred for adjuvant therapy in 1993. The hospital records were reviewed to ascertain patient and tumour characteristics, the surgical and adjuvant treatment received, the timing and sequencing of recurrences and their mode of detection. Five hundred and five patients had breast conservation surgery. The actuarial local recurrence-free survival rate at 5 years in this group was 94.5%. Twenty-five of the 31 local recurrences that occurred were the first site of relapse. Eight (32%) of these were detected at routine clinic appointments, seven (28%) by routine mammography, and nine (36%) were interim referrals. Significant risk factors for local recurrence identified were lymph node status (P = 0.03) and tumour grade (P = 0.04). One hundred and four patients underwent mastectomy. The actuarial local recurrence-free survival at 5 years in this group was 85.4%. Nine of the 13 local recurrences were the first site of relapse. Six (66.7%) of these were detected at routine appointments. The significant risk factor for local recurrence identified was tumour grade (P = 0.03). Overall, 60.1% of metastases presented as interim referrals. Nodal status, tumour grade and tumour stage were confirmed as significant risk factors for metastasis (P < or = 0.001). Hazard rate analysis demonstrated a peak incidence of both local and metastatic recurrences in the second year, diminishing thereafter. This peak was largely confined to patients with tumours with poor prognostic features. We identified only eight patients out of a total of 612 followed up as outpatients for 5 years who had

Ras-Directed N-Glycoproteins Are Novel Early Biomarkers for Tumorigenesis and Malignant Transformation and Therapeutic Targets of Neurofibromatosis Type 1

DTIC Science & Technology

2014-08-01

phosphorylates Ser192 in MGAT5B in MPNST cells. Moreover, wild type MGAT5B protein locates in the Golgi apparatus whereas mutated MGAT5BS192A protein...to the Golgi apparatus to attenuate MGAT5B-mediated glycosylation and phosphorylation of kinase receptors. Targeting MGAT5-mediated glycosylation of...tumorigenesis in Nf1+/-;p53+/- mice (bottom). Because proteins travelling to the Golgi apparatus for the consequent steps of glycosylation must be

Human small breast epithelial mucin: the promise of a new breast tumor biomarker.

PubMed

Hubé, F; Mutawe, M; Leygue, E; Myal, Y

2004-12-01

Breast cancer remains one of the most frequently diagnosed cancers today. In developed countries, one in eight women is expected to present with breast cancer within her lifetime and an estimated 1,000,000 cases are detected each year worldwide (Canadian Cancer Statistics, http://www.cancer.ca/vgn/images/ portal/cit_86751114/14/33/1959864 11niw_stats2004_en.pdf). For women with recurrent disease, the median time of survival is about 2 years. Despite optimal surgery, adjuvant irradiation, hormonal treatment, and chemotherapy, approximately 30% of patients with localized breast cancer finally develop distant metastases. Early detection, which enables intervention at a localized and potentially curable stage, remains a central goal in breast cancer treatment. Indeed, the 5-year survival rate for women with breast cancer has been shown to increase dramatically when the disease is diagnosed at an early stage: from less than 25% in women with disseminated cancer to about 75% in patients with regional disease and over 95% in women with a localized tumor (Breast Cancer Facts and Figures, 2001-2002, http://www.cancer.org/downloads/STT/BrCaFF 2001.pdf). Unfortunately, only 60% of all breast cancers are diagnosed at a local stage. Any improvement in early detection through identification of tumor biomarkers would have a significant impact on reducing overall breast cancer mortality.

Endocrine Disruptors and the Breast: Early Life Effects and Later Life Disease

PubMed Central

Macon, Madisa B.

2013-01-01

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5–27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future. PMID:23417729

Endocrine disruptors and the breast: early life effects and later life disease.

PubMed

Macon, Madisa B; Fenton, Suzanne E

2013-03-01

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5-27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future.

Non-metabolic functions of glycolytic enzymes in tumorigenesis.

