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

ClinicalTrials.gov

2017-08-01

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

Breast Cancer Epidemiology in Puerto Rico

DTIC Science & Technology

2014-08-01

April 20: a. Poster: Effects of herbal enzyme bromelain against breast cancer cell line. Paroulek, Jaffe and Rathinavelu. Nova Southeastern Univ. 3...Canada. ii. American College of Sports Medicine 2009 in Seattle, Washington (May 27-30) 4. Thursday, May 28: a. Session: Exercise interventions in...Clinical Medicine II – Medical i. Effect of comprehensive exercise on lymphedema in breast cancer survivors: a pilot study. Oki, Troumbley, Walker

Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

ClinicalTrials.gov

2018-05-25

Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-06-28

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

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

ClinicalTrials.gov

2017-06-14

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

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

ClinicalTrials.gov

2017-08-07

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

Loss of LRIG1 locus increases risk of early and late relapse of stage I/II breast cancer.

PubMed

Thompson, Patricia A; Ljuslinder, Ingrid; Tsavachidis, Spyros; Brewster, Abenaa; Sahin, Aysegul; Hedman, Håkan; Henriksson, Roger; Bondy, Melissa L; Melin, Beatrice S

2014-06-01

Gains and losses at chromosome 3p12-21 are common in breast tumors and associated with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose product functions in ErbB-family member degradation, is a critical tumor modifier at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan molecular inversion probe arrays that include 12 probes located within LRIG1. Copy number results were validated against gene expression data available in the public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm a breakpoint in the gene and show that gains and losses in the subregions differ by tumor and patient characteristics including race/ethnicity. In analyses adjusted for known prognostic factors, loss of LRIG1 was independently associated with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse≥5 years (HR, 2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of copy number across chromosome 3, as well as expression data from pooled, publicly available datasets, corroborated the hypothesis of an elevated and persistent risk among cases with loss of or low LRIG1. We concluded that loss/low expression of LRIG1 is an independent risk factor for breast cancer metastasis and death in stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor of tumor metastasis and is an early clinical indicator of risk for late recurrences in otherwise low-risk patients. ©2014 American Association for Cancer Research.

Polymorphic CA repeats in the IGF-I gene and breast cancer.

PubMed

Yu, H; Li, B D; Smith, M; Shi, R; Berkel, H J; Kato, I

2001-11-01

Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16-7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42-18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.

Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review.

PubMed

Cabarrou, B; Mourey, L; Dalenc, F; Balardy, L; Kanoun, D; Roché, H; Boher, J M; Rougé-Bugat, M E; Filleron, Thomas

2017-08-01

As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

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

ClinicalTrials.gov

2018-05-01

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

Specific activity of class II histone deacetylases in human breast cancer cells

PubMed Central

Duong, Vanessa; Bret, Caroline; Altucci, Lucia; Mai, Antonello; Duraffourd, Céline; Loubersac, Julie; Harmand, Pierre-Olivier; Bonnet, Sandrine; Valente, Sergio; Maudelonde, Thierry; Cavailles, Vincent; Boulle, Nathalie

2008-01-01

Although numerous studies have underlined the role of HDACs in breast physiology and tumorigenesis, little is known on the particular contribution of the various classes of HDACs in these processes. Using ERα-positive MCF-7 breast cancer cells, the effects of MC1575 and MC1568, two novel class II specific HDAC inhibitors (HDI), were analyzed on cell proliferation, apoptosis and estrogen signalling. The specificity of these HDIs was validated by measuring histone and α-tubulin acetylation and by the specific in vitro inhibition of recombinant HDAC4 using histone and non histone substrates, contrasting with the lack of inhibition of class I HDACs. In addition, MC1575 did not inhibit class I HDAC gene expression thus confirming the specific targeting of class II enzymes. Similar to TSA, MC1575 displayed a dose-dependent anti-proliferative effect and induced cell cycle arrest although this blockade occurred at a different level than TSA. Moreover, and in contrast to TSA, MC1575 had no effect on MCF-7 cells apoptosis. Interestingly, MC1575 was able to increase p2lwaf1/CIP1 mRNA levels but did not regulate the expression of other genes such as cyclin D1, p27, p14ARF, Bcl2, Baxα, Trail-R1 and -R2. Finally, MC1575 strongly induced ERβ gene expression but did not decrease ERα expression nor did it switch hydroxy-tamoxifen to an agonist activity. Altogether, these data suggest that the class II HDAC sub-family may exert specific roles in breast cancer progression and estrogen-dependence. PMID:19074835

Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

ClinicalTrials.gov

2018-02-08

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

Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system.

PubMed

Fisher, S; Gao, H; Yasui, Y; Dabbs, K; Winget, M

2015-06-01

Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada. Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received. A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival. Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer | Division of Cancer Prevention

Cancer.gov

This randomized phase IIb trial studies how well alternative dosing of exemestane before surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the exemestane

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

ClinicalTrials.gov

2017-07-28

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

Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women.

PubMed

2010-01-01

Recent findings indicate a greater risk of postmenopausal breast cancer with estrogen-progestagen therapy than estrogen monotherapy, and more so for current than past use. Few studies have examined individual genetic susceptibility to the effects of menopausal hormone therapy. We used two population-based case-control studies with 3,155 postmenopausal breast cancer patients and 5,496 controls to evaluate modification of breast cancer risk associated with duration of hormone use by genes involved in hormone metabolism and detoxification. Twenty-eight polymorphisms in eight genes of phase I (CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP3A7) and nine genes of phase II enzymes (COMT, GSTM1, GSTM3, GSTP1, GSTT1, SULT1A1, UGT1A1, UGT1A6, UGT2B7) were genotyped. The risk associated with duration of use of combined estrogen-progestagen therapy was significantly modified by genetic polymorphisms located in CYP1B1, GSTP1, and GSTT1. In homozygote carriers of the CYP1B1_142_G and the CYP1B1_355 _T variant alleles, adjusted odds ratios (OR) per year of use were 1.06 (95% confidence interval (CI) = 1.02-1.09) and 1.06 (95% CI = 1.03-1.09), respectively, compared with 1.02 (95% CI = 1.01-1.03) in non-carriers of either polymorphism (p(interaction) = 0.01). Carriers of the functional GSTT1 allele and the GSTP1_341_T allele were at significantly higher risks associated with hormone use compared with non-carriers (p(interaction) = 0.0001 and 0.02). CYP1A1_2452_C>A significantly reduced the risk associated with duration of use of estrogen monotherapy (p(interaction) = 0.01). The finding regarding GSTT1 was still statistically significant after corrections for multiple comparisons. Postmenopausal breast cancer risk associated with hormone therapy may be modified by genetically determined variations in phase I and II enzymes involved in steroid hormone metabolism.

Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

ClinicalTrials.gov

2017-06-07

Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

Dietary practices and nutritional status in survivors of breast cancer

PubMed

Kałędkiewicz, Emilia; Szostak-Węgierek, Dorota

2018-01-01

Wrong dietary practices and excessive body mass may not only influence the risk of primary breast cancer but also the risk of its recurrence. Evaluation of dietary practices and identification of nutritional factors which may influence the risk of tumor recurrence in women with prior breast cancer. The case-control study involved 108 women aged 50 years and older with history of breast cancer who were divided into two categories: women after completed cancer treatment with no recurrence for minimum 5 years (group I, n=82) and women with diagnosed breast cancer recurrence (group II, n=26). A control group (n=74) constituted of subjects with no breast cancer diagnosis. In every subject anthropometric measurements were taken and dietary practices were evaluated by means of an original questionnaire. Average BMI and hip circumference values were higher in the group II than in the group I. In both study groups the percentage of high WHR values was significantly higher than in the control group. Women with history of cancer consumed significantly fewer vegetable and fruit and more refined cereals, dairy products, meat and cold cuts than women in the control group. Group I responders more often declared implementation and maintenance of changes in their diet after diagnosis of cancer than women from group II. Subjects with cancer history consumed more alcohol and more often used supplements than females in the control group. Avoiding overweight and obesity along with following the principles of a healthy diet seems to reduce the risk of both breast cancer incidence and its recurrence.

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

ClinicalTrials.gov

2017-04-12

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

MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection

PubMed Central

Rozanov, Dmitri V.; Rozanov, Nikita D.; Chiotti, Kami; Reddy, Ashok; Wilmarth, Phillip A.; David, Larry L.; Cha, Seung W.; Woo, Sunghee; Pevzner, Pavel; Bafna, Vineet; Burrows, Gregory G.; Rantala, Juha K.; Levin, Trevor; Anur, Pavana; Johnson-Camacho, Katie; Tabatabaei, Shaadi; Munson, Daniel J.; Bruno, Tullia C.; Slansky, Jill E.; Kappler, John W.; Hirano, Naoto; Boegel, Sebastian; Fox, Bernard A.; Egelston, Colt; Simons, Diana L.; Jimenez, Grecia; Lee, Peter P.; Gray, Joe W.; Spellman, Paul T.

2018-01-01

Breast cancer therapy based on amplifying a patient’s antitumor immune response depends on the availability of appropriate MHC class I-restricted, breast cancer-specific epitopes. To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cell lines. We determined the sequence of 3,196 MHC class I-bound peptides representing 1,921 proteins from a panel of 20 breast cancer cell lines including basal, luminal, and claudin-low subtypes. The data has been deposited to the ProteomeXchange with identifier PXD006406. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2,740. Of the unique peptides eluted, more than 1,750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, only 3 of these immunogenic peptides have been identified in breast cancer cells in earlier studies. MHC class I binding probability of eluted peptides was used to plot the distribution of MHC class I allele-specific peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines. PMID:29331515

Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort.

PubMed

Wang, Ying; Gapstur, Susan M; Gaudet, Mia M; Furtado, Jeremy D; Campos, Hannia; McCullough, Marjorie L

2015-09-01

Several circulating carotenoids have been inversely associated with postmenopausal breast cancer risk in large cohort studies and a pooled analysis. Whether associations differ by tumor or participant characteristics remains unclear. We investigated the associations of plasma carotenoids with postmenopausal breast cancer risk overall and by estrogen receptor (ER) status, tumor stage, smoking status, and body mass index, in a case-control study nested in the Cancer Prevention Study II Nutrition Cohort. A total of 496 invasive breast cancer cases diagnosed between blood draw in 1998-2001 and June 30, 2007 and matched 1:1 with controls on race, birth date, and blood draw date were included. Multivariable-adjusted conditional and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Plasma α-carotene above the lowest quartile was associated with significant 40-43% lower risk of invasive breast cancer risk (fourth vs. first quartile OR 0.60, 95% CI 0.41-0.87, P-trend = 0.037) after adjustment for multiple covariates. This inverse association was strengthened after further adjustment for other plasma carotenoids and total fruit and vegetable intake (fourth vs. first quartile OR 0.50, 95% CI 0.29-0.85, P-trend = 0.041). Other plasma carotenoids or total carotenoids were not associated with breast cancer risk. The inverse association of α-carotene with breast cancer remained for ER+, but not for ER- tumors, although test for heterogeneity was not statistically significant (P-heterogeneity = 0.49). These results suggest that higher plasma α-carotene is associated with lower risk of invasive breast cancer.

[Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer].

PubMed

Liu, Xin; Liu, Qi-feng; Xu, Ye; Ouyang, Tao; Li, Jin-feng; Wang, Tian-feng; Fan, Zhao-qing; Fan, Tie; Lin, Ben-yao; Xie, Yun-tao

2011-07-12

To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer. A total of 1538 female patients with operable primary breast cancer (stage I-III) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (≤ 60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group (≤ 40 yrs, n = 208) and control group (41 - 60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups. The patients with young breast cancer were more likely to have positive lymph nodes (P = 0.016), a negative expression of ER (estrogen receptor) (P = 0.016) and a positive expression of HER2 (P = 0.001). The 5-year disease-free survival (DFS) rates of young breast cancer group and control group were 73.3% and 84.1% (P < 0.001) and the 5-year overall survival (OS) rates 83.5% and 89.1% (P = 0.004) respectively. Moreover, the patients with young breast cancer had a worse DFS than control group in patients with stage I-II disease but not in those with stage III disease. And ≤ 40 years was an independent unfavorable prognostic factor of DFS (HR = 1.78, 95%CI: 1.19 - 2.66, P = 0.005) and OS (HR = 1.71, 95%CI: 1.01 - 2.90, P = 0.046) in the patients with stage I-II disease. Chinese women with young breast cancer have a worse prognosis, particularly in those with stage I-II disease.

Can differences in breast cancer utilities explain disparities in breast cancer care?

PubMed

Schleinitz, Mark D; DePalo, Dina; Blume, Jeffrey; Stein, Michael

2006-12-01

Black, older, and less affluent women are less likely to receive adjuvant breast cancer therapy than their counterparts. Whereas preference contributes to disparities in other health care scenarios, it is unclear if preference explains differential rates of breast cancer care. To ascertain utilities from women of diverse backgrounds for the different stages of, and treatments for, breast cancer and to determine whether a treatment decision modeled from utilities is associated with socio-demographic characteristics. A stratified sample (by age and race) of 156 English-speaking women over 25 years old not currently undergoing breast cancer treatment. We assessed utilities using standard gamble for 5 breast cancer stages, and time-tradeoff for 3 therapeutic modalities. We incorporated each subject's utilities into a Markov model to determine whether her quality-adjusted life expectancy would be maximized with chemotherapy for a hypothetical, current diagnosis of stage II breast cancer. We used logistic regression to determine whether socio-demographic variables were associated with this optimal strategy. Median utilities for the 8 health states were: stage I disease, 0.91 (interquartile range 0.50 to 1.00); stage II, 0.75 (0.26 to 0.99); stage III, 0.51 (0.25 to 0.94); stage IV (estrogen receptor positive), 0.36 (0 to 0.75); stage IV (estrogen receptor negative), 0.40 (0 to 0.79); chemotherapy 0.50 (0 to 0.92); hormonal therapy 0.58 (0 to 1); and radiation therapy 0.83 (0.10 to 1). Utilities for early stage disease and treatment modalities, but not metastatic disease, varied with socio-demographic characteristics. One hundred and twenty-two of 156 subjects had utilities that maximized quality-adjusted life expectancy given stage II breast cancer with chemotherapy. Age over 50, black race, and low household income were associated with at least 5-fold lower odds of maximizing quality-adjusted life expectancy with chemotherapy, whereas women who were married or had a

Psychosocial adjustment among women with breast cancer stages I and II: six-year follow-up of consecutive patients.

PubMed

Omne-Pontén, M; Holmberg, L; Sjödén, P O

1994-09-01

To evaluate, in a long-term follow-up study of consecutive patients (N = 99), the impact of surgery--breast-conserving treatment (BCT) versus mastectomy (MT)--on psychosocial adjustment among women with breast cancer, pTNM stage I/II. Semistructured interviews were conducted at a median of 6 years (range, 5.8 to 8.1) after primary surgery. Sixty-six women were available for the long-term follow-up study. Twenty-six women had been treated with BCT and 40 with MT. No statistically significant differences were found between the two groups concerning psychosocial adjustment, as measured by the Social adjustment Scale (SAS). In general, the levels of maladjustment were lower than at 13 months postoperatively, but 10% still showed maladjustment. Sixty percent of the women were unwilling to show themselves naked, and 22% felt that they had become less attractive because of the surgical treatment. In an explorative part of the interview, 68% of the women complained about how they had been informed of the diagnosis. A tendency toward a significant difference was found in the relation between previous maladjustment and a negative experience at the time of diagnosis (P = .07). Few data are available on long-term follow-up results with regard to psychosocial adjustment among women after breast cancer surgery. This study provides the important information that there are no differences in patient psychosocial adjustment that can be ascribed to the type of surgery at 6-year follow-up evaluation.

Breast cancer treatment costs in younger, privately insured women.

PubMed

Allaire, Benjamin T; Ekwueme, Donatus U; Poehler, Diana; Thomas, Cheryll C; Guy, Gery P; Subramanian, Sujha; Trogdon, Justin G

2017-07-01

Younger women (under age 45 years) diagnosed with breast cancer often face more aggressive tumors, higher treatment intensity, lower survival rates, and greater financial hardship. The purpose of this study was to estimate breast cancer costs by stage at diagnosis during the first 18 months of treatment for privately insured younger women. We analyzed North Carolina cancer registry data linked to claims data from private insurers from 2003 to 2010. Breast cancer patients were split into two cohorts: a younger and older group aged 21-44 and 45-64 years, respectively. We conducted a cohort study and matched women with and without breast cancer using age, ZIP, and Charlson Comorbidity Index. We calculated mean excess costs between breast cancer and non-breast cancer patients at 6, 12, and 18 months. For younger women, AJCC 6th edition stage II cancer was the most common at diagnosis (40%), followed by stage I (34%). On the other hand, older women had more stage I (46%) cancer followed by stage II (34%). The excess costs for younger and older women at 12 months were $97,486 (95% confidence interval [CI] $93,631-101,341) and $75,737 (95% CI $73,962-77,512), respectively. Younger breast cancer patients had both a higher prevalence of later-stage disease and higher within-stage costs. The study reports high costs of treatment for both younger and older women than a non-cancer comparison group; however, the estimated excess cost was significantly higher for younger women. The financial implications of breast cancer treatment costs for younger women need to be explored in future studies.