PubMed

Yu, X; Li, S

2017-05-11

Cancer cells reprogram their metabolism to meet the requirement for survival and rapid growth. One hallmark of cancer metabolism is elevated aerobic glycolysis and reduced oxidative phosphorylation. Emerging evidence showed that most glycolytic enzymes are deregulated in cancer cells and play important roles in tumorigenesis. Recent studies revealed that all essential glycolytic enzymes can be translocated into nucleus where they participate in tumor progression independent of their canonical metabolic roles. These noncanonical functions include anti-apoptosis, regulation of epigenetic modifications, modulation of transcription factors and co-factors, extracellular cytokine, protein kinase activity and mTORC1 signaling pathway, suggesting that these multifaceted glycolytic enzymes not only function in canonical metabolism but also directly link metabolism to epigenetic and transcription programs implicated in tumorigenesis. These findings underscore our understanding about how tumor cells adapt to nutrient and fuel availability in the environment and most importantly, provide insights into development of cancer therapy.

Breast Cancer—Patient Version

Cancer.gov

Breast cancer is the second most common cancer in women after skin cancer. Mammograms can detect breast cancer early, possibly before it has spread. Start here to find information on breast cancer treatment, causes and prevention, screening, research, and statistics.

Is the Macronutrient Intake of Formula-Fed Infants Greater Than Breast-Fed Infants in Early Infancy?

PubMed Central

Hester, Shelly N.; Hustead, Deborah S.; Mackey, Amy D.; Singhal, Atul; Marriage, Barbara J.

2012-01-01

Faster weight gain early in infancy may contribute to a greater risk of later obesity in formula-fed compared to breast-fed infants. One potential explanation for the difference in weight gain is higher macronutrient intake in formula-fed infants during the first weeks of life. A systematic review was conducted using Medline to assess the macronutrient and energy content plus volume of intake in breast-fed and formula-fed infants in early infancy. All studies from healthy, term, singleton infants reporting values for the composition of breast milk during the first month of life were included. The energy content of colostrum (mean, SEM: 53.6 ± 2.5 kcal/100 mL), transitional milk (57.7 ± 4.2 kcal/100 mL), and mature milk (65.2 ± 1.1 kcal/100 mL) was lower than conventional infant formula (67 kcal/100 mL) on all days analyzed. The protein concentration of colostrum (2.5 ± 0.2 g/100 mL) and transitional milk (1.7 ± 0.1 g/100 mL) was higher than formula (1.4 g/100 mL), while the protein content of mature milk (1.3 ± 0.1 g/100 mL) was slightly lower. Formula-fed infants consume a higher volume and more energy dense milk in early life leading to faster growth which could potentially program a greater risk of long-term obesity. PMID:23056929

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression in Genetically Hyper-Muscular Mice

DTIC Science & Technology

2007-07-01

preserve muscle in the end-stages of cancer, cancer cachexia . Up to 25% of breast cancer deaths may be attributed to muscle wasting from the complex... cachexia . 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin, MPA, DMBA, Activin receptor, cachexia . 16. SECURITY CLASSIFICATION OF: 17...progress, we turned to another question relating skeletal muscle and cancer—pathological muscle wasting in cancer cachexia . (6) (7) (8) Cancer cachexia

Influence of primary care professionals on early detection of breast cancer: different perception between family physicians and nursing professionals.

PubMed

Esteban-Vasallo, María D; Aerny-Perreten, Nicole; García-Riolobos, Carmen; López Rubio, Aranzazu; Domínguez-Berjón, Felicitas

2017-01-01

The aim of this study was to assess the level of self-perceived influence on early detection of breast cancer among nurses and family physicians (FP) working in primary care and to identify the factors associated with a lower perception in each group. In the Autonomous Community of Madrid, an online questionnaire on cancer prevention was sent to a random sample of primary care professionals (3586 FP and nurses). The data included sex, age, profession, years in primary care, specific postgraduate training, and opinions and attitudes toward cancer prevention. A descriptive analysis was carried out. Factors associated with a low/null self-perceived influence on early detection of breast cancer were analyzed separately for FP and nurses with multivariate logistic regression models. In all, 76.4% of the participants considered that their influence on the early detection of breast cancer was enough/high. FP attributed to themselves a higher influence than nurses (enough/high: 86.0 vs. 64.6%, P<0.01), and a lower perception was associated with a low/null perceived utility of their individual intervention [odds ratio (OR): 6.42, 95% confidence interval (CI) 2.77-14.85]. Among nurses, also associated with this low/null perceived utility [adjusted odds ratio (aOR): 2.81, 95% CI 1.37-5.77] were the absence of postgraduate training in the matter (aOR: 2.56, 95% CI 1.05-6.25), and a low/null perception of feasibility of prevention programs in their centers (aOR: 1.93, 95% CI 1.25-2.98). Primary care professionals perceive their activity in the early detection of breast cancer as relevant, especially FP. To increase knowledge of the utility of individual interventions, specific training and improvement of the feasibility of these programs could enhance this perception.

Relationship between preoperative breast MRI and surgical treatment of non-metastatic breast cancer.

PubMed

Onega, Tracy; Weiss, Julie E; Goodrich, Martha E; Zhu, Weiwei; DeMartini, Wendy B; Kerlikowske, Karla; Ozanne, Elissa; Tosteson, Anna N A; Henderson, Louise M; Buist, Diana S M; Wernli, Karen J; Herschorn, Sally D; Hotaling, Elise; O'Donoghue, Cristina; Hubbard, Rebecca

2017-12-01

More extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established. Using Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non-metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation). Clinical and sociodemographic covariates were included in multivariable logistic regression models to estimate adjusted odds ratios and 95% confidence intervals. Of the 13 097 women, 2217 (16.9%) had a preoperative MRI. Among the women with MRI, results indicated 32% higher odds of unilateral mastectomy compared to breast conserving surgery and of mastectomy with CPM compared to unilateral mastectomy. Women with preoperative MRI also had 56% higher odds of reconstruction. Preoperative MRI in women with DCIS and early stage invasive breast cancer is associated with more frequent mastectomy, CPM, and reconstruction surgical treatment. Use of more extensive surgical treatment and reconstruction among women with DCIS and early stage invasive cancer whom undergo MRI warrants further investigation. © 2017 Wiley Periodicals, Inc.

Effect of three postmortem electrical stimulation treatments on the quality of early-deboned broiler breast meat

USDA-ARS?s Scientific Manuscript database

Electrical stimulation (ES) of animal carcasses during postmortem has been commonly used by beef industry to enhance meat tenderness, and has been recently adapted for commercial use with poultry. Majority of published investigations of ES effects on the tenderness of early-deboned poultry breast m...

Optimized smith waterman processor design for breast cancer early diagnosis

NASA Astrophysics Data System (ADS)

Nurdin, D. S.; Isa, M. N.; Ismail, R. C.; Ahmad, M. I.

2017-09-01

This paper presents an optimized design of Processing Element (PE) of Systolic Array (SA) which implements affine gap penalty Smith Waterman (SW) algorithm on the Xilinx Virtex-6 XC6VLX75T Field Programmable Gate Array (FPGA) for Deoxyribonucleic Acid (DNA) sequence alignment. The PE optimization aims to reduce PE logic resources to increase number of PEs in FPGA for higher degree of parallelism during alignment matrix computations. This is useful for aligning long DNA-based disease sequence such as Breast Cancer (BC) for early diagnosis. The optimized PE architecture has the smallest PE area with 15 slices in a PE and 776 PEs implemented in the Virtex - 6 FPGA.

Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

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

Ma, Qing; Yu, Tao; Ren, Yao-Yao

2014-11-07

Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 ismore » down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.« less

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

PubMed

Sugishita, Mihoko; Imai, Tsuneo; Kikumori, Toyone; Mitsuma, Ayako; Shimokata, Tomoya; Shibata, Takashi; Morita, Sachi; Inada-Inoue, Megumi; Sawaki, Masataka; Hasegawa, Yoshinori; Ando, Yuichi

2016-03-01

Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

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

Zhi, Xiuyi; Giroux-Leprieur, Etienne; Respiratory Diseases and Thoracic Oncology Department, Ambroise Pare Hospital – APHP, Versailles Saint Quentin en Yvelines University, 9 Avenue Charles de Gaulle, 92100, Boulogne-Billancourt

2015-10-02

Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studiesmore » indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.« less

A proven and highly cost-effective method of early detection of breast cancer for developing countries.

PubMed

Rebentisch, D P; Rebentisch, H D; Thomas, K; Karat, S; Jadhav, A J

1995-12-01

Carcinoma of the breast is the third most common cancer in Indian women. With rapid industrialization and effective control of communicable diseases, better diagnostic and treatment facilities, cancer is emerging as a major health problem. Since early detection is the only way to reduce morbidity and mortality from breast cancer, we undertook a pilot project to evaluate efficacy of using existing manpower and resources for screening women in the high risk group. Methodology pros and cons, results, and recommendations are presented. Our method can be adopted by any developing country interested in a screening programme for malignant disease.

SUMOylated MAFB promotes colorectal cancer tumorigenesis

PubMed Central

Xie, Yin-Yin; Sun, Xiao-Jian; Zhao, Ren; Huang, Qiu-Hua

2016-01-01

The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro. We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment. PMID:27829226

Unraveling the Molecular Mechanism(s) Underlying ER+/PR- Breast Tumorigenesis Using a Novel Genetically Engineered Mouse Model

DTIC Science & Technology

2010-09-01

Gria4 Glutamate receptor ionotropic , AMPA 4 NM_019691 transport ion transport 3.00 Slc2a1 solute carrier family 2,member 1 NM_011400...unlimited 13. SUPPLEMENTARY NOTES 14. A BSTRACT Estrogen-rece ptor alpha (E Rα)-positive Progesterone receptor ne gative (ER+ /PR-) breast ductal...fo r t reating ER+/PR- breast cancers that are resistant to tamoxifen or trastuzumab. 15. SUBJECT TERMS Estrogen receptor , Progesterone receptor

Genomic Copy Number Imbalances Associated with Bone and Non-bone Metastasis of Early-Stage Breast Cancer

PubMed Central

Liu, Yanhong; Zhou, Renke; Baumbusch, Lars O.; Tsavachidis, Spyros; Brewster, Abenaa M.; Do, Kim-Anh; Sahin, Aysegul; Hortobagyi, Gabriel N.; Taube, Joseph H.; Mani, Sendurai A.; Aarøe, Jørgen; Wärnberg, Fredrik; Børresen-Dale, Anne-Lise; Mills, Gordon B.; Thompson, Patricia A.; Bondy, Melissa L.

2014-01-01

Purpose To identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Patients and Methods Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Results Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3–22.2, 3q27.1, 10q23.1, and 14q13.2–3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios (HRs). For bone metastasis, the hazard (95% confidence interval) for the low-risk group was 0.32 (0.11–0.92) compared to the intermediate-risk group and 2.99 (1.74–5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17–0.66) and 2.33 (1.59–3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Conclusions Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk. PMID:24305980

Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer.