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

PubMed

Jedy-Agba, Elima; McCormack, Valerie; Olaomi, Oluwole; Badejo, Wunmi; Yilkudi, Monday; Yawe, Terna; Ezeome, Emmanuel; Salu, Iliya; Miner, Elijah; Anosike, Ikechukwu; Adebamowo, Sally N; Achusi, Benjamin; Dos-Santos-Silva, Isabel; Adebamowo, Clement

2017-07-01

Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

The After Breast Cancer Pooling Project: rationale, methodology, and breast cancer survivor characteristics.

PubMed

Nechuta, Sarah J; Caan, Bette J; Chen, Wendy Y; Flatt, Shirley W; Lu, Wei; Patterson, Ruth E; Poole, Elizabeth M; Kwan, Marilyn L; Chen, Zhi; Weltzien, Erin; Pierce, John P; Shu, Xiao Ou

2011-09-01

The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.7%). About 60% of breast tumors were estrogen receptor (ER)+/progesterone receptor (PR)+; 21% were ER-/PR-. Among 8,118 participants with information on HER-2 tumor status, 74.8% were HER-2- and 18.5% were HER-2+. At 1-2 years post-diagnosis (on average), 17.9% of participants were obese (BMI ≥ 30 kg/m2), 32.6% were overweight (BMI 25-29 kg/m2), and 59.9% met the 2008 Physical Activity Guidelines for Americans (≥ 2.5 h per week of moderate activity). During follow-up (mean = 8.4 years), 3,736 deaths (2,614 from breast cancer) and 3,564 recurrences have been documented. After accounting for differences in year of diagnosis and timing of post-diagnosis enrollment, five-year overall survival estimates were similar across cohorts. This pooling project of 18,000 breast cancer survivors enables the evaluation of associations of post-diagnosis lifestyle factors, QOL, and breast cancer outcomes with an adequate sample size for investigation of heterogeneity by hormone receptor status and other clinical predictors. The project sets the stage for international collaborations for the investigation of modifiable predictors for breast cancer outcomes.

Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells.

PubMed

Cambados, Nadia; Walther, Thomas; Nahmod, Karen; Tocci, Johanna M; Rubinstein, Natalia; Böhme, Ilka; Simian, Marina; Sampayo, Rocío; Del Valle Suberbordes, Melisa; Kordon, Edith C; Schere-Levy, Carolina

2017-10-24

Angiotensin (Ang) II, the main effector peptide of the renin-angiotensin system, has been implicated in multiple aspects of cancer progression such as proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a biologically active heptapeptide, generated predominantly from AngII by the enzymatic activity of angiotensin converting enzyme 2. Previous studies have shown that Ang-(1-7) counterbalances AngII actions in different pathophysiological settings. In this study, we have analysed the impact of Ang-(1-7) on AngII-induced pro-tumorigenic features on normal murine mammary epithelial cells NMuMG and breast cancer cells MDA-MB-231. AngII stimulated the activation of the survival factor AKT in NMuMG cells mainly through the AT1 receptor. This PI3K/AKT pathway activation also promoted epithelial-mesenchymal transition (EMT). Concomitant treatment of NMuMG cells with AngII and Ang-(1-7) completely abolished EMT features induced by AngII. Furthermore, Ang-(1-7) abrogated AngII induced migration and invasion of the MDA-MB-231 cells as well as pro-angiogenic events such as the stimulation of MMP-9 activity and VEGF expression. Together, these results demonstrate for the first time that Ang-(1-7) counteracts tumor aggressive signals stimulated by AngII in breast cancer cells emerging the peptide as a potential therapy to prevent breast cancer progression.

Environmental radon exposure and breast cancer risk in the Nurses' Health Study II.

PubMed

VoPham, Trang; DuPré, Natalie; Tamimi, Rulla M; James, Peter; Bertrand, Kimberly A; Vieira, Veronica; Laden, Francine; Hart, Jaime E

2017-09-07

Radon and its decay products, a source of ionizing radiation, are primarily inhaled and can deliver a radiation dose to breast tissue, where they may continue to decay and emit DNA damage-inducing particles. Few studies have examined the relationship between radon and breast cancer. The Nurses' Health Study II (NHSII) includes U.S. female registered nurses who completed biennial questionnaires since 1989. Self-reported breast cancer was confirmed from medical records. County-level radon exposures were linked with geocoded residential addresses updated throughout follow-up. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). From 1989 to 2013, 3966 invasive breast cancer cases occurred among 112,639 participants. Increasing radon exposure was not associated with breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.06, 95% CI: 0.94, 1.21, p for trend = 0.30). However, women in the highest quintile of exposure (≥74.9 Bq/m 3 ) had a suggested elevated risk of ER-/PR- breast cancer compared to women in the lowest quintile (<27.0 Bq/m 3 ) (adjusted HR = 1.38, 95% CI: 0.97, 1.96, p for trend = 0.05). No association was observed for ER+/PR+ breast cancer. Although we did not find an association between radon exposure and risk of overall or ER+/PR+ breast cancer, we observed a suggestive association with risk of ER-/PR- breast cancer.

Educating Normal Breast Mucosa to Prevent Breast Cancer

DTIC Science & Technology

2015-05-01

is being determined. Finding # 1 : Pregnancy is associated with a relative increase in the levels of αβ TCR T cells. Data collection for subtype 1b...peptide OT-I/OT-II vaccine admixed with CFA /IFA. Three vaccinations were given over the course of 1 week. As shown in Figure 7, fairly strong T cell... 1 Award Number: W81XWH-12- 1 -0059 TITLE: Educating normal breast mucosa to prevent breast cancer PRINCIPAL INVESTIGATOR: Keith L Knutson

Breast Cancer Lymphatic Dissemination - Influence of Estrogen and Progesterone

DTIC Science & Technology

2008-03-01

illustrative cases. Lancet 1896;2:104–7. 32. Koda M, Sulkowski S, Kanczuga- Koda L, Surmacz E, Sulkowska M. Expression of ERa, ERh and Ki-67 in primary tumors...10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 1992;28A: 801–5. 36. Koda M, Lenczewski A

Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone

DTIC Science & Technology

2008-10-01

illustrative cases. Lancet 1896;2:104–7. 32. Koda M, Sulkowski S, Kanczuga- Koda L, Surmacz E, Sulkowska M. Expression of ERa, ERh and Ki-67 in primary...trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 1992;28A: 801–5. 36. Koda M, Lenczewski A

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

PubMed

Cuzick, Jack; Sestak, Ivana; Cawthorn, Simon; Hamed, Hisham; Holli, Kaija; Howell, Anthony; Forbes, John F

2015-01-01

Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group

Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-06-08

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

SNP rs2071095 in LincRNA H19 is associated with breast cancer risk.

PubMed

Cui, Ping; Zhao, Yanrui; Chu, Xinlei; He, Na; Zheng, Hong; Han, Jiali; Song, Fengju; Chen, Kexin

2018-05-08

An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r 2  < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes. We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.

Dietary Energy Density and Postmenopausal Breast Cancer Incidence in the Cancer Prevention Study II Nutrition Cohort.

PubMed

Hartman, Terryl J; Gapstur, Susan M; Gaudet, Mia M; Shah, Roma; Flanders, W Dana; Wang, Ying; McCullough, Marjorie L

2016-10-01

Dietary energy density (ED) is a measure of diet quality that estimates the amount of energy per unit of food (kilocalories per gram) consumed. Low-ED diets are generally high in fiber and fruits and vegetables and low in fat. Dietary ED has been positively associated with body mass index (BMI) and other risk factors for postmenopausal breast cancer. We evaluated the associations of total dietary ED and energy-dense (high-ED) foods with postmenopausal breast cancer incidence. Analyses included 56,795 postmenopausal women from the Cancer Prevention Study II Nutrition Cohort with no previous history of breast or other cancers and who provided information on diet, lifestyle, and medical history in 1999. Multivariable-adjusted breast cancer incidence rate ratios (RRs and 95% CIs) were estimated for quintiles of total dietary ED and for the consumption of high-ED foods in Cox proportional hazards regression models. During a median follow-up of 11.7 y, 2509 invasive breast cancer cases were identified, including 1857 estrogen receptor-positive and 277 estrogen receptor-negative tumors. Median dietary ED was 1.5 kcal/g (IQR: 1.3-1.7 kcal/g). After adjusting for age, race, education, reproductive characteristics, and family history, high compared with low dietary ED was associated with a statistically significantly higher risk of breast cancer (RR for fifth quintile compared with first quintile: 1.20; 95% CI: 1.05, 1.36; P-trend = 0.03). The association between the amount of high-ED foods consumed and breast cancer risk was not statistically significant. We observed no differences by estrogen receptor status or effect modification by BMI, age, or physical activity. These results suggest a modest positive association between total dietary ED and risk of postmenopausal breast cancer. © 2016 American Society for Nutrition.

Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

PubMed

Han, K; Yap, M L; Yong, J H E; Mittmann, N; Hoch, J S; Fyles, A W; Warde, P; Gutierrez, E; Lymberiou, T; Foxcroft, S; Liu, F F

2016-09-01

The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Theranostics Targeting Metastatic Breast Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0389 TITLE: Theranostics Targeting Metastatic Breast Cancer PRINCIPAL INVESTIGATOR: Kevin Burgess CONTRACTING...ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 4. TITLE AND SUBTITLE Theranostics Targeting Metastatic Breast Cancer 5a...safe and effective interventions; (ii) elimination of mortality associated with metastatic breast cancer ; and, (iii) distinguishing aggressive breast

Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

PubMed

Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

Real-Time Moment-to-Moment Emotional Responses to Narrative and Informational Breast Cancer Videos in African American Women

ERIC Educational Resources Information Center

Bollinger, Sarah; Kreuter, Matthew W.

2012-01-01

In a randomized experiment using moment-to-moment audience analysis methods, we compared women's emotional responses with a narrative versus informational breast cancer video. Both videos communicated three key messages about breast cancer: (i) understand your breast cancer risk, (ii) talk openly about breast cancer and (iii) get regular…

CD1d-Expressing Breast Cancer Cells Modulate NKT Cell-Mediated Antitumor Immunity in a Murine Model of Breast Cancer Metastasis

PubMed Central

Hix, Laura M.; Shi, Yihui H.; Brutkiewicz, Randy R.; Stein, Paul L.; Wang, Chyung-Ru; Zhang, Ming

2011-01-01

Background Tumor tolerance and immune suppression remain formidable obstacles to the efficacy of immunotherapies that harness the immune system to eradicate breast cancer. A novel syngeneic mouse model of breast cancer metastasis was developed in our lab to investigate mechanisms of immune regulation of breast cancer. Comparative analysis of low-metastatic vs. highly metastatic tumor cells isolated from these mice revealed several important genetic alterations related to immune control of cancer, including a significant downregulation of cd1d1 in the highly metastatic tumor cells. The cd1d1 gene in mice encodes the MHC class I-like molecule CD1d, which presents glycolipid antigens to a specialized subset of T cells known as natural killer T (NKT) cells. We hypothesize that breast cancer cells, through downregulation of CD1d and subsequent evasion of NKT-mediated antitumor immunity, gain increased potential for metastatic tumor progression. Methodology/Principal Findings In this study, we demonstrate in a mouse model of breast cancer metastasis that tumor downregulation of CD1d inhibits iNKT-mediated antitumor immunity and promotes metastatic breast cancer progression in a CD1d-dependent manner in vitro and in vivo. Using NKT-deficient transgenic mouse models, we demonstrate important differences between type I and type II NKT cells in their ability to regulate antitumor immunity of CD1d-expressing breast tumors. Conclusions/Significance The results of this study emphasize the importance of determining the CD1d expression status of the tumor when tailoring NKT-based immunotherapies for the prevention and treatment of metastatic breast cancer. PMID:21695190

Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

PubMed Central

Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

2015-01-01

Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer.

PubMed Central

Baker, R R; Holmes, E R; Alderson, P O; Khouri, N F; Wagner, H N

1977-01-01

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients. Images Figs. 1a and b. Figs. 2a and b. Figs. 3a-d. PMID:889378

Prevention and treatment of breast cancer by suppressing aromatase activity and expression.

PubMed

Chen, Shiuan; Zhou, Dujin; Okubo, Tomoharu; Kao, Yeh-Chih; Eng, Elizabeth T; Grube, Baiba; Kwon, Annette; Yang, Chun; Yu, Bin

2002-06-01

Estrogen promotes the proliferation of breast cancer cells. Aromatase is the enzyme that converts androgen to estrogen. In tumors, expression of aromatase is upregulated compared to that of surrounding noncancerous tissue. Tumor aromatase is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner. A treatment strategy for breast cancer is to abolish in situ estrogen formation with aromatase inhibitors. In addition, aromatase suppression in postmenapausal women is being evaluated as a potential chemopreventive modality against breast cancer. One area of aromatase research in this laboratory is the identification of foods and dietary compounds that can suppress aromatase activity. In vitro and in vivo studies have found that grapes and mushrooms contain chemicals that can inhibit aromatase. Therefore, a diet that includes grapes and mushrooms would be considered preventative against breast cancer. Another area of our aromatase research is the elucidation of the regulatory mechanism of aromatase expression in breast cancer tissue. Increased aromatase expression in breast tumors is attributed to changes in the transcriptional control of aromatase expression. Whereas promoter I.4 is the main promoter that controls aromatase expression in noncancerous breast tissue, promoters II and I.3 are the dominant promoters that drive aromatase expression in breast cancer tissue. Our recent gene regulation studies revealed that in cancerous versus normal tissue, several positive regulatory proteins (e.g., nuclear receptors and CREB1) are present at higher levels and several negative regulatory proteins (e.g., snail and slug proteins) are present at lower levels. This may explain why the activity of promoters II and I.3 is upregulated in cancerous tissue. In addition, our in vitro transcription/translation analysis using plasmids containing T7 promoter and the human snail gene as a reporter capped with different untranslated exon Is revealed that exon

Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast | Division of Cancer Prevention

Cancer.gov

This randomized phase II trial studies how well afimoxifene works in reducing the risk of breast cancer in women with mammographically dense breast. Estrogen can cause the growth of breast cancer cells. Hormone therapy using afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells. |

Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer.

PubMed

Rodler, Eve T; Kurland, Brenda F; Griffin, Melissa; Gralow, Julie R; Porter, Peggy; Yeh, Rosa F; Gadi, Vijayakrishna K; Guenthoer, Jamie; Beumer, Jan H; Korde, Larissa; Strychor, Sandra; Kiesel, Brian F; Linden, Hannah M; Thompson, John A; Swisher, Elizabeth; Chai, Xiaoyu; Shepherd, Stacie; Giranda, Vincent; Specht, Jennifer M

2016-06-15

Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) and BRCA mutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine. A 3+3 dose-escalation design evaluated veliparib administered twice daily for 14 days with cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1, 8) every 21 days, for 6 to 10 cycles, followed by veliparib monotherapy. Pharmacokinetics, measurement of poly(ADP-ribose) in peripheral blood mononuclear cells, and preliminary efficacy were assessed. IHC and gene-expression profiling were evaluated as potential predictors of response. Forty-five patients enrolled in nine dose cohorts plus five in an expansion cohort at the highest dose level and recommended phase II dose, 300 mg twice daily. The MTD of veliparib was not reached. Neutropenia (36%), anemia (30%), and thrombocytopenia (12%) were the most common grade 3/4 adverse events. Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%). Germline BRCA mutation presence versus absence was associated with 6-month progression-free survival [PFS; 10 of 14 (71%) vs. 8 of 27 (30%), mid-P = 0.01]. Median PFS for all 50 patients was 5.5 months (95% confidence interval, 4.1-6.7). Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates. A phase II randomized trial is planned to assess veliparib's contribution to cisplatin chemotherapy in metastatic TNBC and BRCA mutation-associated breast cancer. Clin Cancer Res; 22(12); 2855-64. ©2016 AACR. ©2016 American Association for Cancer Research.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease.

PubMed

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A

2015-11-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4-5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease

PubMed Central

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A.

2015-01-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4–5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. PMID:26255741

A phase II study of mitoxantrone in advanced breast cancer.

PubMed

Pronzato, P; Ardizzoni, A; Conte, P F; Gulisano, M; Lionetto, R; Repetto, L; Scornavacche, V; Sertoli, M R; Rosso, R

1986-06-01

A phase II study with mitoxantrone has been carried out in 30 metastatic breast cancer patients. Of 26 evaluable patients 7 (26.9%) experienced a partial response; 7 (26.9%) patients had stable disease and 12 (46.1%) had progression. Major toxicity observed was: nausea and vomiting in 52% of patients, moderate hair loss in 53% of patients and leukopenia in 53%.

[Proteome analysis for identification of tumor-associated biomarkers in breast cancer].

PubMed

Wang, Xi; Liang, Wei-Jiang; Zhu, Zhen-Yu; Yang, Ming-Tian; Zeng, Yi-Xin

2004-11-01

Pre-symptomatic screening of early-stage breast cancer may greatly reduce tumor-related mortality. Some tumor markers, such as CA15-3 and CA27-29, are recommended only for monitoring therapy of advanced or relapsed breast cancer. This study was to find new biomarkers that could be used individually or in combination with an existing modality for cost-effective screening of breast cancer by proteome analysis. Protein expression differences among 128 serum samples of 64 breast cancer patients (19 of stage I, 24 of stage II, and 21 of stage III), 52 patients with benign breast diseases, and 12 healthy women were analyzed with IMAC3 and WCX2 Ciphergen ProteinChip Arrays. On WCX2 chip, a panel of 5 proteins (9 116, 8 905, 8 749, 9 470, and 9 692 Da) was selected based on their collective contribution to the optimal separation between breast cancer patients and both non-cancer patients and healthy women, and expression of another 2 proteins (9 405 and 6 424 Da) was different between patients with breast cancer of stage I and stage III. On IMAC3 chip, a panel of 9 proteins (5 236, 7 823, 7 464, 5 213, 5 334, 5 064, 5 374, 7 756, and 7 623 Da) was selected based on their collective contribution to the optimal separation between breast cancer patients and both non-cancer patients and healthy women, and expression of another 3 proteins (7 922, 4 641, and 5 910 Da) was different between patients with breast cancer of stage I and stage III. Protein expression in breast cancer patients is different from that in both non-cancer patients and healthy women, and those proteins with different expression may be used as new biomarkers in breast cancer.