PubMed Central

Siegel, P M; Ryan, E D; Cardiff, R D; Muller, W J

1999-01-01

To assess the importance of Neu activation during mammary tumorigenesis, altered receptors harboring in-frame deletions within the extracellular domain were expressed in transgenic mice. Females from several independent lines develop multiple mammary tumors that frequently metastasize to the lung. Tumor progression in these strains was associated with elevated levels of tyrosine-phosphorylated Neu and ErbB-3. Consistent with these observations, a survey of primary human breast tumors revealed frequent co-expression of both erbB-2 and erbB-3 transcripts. The ability of altered Neu receptors to induce mammary tumorigenesis in transgenic mice prompted us to examine whether similar mutations occurred in ErbB-2 during human breast cancer progression. Interestingly, an alternatively spliced form of erbB-2, closely resembling spontaneous activated forms of neu, was detected in human breast tumors. The ErbB-2 receptor encoded by this novel transcript harbors an in-frame deletion of 16 amino acids in the extracellular domain and can transform Rat-1 fibroblasts. Together, these observations argue that co-expression of ErbB-2 and ErbB-3 may play a critical role in the induction of human breast tumors, and raise the possibility that activating mutations in the ErbB-2 receptor may also contribute to this process. PMID:10205169

The connection between the breast and heart in a woman: Breast cancer and cardiovascular disease.

PubMed

Gulati, Martha; Mulvagh, Sharon L

2018-02-01

Cardiovascular disease remains the leading cause of death in women in the United States and is a major public health issue for all women, but it is of increasing concern to breast cancer survivors. Advancements in early detection and breast cancer therapy have resulted in over 90% of women surviving 5 years past their diagnosis of breast cancer. Nonetheless, with increased survivorship from breast cancer, there has been an increase in cardiovascular disease in these women. The consequences of the treatments for breast cancer may increase the risk for cardiovascular disease. Additionally, there is an overlap of risk factors common to both breast cancer and cardiovascular disease. The increased risk of cardiovascular disease in women who survive breast cancer must be recognized, with a focus on the prevention and early detection of cardiovascular disease. © 2018 Wiley Periodicals, Inc.

Adducin in tumorigenesis and metastasis.

PubMed

Luo, Cong; Shen, Jiayu

2017-07-18

Adducin is a membrane-skeletal protein localized at spectrin-actin junctions, involving in the formation of the network of cytoskeleton, cellular signal transduction, ionic transportation, cell motility and cell proliferation. While previous researches focused mainly on the relationship between adducin and hypertension, there are few studies focusing on the role of adducin in tumor. Previous studies showed that adducin played a role in the evolution and progression of neoplasm. This review makes a brief summary on the structure, function and mechanism of adducin and how adducin functions in tumorigenesis and metastasis.

Proteomics analysis of human breast milk to assess breast cancer risk.

PubMed

Aslebagh, Roshanak; Channaveerappa, Devika; Arcaro, Kathleen F; Darie, Costel C

2018-02-01

Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from eight women provided five paired-groups (cancer versus control) for analysis of dysregulatedproteins: two within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and three across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the five comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research. Data are available via ProteomeXchange with identifier

75 FR 57472 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC): Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC): Notice of Charter Renewal This gives notice under the Federal Advisory Committee Act (Pub. L. 92-463) of October 6, 1972, that the...

Couples' Support-Related Communication, Psychological Distress, and Relationship Satisfaction among Women with Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon; Sherman, Marne; Ross, Stephanie; Ostroff, Jamie; Heyman, Richard E.; Fox, Kevin

2004-01-01

This study examined associations between couple communication about cancer and psychological distress and relationship satisfaction of women diagnosed with early stage breast cancer. One hundred forty-eight couples completed a videotaped discussion of a cancer-related issue and a general issue. Patients completed measures of psychological distress…

PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

PubMed

Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

2018-03-12

The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Barriers to early diagnosis of symptomatic breast cancer: a qualitative study of Black African, Black Caribbean and White British women living in the UK.

PubMed

Jones, Claire E L; Maben, Jill; Lucas, Grace; Davies, Elizabeth A; Jack, Ruth H; Ream, Emma