Predictive value of PET-CT for pathological response in stages II and III breast cancer patients following neoadjuvant chemotherapy with docetaxel.

PubMed

García García-Esquinas, Marta A; Arrazola García, Juan; García-Sáenz, José A; Furió-Bacete, V; Fuentes Ferrer, Manuel E; Ortega Candil, Aída; Cabrera Martín, María N; Carreras Delgado, José L

2014-01-01

To prospectively study the value of PET-CT with fluorine-18 fluorodeoxyglucose (FDG) to predict neoadjuvant chemotherapy (NAC) response of locoregional disease of stages II and III breast cancer patients. A written informed consent and approval were obtained from the Ethics Committee. PET-CT accuracy in the prediction of pathologic complete response (pCR) after NAC was studied in primary tumors and lymph node metastasis in 43 women (mean age: 50 years: range: 27-71 years) with histologically proven breast cancer between December 2009 and January 2011. PET-CT was performed at baseline and after NAC. SUV(max) percentage changes (ΔSUV(max)) were compared with pathology findings at surgery. Receiver-operator characteristic (ROC) analysis was used to discriminate between locoregional pCR and non-pCR. In patients not achieving pCR, it was investigated if ΔSUV(max) could accurately identify the residual cancer burden (RCB) classes: RCB-I (minimal residual disease (MRD)), RCB-II (moderate RD), and RCB-III (extensive RD). pCR was obtained in 11 patients (25.6%). Residual disease was found in 32 patients (74.4%): 16 (37.2%) RCB-I, 15 (35.6%) RCB-II and 2 (4.7%) RCB-III. Sensitivity, specificity, and accuracy to predict pCR were 90.9%, 90.6%, and 90.7%, respectively. Specificity was 94.1% in the identification of a subset of patients who had either pCR or MRD. Accuracy of ΔSUV(max) in the locoregional disease of stages II and III breast cancer patients after NAC is high for the identification of pCR cases. Its specificity is potentially sufficient to identify a subgroup of patients who could be managed with conservative surgery. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

PubMed

Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

2016-03-01

In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

m-RNA mammaglobin expression in metastatic breast cancer patient at Medan city, Indonesia

NASA Astrophysics Data System (ADS)

Rimbun, S.; Siregar, Y.

2018-03-01

Breast cancer is the most common causes of women’s death in the world. Metastatic spread presents a major clinical problem in about 30% of the patients. The study aims to investigate the clinical reliability of mammaglobin mRNA as a marker of circulating cancer cells in breast cancer patients. The positivity of blood was analyzed in relation to clinical and pathological characteristics. This study was on 29 breast cancer patients (13 metastatic, 16 non- metastatic patients), where28 were invasive intraductal carcinoma type and 1 was invasive lobular carcinoma type. Breast cancer patients were according to the histologic grade into grade I (7 patients),grade II (6 patients) and grade III (15 patients). All individuals included in this study were subjected to detection of mammaglobin m-RNA of circulating tumor cells in peripheral blood using RT-PCR technique. Positivity for mammaglobin in blood samples was in 38% of patients with metastatic but not in the non-metastatic patients. The presence of mammaglobin correlated with metastatic tumor (P = 0.011). Mammaglobin overexpression in breast tissue was significantly positive in low-grade tumors (I and II).

The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis.

PubMed

Starrett, Gabriel J; Luengas, Elizabeth M; McCann, Jennifer L; Ebrahimi, Diako; Temiz, Nuri A; Love, Robin P; Feng, Yuqing; Adolph, Madison B; Chelico, Linda; Law, Emily K; Carpenter, Michael A; Harris, Reuben S

2016-09-21

Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a likely solution to this paradox. A3B-null tumours with this mutational bias have at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, A3H-I has robust activity in biochemical and cellular assays, similar to A3H-II after compensation for lower protein expression levels. Gly105 in A3H-I (versus Arg105 in A3H-II) results in lower protein expression levels and increased nuclear localization, providing a mechanism for accessing genomic DNA. A3H-I also associates with clonal TCA/T-biased mutations in lung adenocarcinoma suggesting this enzyme makes broader contributions to cancer mutagenesis. These studies combine to suggest that A3B and A3H-I, together, explain the bulk of 'APOBEC signature' mutations in cancer.

Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2017-11-15

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

Antibody-directed neutralization of annexin II (ANX II) inhibits neoangiogenesis and human breast tumor growth in a xenograft model.

PubMed

Sharma, Meena; Blackman, Marc R; Sharma, Mahesh C

2012-02-01

Activation of the fibrinolytic pathway has long been associated with human breast cancer. Plasmin is the major end product of the fibrinolytic pathway and is critical for normal physiological functions. The mechanism by which plasmin is generated in breast cancer is not yet fully described. We previously identified annexin II (ANX II), a fibrinolytic receptor, in human breast tumor tissue samples and observed a strong positive correlation with advanced stage cancer (Sharma et al., 2006a). We further demonstrated that tissue plasminogen activator (tPA) binds to ANX II in invasive breast cancer MDA-MB231cells, which leads to plasmin generation (Sharma et al., 2010). We hypothesize that ANX II-dependent plasmin generation in breast tumor is necessary to trigger the switch to neoangiogenesis, thereby stimulating a more aggressive cancer phenotype. Our immunohistochemical studies of human breast tumor tissues provide compelling evidence of a strong positive correlation between ANX II expression and neoangiogenesis, and suggest that ANX II is a potential target to slow or inhibit breast tumor growth by inhibiting neoangiogenesis. We now report that administration of anti-ANX II antibody potently inhibits the growth of human breast tumor in a xenograft model. Inhibition of tumor growth is at least partly due to attenuation of neoangiogenic activity within the tumor. In vitro studies demonstrate that anti-ANX II antibody inhibits angiogenesis on three dimensional matrigel cultures by eliciting endothelial cell (EC) death likely due to apoptosis. Taken together, these data suggest that selective disruption of the fibrinolytic activity of ANX II may provide a novel strategy for specific inhibition of neoangiogenesis in human breast cancer. Published by Elsevier Inc.

Obesity and Breast Cancer.

PubMed

Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

Breast cancer incidence in food- vs non-food-producing areas in Norway: possible beneficial effects of World War II

PubMed Central

Robsahm, T E; Tretli, S

2002-01-01

It has been suggested that World War II influenced breast cancer risk among Norwegian women by affecting adolescent growth. Diet changed substantially during the war, and the reduction in energy intake was assumed to be larger in non-food- producing than in food-producing municipalities. In the present study, we have looked at the influence of residential history in areas with and without food production on the incidence of breast cancer in a population-based cohort study consisting of 597 906 women aged between 30 and 64 years. The study included 7311 cases of breast cancer, diagnosed between 1964 and 1992. The risk estimates were calculated using a Poisson regression model. The results suggest that residential history may influence the risk of breast cancer, where the suggested advantageous effect of World War II seems to be larger in non-food-producing than in food-producing areas. Breast cancer incidence was observed to decline for the post-war cohorts, which is discussed in relation to diet. British Journal of Cancer (2002) 86, 362–366. DOI: 10.1038/sj/bjc/6600084 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11875700

Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

PubMed

Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

2013-09-01

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P < 0.05). Multivariate analysis revealed that KPS/RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P < 0.05). Our results suggested that triple-negative patients had a shorter interval between initial diagnosis and the development of BM than luminal A patients. Systemic treatments following WBRT improved the survival of RPA class II/III patients.

Human Papilloma Viruses and Breast Cancer – Assessment of Causality

PubMed Central

Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

Towards Prevention of Breast Cancer: What Are the Clinical Challenges?

PubMed

Borgquist, Signe; Hall, Per; Lipkus, Isaac; Garber, Judy E

2018-05-01

The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. There are several barriers to overcome before prevention becomes an established part of breast cancer management. The objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering the aspects relevant for a breast cancer prevention trial. Herein, the following five areas are discussed: (i) Adequate tools for identification of women at high risk of breast cancer suggestively entitled Prevent! Online. (ii) Consensus on the definition of high risk, which is regarded as mandatory for all risk communication and potential prophylactic interventions. (iii) Risk perception and communication regarding risk information. (iv) Potential ethical concerns relevant for future breast cancer prevention programs. (v) Risk-reducing programs involving multileveled prevention depending on identified risk. Taken together, devoted efforts from both policy makers and health care providers are warranted to improve risk assessment and risk counseling in women at risk for breast cancer to optimize the prevention of breast cancer. Cancer Prev Res; 11(5); 255-64. ©2018 AACR . ©2018 American Association for Cancer Research.

Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study.

PubMed

Kolarić, K; Potrebica, V; Vukas, D; Mechl, Z; Sopkova, B

1988-01-01

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination

MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

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

Hua, Wei; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an; Sa, Ke-Di

The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealedmore » that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.« less

Phase II Study of Bortezomib and Pegylated Liposomal Doxorubicin in the Treatment of Metastatic Breast Cancer

PubMed Central

Irvin, William J.; Orlowski, Robert Z.; Chiu, Wing-Keung; Carey, Lisa A.; Collichio, Frances A.; Bernard, Philip S.; Stijleman, Inge J.; Perou, Charles; Ivanova, Anastasia; Dees, E. Claire

2018-01-01

Background Based on preclinical studies and a phase I trial of the combination of bortezomib and pegylated liposomal doxorubicin (PLD), which both showed activity in breast cancer, we conducted a phase II study of this regimen in patients with metastatic breast cancer. Patients and Methods Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle, along with PLD 30 mg/m2 on day 4. The primary objective was to evaluate the response rate of this combination, while secondary objectives were to obtain further safety data about this combination, to evaluate the time to disease progression (TTP), and to evaluate response by the breast cancer subtype. Results One of 12 evaluable patients had a partial response (8%), while 3 (25%) had stable disease. At 26 months follow-up, the median overall survival was 4.3 months (95% CI, 1.2–26.2) and the median TTP was 1.3 months (95% CI, 0.8–14.0 months). The combination was well tolerated, with the most common events including low-grade nausea and vomiting, neutropenia, and neuropathy, and no cardiac toxicity was seen. Of the 7 tumors subtyped, no association was seen between intrinsic subtype or receptor status and response. Conclusion The combination of PLD and bortezomib was well tolerated but has minimal activity in heavily pretreated unselected metastatic breast cancer. PMID:21147690

[Trends in breast cancer treatment in the elderly at a breast cancer outpatient clinic: guidelines followed better].

PubMed

Hamaker, Marije E; Schreurs, W Hermien; van Slooten, Henk Jan; Uppelschoten, Jeroen M; Smorenburg, Carolien H

2009-01-01

To investigate the treatment of resectable breast cancer in elderly patients at Alkmaar Medical Centre, Alkmaar, the Netherlands, before and after the introduction of a multidisciplinary breast cancer consultation (MDC) with the breast cancer team in February 2006. Retrospective. The treatment of patients aged 70 and over with newly diagnosed stage I and II resectable breast cancer was monitored during the period 2002-2007. A total of 84% of the 232 studied patients were treated surgically. Adjuvant treatment with radiotherapy, hormone therapy and chemotherapy was given to 88, 91 and 5 patients, respectively. The percentage of patients who underwent first-line surgery decreased significantly, mainly because fewer patients aged 80 or over received surgery. The number of patients given radiotherapy in accordance with guidelines increased, while for hormonal therapy the number remained more or less the same. Recording of decisions that involved deviation from treatment guidelines improved in the study period. In 2002-2007, the breast cancer team became more aware of treatment guidelines and deviations from guidelines were better accounted for. In the elderly, the guidelines for adjuvant radiotherapy were followed better, but there was a remarkable decrease in primary surgical treatment of patients, particularly in patients aged 80 and over. Comorbidity and patients' preferences played an important role in this.

Loss in working years after a breast cancer diagnosis.

PubMed

Plym, Anna; Bower, Hannah; Fredriksson, Irma; Holmberg, Lars; Lambert, Paul C; Lambe, Mats

2018-03-06

Breast cancer can negatively influence working life, but it is unclear how many working years women with breast cancer can expect to lose. Women diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N=19 661), together with breast cancer-free comparison women (N=81 303). Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and without breast cancer. Women aged 50 years at diagnosis with stage I disease lost on average 0.5 years (95% CI, 0.2-0.7) of their remaining working time; the corresponding estimates were 0.9 years (0.5-1.2) in stage II, 2.5 years (1.9-3.1) in stage III and 8.1 years (6.5-9.7) in stage IV. Women with in situ breast cancer did not lose any working years. The strongest treatment determinant was axillary lymph node dissection. We found a loss in working years not only in late but also in early-stage breast cancer. Although it is reassuring that some groups had no or only a modest work loss, the economic consequences for society are considerable given the large number of women annually diagnosed with breast cancer.

Plasma Enterolactone and Breast Cancer Risk in the Nurses’ Health Study II

PubMed Central

Xie, Jing; Tworoger, Shelley S.; Franke, Adrian A.; Terry, Kathryn L.; Rice, Megan S.; Rosner, Bernard A.; Willett, Walter C.; Hankinson, Susan E.; Eliassen, A. Heather

2013-01-01

Background Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. Methods To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses’ Health Study II (NHSII) cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95% confidence intervals (CI). Results Compared to women with enterolactone concentrations ≤ 4nmol/L, the multivariate adjusted RRs for breast cancer were 1.18 (95% CI: 0.86–1.62), 0.91 (95% CI: 0.66–1.25), and 0.96 (95% CI: 0.70–1.33) for women with enterolactone levels in the 2nd to the 4th quartiles, respectively; Ptrend=0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51% lower breast cancer risk compared to those in the lowest category (95% CI: 0.27–0.91); Ptrend=0.02. No association was observed among women with high follicular estradiol levels (≥47 pg/mL), (comparable RR=1.39, 95% CI: 0.73–2.65; Pinteraction=0.02). Conclusions We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low follicular estradiol levels, suggesting that enterolactone may be important in a low estrogen environment. This should be confirmed in future

Breast cancer prevention and control programs in Malaysia.

PubMed

Dahlui, Maznah; Ramli, Sofea; Bulgiba, Awang M

2011-01-01

Breast cancer is the most common cancer in Malaysian females. The National Cancer Registry in 2003 and 2006 reported that the age standardized incidence of breast cancer was 46.2 and 39.3 per 100,000 populations, respectively. With the cumulative risk at 5.0; a woman in Malaysia had a 1 in 20 chance of developing breast cancer in her lifetime. The incidence of cancer in general, and for breast cancer specifically was highest in the Chinese, followed by Indians and Malays. Most of the patients with breast cancers presented at late stages (stage I: 15.45%, stage II: 46.9%, stage III: 22.2% and stage IV: 15.5%). The Healthy Lifestyles Campaign which started in the early nineties had created awareness on breast cancer and after a decade the effort was enhanced with the Breast Health Awareness program to promote breast self examination (BSE) to all women, to perform annual clinical breast examination (CBE) on women above 40 and mammogram on women above 50. The National Health Morbidity Survey in 2006 showed that the prevalence rate of 70.35% by any of three methods of breast screening; 57.1% by BSE, 51.8% by CBE and 7.6% by mammogram. The current screening policy for breast cancer focuses on CBE whereby all women at the age of 20 years and above must undergo breast examination by trained health care providers every 3 years for age between 20-39 years, and annually for age 40 and above. Several breast cancer preventive programs had been developed by various ministries in Malaysia; among which are the RM50 subsidy for mammogram by the Ministry of Women, Family and Community Development and the SIPPS program (a call-recall system for women to do PAP smear and CBE) by the Ministry of Health. Measures to increase uptake of breast cancer screening and factors as to why women with breast cancer present late should be studied to assist in more development of policy on the prevention of breast cancer in Malaysia.

Male breast cancer: 20-year survival data for post-mastectomy radiotherapy.

PubMed

Eggemann, Holm; Ignatov, Atanas; Stabenow, Roland; von Minckwitz, Gunter; Röhl, Friedrich Wilhelm; Hass, Peter; Costa, Serban-Dan

2013-08-01

The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer. We investigated 20-year OS rates of 664 patients diagnosed with primary stage I-III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy. Median follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41-0.88; p = 0.008). Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.

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

ClinicalTrials.gov

2017-05-25

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

Breast Retraction Assessment: an objective evaluation of cosmetic results of patients treated conservatively for breast cancer

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

Pezner, R.D.; Patterson, M.P.; Hill, L.R.