2015-03-13

Understanding barriers to early diagnosis of symptomatic breast cancer among Black African, Black Caribbean and White British women in the UK. In-depth qualitative interviews using grounded theory methods to identify themes. Findings validated through focus groups. 94 women aged 33-91 years; 20 Black African, 20 Black Caribbean and 20 White British women diagnosed with symptomatic breast cancer were interviewed. Fourteen Black African and 20 Black Caribbean women with (n=19) and without (n=15) breast cancer participated in six focus groups. Eight cancer centres/hospital trusts in London (n=5), Somerset (n=1), West Midlands (n=1) and Greater Manchester (n=1) during 2012-2013. There are important differences and similarities in barriers to early diagnosis of breast cancer between Black African, Black Caribbean and White British women in the UK. Differences were influenced by country of birth, time spent in UK and age. First generation Black African women experienced most barriers and longest delays. Second generation Black Caribbean and White British women were similar and experienced fewest barriers. Absence of pain was a barrier for Black African and Black Caribbean women. Older White British women (≥70 years) and first generation Black African and Black Caribbean women shared conservative attitudes and taboos about breast awareness. All women viewed themselves at low risk of the disease, and voiced uncertainty over breast awareness and appraising non-lump symptoms. Focus group findings validated and expanded themes identified in interviews. Findings challenged reporting of Black women homogenously in breast cancer research. This can mask distinctions within and between ethnic groups. Current media and health promotion messages need reframing to promote early presentation with breast symptoms. Working with communities and developing culturally appropriate materials may lessen taboos and stigma, raise awareness, increase discussion of breast cancer and promote

Barriers to early diagnosis of symptomatic breast cancer: a qualitative study of Black African, Black Caribbean and White British women living in the UK

PubMed Central

Jones, Claire E L; Maben, Jill; Lucas, Grace; Davies, Elizabeth A; Jack, Ruth H; Ream, Emma

2015-01-01

Objectives Understanding barriers to early diagnosis of symptomatic breast cancer among Black African, Black Caribbean and White British women in the UK. Design In-depth qualitative interviews using grounded theory methods to identify themes. Findings validated through focus groups. Participants 94 women aged 33–91 years; 20 Black African, 20 Black Caribbean and 20 White British women diagnosed with symptomatic breast cancer were interviewed. Fourteen Black African and 20 Black Caribbean women with (n=19) and without (n=15) breast cancer participated in six focus groups. Setting Eight cancer centres/hospital trusts in London (n=5), Somerset (n=1), West Midlands (n=1) and Greater Manchester (n=1) during 2012–2013. Results There are important differences and similarities in barriers to early diagnosis of breast cancer between Black African, Black Caribbean and White British women in the UK. Differences were influenced by country of birth, time spent in UK and age. First generation Black African women experienced most barriers and longest delays. Second generation Black Caribbean and White British women were similar and experienced fewest barriers. Absence of pain was a barrier for Black African and Black Caribbean women. Older White British women (≥70 years) and first generation Black African and Black Caribbean women shared conservative attitudes and taboos about breast awareness. All women viewed themselves at low risk of the disease, and voiced uncertainty over breast awareness and appraising non-lump symptoms. Focus group findings validated and expanded themes identified in interviews. Conclusions Findings challenged reporting of Black women homogenously in breast cancer research. This can mask distinctions within and between ethnic groups. Current media and health promotion messages need reframing to promote early presentation with breast symptoms. Working with communities and developing culturally appropriate materials may lessen taboos and stigma

Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

PubMed

Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena

2014-10-15

The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens.

PubMed Central

Chen, J D; Van Dyke, T

1991-01-01

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis. Images PMID:1658622

Information Needs of Older Women With Early-Stage Breast Cancer When Making Radiation Therapy Decisions.

PubMed

Wang, Shi-Yi; Kelly, Gabrielle; Gross, Cary; Killelea, Brigid K; Mougalian, Sarah; Presley, Carolyn; Fraenkel, Liana; Evans, Suzanne B

2017-07-15

To identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decision maker. We surveyed (through face-to-face interview, telephone, or mail) women aged ≥65 years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker. The response rate was 56.4% (93 of 165). Mean age was 72.5 years, ranging from 65 to 93 years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75 years rated 13.9 questions as essential, whereas participants aged ≤74 years rated 18.7 as essential (P=.018). Older women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants. Copyright © 2017 Elsevier Inc. All rights reserved.