Breast Retraction Assessment (BRA) is an objective evaluation of the amount of cosmetic retraction of the treated breast in comparison to the untreated breast in patients who receive conservative treatment for breast cancer. A clear acrylic sheet supported vertically and marked as a grid at 1 cm intervals is employed to perform the measurements. Average BRA value in 29 control patients without breast cancer was 1.2 cm. Average BRA value in 27 patients treated conservatively for clinical Stage I or II unilateral breast cancer was 3.7 cm. BRA values in breast cancer patients ranged from 0.0 to 8.5 cm. Patientsmore » who received a local radiation boost to the primary tumor bed site had statistically significantly less retraction than those who did not receive a boost. Patients who had an extensive primary tumor resection had statistically significantly more retraction than those who underwent a more limited resection. In comparison to qualitative forms of cosmetic analysis, BRA is an objective test that can quantitatively evaluate factors which may be related to cosmetic retraction in patients treated conservatively for breast cancer.« less

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer.

PubMed

Elbaz, Mohamad; Ahirwar, Dinesh; Ravi, Janani; Nasser, Mohd W; Ganju, Ramesh K

2017-05-02

Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood. We observed that estrogen receptor-α negative (ERα-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERα+ breast cancer cells. In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERα- and ERα+ breast cancer patients. Therefore, we analyzed the role of CNR2 specific agonist (JWH-015) on EGF and/or IGF-I-induced tumorigenic events in ERα- and ERα+ breast cancers. Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERα+ and ERα- breast cancer cells. At the molecular level, JWH-015 inhibited EGFR and IGF-IR activation and their downstream targets STAT3, AKT, ERK, NF-kB and matrix metalloproteinases (MMPs). In vivo studies showed that JWH-015 significantly reduced breast cancer growth in ERα+ and ERα- breast cancer mouse models. Furthermore, we found that the tumors derived from JWH-015-treated mice showed reduced activation of EGFR and IGF-IR and their downstream targets. In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer.

PubMed

Steven, André; Seliger, Barbara

2018-03-01

While detailed analysis of aberrant cancer cell signaling pathways and changes in cancer cell DNA has dominated the field of breast cancer biology for years, there now exists increasing evidence that the tumor microenvironment (TME) including tumor-infiltrating immune cells support the growth and development of breast cancer and further facilitate invasion and metastasis formation as well as sensitivity to drug therapy. Furthermore, breast cancer cells have developed different strategies to escape surveillance from the adaptive and innate immune system. These include loss of expression of immunostimulatory molecules, gain of expression of immunoinhibitory molecules such as PD-L1 and HLA-G, and altered expression of components involved in apoptosis. Furthermore, the composition of the TME plays a key role in breast cancer development and treatment response. In this review we will focus on i) the different immune evasion mechanisms used by breast cancer cells, ii) the role of immune cell infiltration in this disease, and (iii) implication for breast cancer-based immunotherapies.

Analysis of framelets for breast cancer diagnosis.

PubMed

Thivya, K S; Sakthivel, P; Venkata Sai, P M

2016-01-01

Breast cancer is the second threatening tumor among the women. The effective way of reducing breast cancer is its early detection which helps to improve the diagnosing process. Digital mammography plays a significant role in mammogram screening at earlier stage of breast carcinoma. Even though, it is very difficult to find accurate abnormality in prevalent screening by radiologists. But the possibility of precise breast cancer screening is encouraged by predicting the accurate type of abnormality through Computer Aided Diagnosis (CAD) systems. The two most important indicators of breast malignancy are microcalcifications and masses. In this study, framelet transform, a multiresolutional analysis is investigated for the classification of the above mentioned two indicators. The statistical and co-occurrence features are extracted from the framelet decomposed mammograms with different resolution levels and support vector machine is employed for classification with k-fold cross validation. This system achieves 94.82% and 100% accuracy in normal/abnormal classification (stage I) and benign/malignant classification (stage II) of mass classification system and 98.57% and 100% for microcalcification system when using the MIAS database.

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.

Longitudinal analysis of domain-level breast cancer literacy among African-American women.

PubMed

Mabiso, Athur; Williams, Karen Patricia; Todem, David; Templin, Thomas N

2010-02-01

Functional breast cancer literacy was assessed among African-American women and measured at the domain level over time. We used the Kin Keeper(SM) Cancer Prevention Intervention to educate 161 African-American women on three domains of breast cancer literacy: (i) cancer awareness, (ii) knowledge of breast cancer screening modalities and (iii) cancer prevention and control. A breast cancer literacy assessment was administered pre- and post-educational intervention at two time points followed by another assessment 12 months after the second intervention. Generalized estimating equations were specified to predict the probability of correctly answering questions in each domain over time. Domain-level literacy differentials exist; at baseline, women had higher test scores in the breast cancer prevention and control domain than the cancer awareness domain (odds ratio = 1.67, 95% confidence interval 1.19-2.34). After Kin Keeper(SM) Cancer Prevention Intervention, African-American women consistently improved their breast cancer literacy in all domains over the five time stages (P < 0.001) though at different rates for each domain. Differences in domain-level breast cancer literacy highlight the importance of assessing literacy at the domain level. Interventions to improve African-American women's breast cancer literacy should focus on knowledge of breast cancer screening modalities and cancer awareness domains.

History of Gestational Diabetes Mellitus and Risk of Incident Invasive Breast Cancer among Parous Women in the Nurses' Health Study II Prospective Cohort.

PubMed

Powe, Camille E; Tobias, Deirdre K; Michels, Karin B; Chen, Wendy Y; Eliassen, A Heather; Manson, JoAnn E; Rosner, Bernard; Willett, Walter C; Hu, Frank B; Zhang, Cuilin; Rich-Edwards, Janet W; Rexrode, Kathryn M

2017-03-01

Background: Type II diabetes is associated with breast cancer in epidemiologic studies. Pregnancy also modifies breast cancer risk. We hypothesized that women with a history of gestational diabetes mellitus (GDM), which shares pathogenesis and risk factors with type II diabetes, would have greater invasive breast cancer risk than parous women without a history of GDM. Methods: We conducted a prospective analysis among parous women in the Nurses' Health Study II, with mean age 35 years in 1989. Multivariate Cox proportional hazards models were used to compare risks of incident invasive breast cancer in women with and without a history of GDM. Results: Among 86,972 women studied, 5,188 women reported a history of GDM and 2,377 developed invasive breast cancer (100 with history of GDM, 2,277 without GDM) over 22 years of prospective follow-up. History of GDM was inversely associated with incident invasive breast cancer [HR, 0.68; 95% confidence interval (CI), 0.55-0.84; P = 0.0004], compared with no history of GDM, after adjustment for body mass index, reproductive history, and other breast cancer risk factors. Findings were similar by menopausal status, although observed person-time was predominantly premenopausal (premenopausal: HR, 0.73; 95% CI, 0.56-0.96; P = 0.03; postmenopausal: HR, 0.63; 95% CI, 0.43-0.92; P = 0.02). Restricting to women undergoing mammography screening modestly attenuated the relationship (HR, 0.74; 95% CI, 0.57-0.96; P = 0.02). Conclusions: Among a large cohort of U.S. women, history of GDM was not associated with an elevated risk of subsequent invasive breast cancer. Impact: Our findings highlight the need to further investigate GDM's role in breast cancer development. Cancer Epidemiol Biomarkers Prev; 26(3); 321-7. ©2016 AACR . ©2016 American Association for Cancer Research.

Palbociclib: A new hope in the treatment of breast cancer.

PubMed

Palanisamy, R Priyadharsini

2016-01-01

Breast cancer being one of the common cancers has high morbidity and mortality. Despite the conventional treatment, the burden of the disease increases year after year. There is a need for newer drugs that target the different mechanisms in the pathogenesis. The interaction of cyclins with cyclin dependent kinases (CDKs) plays a major role in the abnormal cell cycle in cancer and it is considered to be an important target. Palbociclib is a CDK inhibitor currently approved for the treatment of breast cancer. The preclinical studies with breast cancer lines were sensitive to palbociclib and the clinical trials phase I, phase II (PALOMA 1), and phase III (PALOMA 2, 3, PENTELOPE, PEARL) showed that the drug was efficacious when combined other conventional drugs for breast cancer. Palbociclib was also been tested in various other germ cell tumors, melanoma, multiple myeloma, glioblastoma multiforme etc., The major adverse effect of the drug includes hematological toxicity mainly neutropenia, gastrointestinal adverse effects.

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

ClinicalTrials.gov

2016-10-11

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

Targeting Metabolic Plasticity in Breast Cancer Cells via Mitochondrial Complex I Modulation

PubMed Central

Xu, Qijin; Biener-Ramanujan, Eva; Yang, Wei; Ramanujan, V Krishnan

2016-01-01

Purpose Heterogeneity commonly observed in clinical tumors stems both from the genetic diversity as well as from the differential metabolic adaptation of multiple cancer types during their struggle to maintain uncontrolled proliferation and invasion in vivo. This study aims to identify a potential metabolic window of such adaptation in aggressive human breast cancer cell lines. Methods With a multidisciplinary approach using high resolution imaging, cell metabolism assays, proteomic profiling and animal models of human tumor xenografts and via clinically-relevant, pharmacological approach for modulating mitochondrial complex I function in human breast cancer cell lines, we report a novel route to target metabolic plasticity in human breast cancer cells. Results By a systematic modulation of mitochondrial function and by mitigating metabolic switch phenotype in aggressive human breast cancer cells, we demonstrate that the resulting metabolic adaptation signatures can predictably decrease tumorigenic potential in vivo. Proteomic profiling of the metabolic adaptation in these cells further revealed novel protein-pathway interactograms highlighting the importance of antioxidant machinery in the observed metabolic adaptation. Conclusions Improved metabolic adaptation potential in aggressive human breast cancer cells contribute to improving mitochondrial function and reducing metabolic switch phenotype –which may be vital for targeting primary tumor growth in vivo. PMID:25677747

Exposure to hazardous air pollutants and risk of incident breast cancer in the nurses' health study II.

PubMed

Hart, Jaime E; Bertrand, Kimberly A; DuPre, Natalie; James, Peter; Vieira, Verónica M; VoPham, Trang; Mittleman, Maggie R; Tamimi, Rulla M; Laden, Francine

2018-03-27

Findings from a recent prospective cohort study in California suggested increased risk of breast cancer associated with higher exposure to certain carcinogenic and estrogen-disrupting hazardous air pollutants (HAPs). However, to date, no nationwide studies have evaluated these possible associations. Our objective was to examine the impacts of mammary carcinogen and estrogen disrupting HAPs on risk of invasive breast cancer in a nationwide cohort. We assigned HAPs from the US Environmental Protection Agency's 2002 National Air Toxics Assessment to 109,239 members of the nationwide, prospective Nurses' Health Study II (NHSII). Risk of overall invasive, estrogen receptor (ER)-positive (ER+), and ER-negative (ER-) breast cancer with increasing quartiles of exposure were assessed in time-varying multivariable proportional hazards models, adjusted for traditional breast cancer risk factors. A total of 3321 invasive cases occurred (2160 ER+, 558 ER-) during follow-up 1989-2011. Overall, there was no consistent pattern of elevated risk of the HAPs with risk of breast cancer. Suggestive elevations were only seen with increasing 1,2-dibromo-3-chloropropane exposures (multivariable adjusted HR of overall breast cancer = 1.12, 95% CI: 0.98-1.29; ER+ breast cancer HR = 1.09; 95% CI: 0.92, 1.30; ER- breast cancer HR = 1.14; 95% CI: 0.81, 1.61; each in the top exposure quartile compared to the lowest). Exposures to HAPs during adulthood were not consistently associated with an increased risk of overall or estrogen-receptor subtypes of invasive breast cancer in this nationwide cohort of women.

Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women.

PubMed

Hirose, Kaoru; Toyama, Tatsuya; Iwata, Hiroji; Takezaki, Toshiro; Hamajima, Nobuyuki; Tajima, Kazuo

2003-01-01

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors (IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein-3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in breast cancer development and interaction of IGF systems.

A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers.

PubMed

Ding, Yuan C; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Paluch-Shimon, Shani-; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M; de Lange, Judith L; Meijers-Heijboer, Hanne E J; Oosterwijk, Jan C; van Asperen, Christi J; Gómez García, Encarna B; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B; Easton, Douglas F; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas V O; Ejlertsen, Bent; Johannsson, Oskar T; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y; Gross, Jenny; Ganz, Patricia A; Beattie, Mary S; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E; Weitzel, Jeffrey; Garber, Judy E; Olopade, Olufunmilayo I; Rubinstein, Wendy S; Tung, Nadine; Blum, Joanne L; Narod, Steven A; Brummel, Sean; Gillen, Daniel L; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S; Couch, Fergus J; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H; Loud, Jennifer T; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L

2012-08-01

We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. ©2012 AACR.

Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer

PubMed Central

Guo, Hao; Sutton, Jazmine; Spring, Laura; Faig, Jennifer; Dagogo-Jack, Ibiayi; Battelli, Chiara; Houlihan, Mary Jane; Yeh, Tsai-Chu; Come, Steven E.; Lin, Nancy U.

2016-01-01

Background. Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC). Materials and Methods. A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC. Results. Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23–90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%–5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease. Conclusion. In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging. Implications for Practice: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron

Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.

PubMed

Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo; Jakubowska, Anna; Heikkilä, Päivi; Fagerholm, Rainer; Greco, Dario; Aittomäki, Kristiina; Bojesen, Stig E; Shah, Mitul; Dunning, Alison M; Rhenius, Valerie; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Chang-Claude, Jenny; Rudolph, Anja; Nordestgaard, Børge G; Couch, Fergus J; Hart, Steven N; Figueroa, Jonine; García-Closas, Montserrat; Fasching, Peter A; Beckmann, Matthias W; Li, Jingmei; Liu, Jianjun; Andrulis, Irene L; Winqvist, Robert; Pylkäs, Katri; Mannermaa, Arto; Kataja, Vesa; Lindblom, Annika; Margolin, Sara; Lubinski, Jan; Dubrowinskaja, Natalia; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F; Pharoah, Paul D P; Schmidt, Marjanka K; Nevanlinna, Heli

2016-10-03

P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly

The "El Alamo" project (1990-1997): two consecutive hospital-based studies of breast cancer outcomes in Spain.

PubMed

Martín, M; Mahillo, E; Llombart-Cussac, A; Lluch, A; Munarriz, B; Pastor, M; Alba, E; Ruiz, A; Antón, A; Bermejo, B

2006-07-01

The "Alamo" project is a retrospective analysis of 14,854 patients diagnosed of breast cancer between 1990 and 1997 in 50 Spanish hospitals. Alamo I (AI) consisted of 4,532 patients diagnosed with breast cancer between 1990 and 1993. Data were collected in 2000. Alamo II (AII) consisted of 10,322 patients diagnosed between 1994 and 1997. Data were collected in 2003. At presentation, there were (AI vs. AII) 17.6% vs. 24.3% at stage I; 55.5% vs. 53.1% at stage II; 18.7% vs. 15% at stage III; 7.2% vs. 5.9 at stage IV. Median age was 57 (AI) vs. 58 years (AII) and 65.9% vs. 67.2% (AI vs. AII) were post-menopausal. Firstline treatment for disease stages I, II and III was surgery in 91% of patients in both studies. Breast conserving surgery rate increased from 20.2% (AI) to 32.7% (AII). Adjuvant systemic treatments were administered to 87.6% (AI) and 92.8% (AII) of patients. Recurrence rate diminished from 36.6% (AI) to 22.5% (AII) and the 9-year survival rate increased from 63.2% (95% CI: 61.5-64.9) to 70.1% (95% CI: 68.5-71.8). Breast cancer outcomes in Spain have improved from 1990-1993 to 1994-1997, likely because of breast cancer screening program implementation and new therapies.

New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

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

Niwinska, Anna, E-mail: alphaonetau@poczta.onet.pl; Murawska, Magdalena

2012-04-01

Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4more » months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of {<=}60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.« less

Outdoor Light at Night and Breast Cancer Incidence in the Nurses’ Health Study II

PubMed Central

Bertrand, Kimberly A.; Hart, Jaime E.; Schernhammer, Eva S.; Tamimi, Rulla M.; Laden, Francine

2017-01-01

Background: Animal and epidemiologic studies suggest that exposure to light at night (LAN) may disrupt circadian patterns and decrease nocturnal secretion of melatonin, which may disturb estrogen regulation, leading to increased breast cancer risk. Objectives: We examined the association between residential outdoor LAN and breast cancer incidence using data from the nationwide U.S.-based Nurses’ Health Study II cohort. Methods: We followed 109,672 women from 1989 through 2013. Cumulative LAN exposure was estimated using time-varying satellite data for a composite of persistent nighttime illumination at ∼1 km2 scale for each residence during follow-up. Incident invasive breast cancer cases were confirmed by medical record review. We used Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for anthropometric, reproductive, lifestyle, and socioeconomic risk factors. Results: Over 2,187,425 person-years, we identified 3,549 incident breast cancer cases. Based on a fully adjusted model, the estimated HR for incident breast cancer with an interquartile range (IQR) (31.6 nW/cm2/sr) increase in cumulative average outdoor LAN was 1.05 (95% CI: 1.00, 1.11). An association between LAN and breast cancer appeared to be limited to women who were premenopausal at the time of a case [HR=1.07 (95% CI: 1.01, 1.14) based on 1,973 cases vs. HR=1.00 (95% CI: 0.91, 1.09) based on 1,172 cases in postmenopausal women; p-interaction=0.08]. The LAN–breast cancer association was observed only in past and current smokers at the end of follow-up [HR=1.00 (95% CI: 0.94, 1.07) based on 2,215 cases in never smokers; HR=1.10 (95% CI: 1.01, 1.19) based on 1,034 cases in past smokers vs. HR=1.21 (95% CI: 1.07, 1.37) for 300 cases in current smokers; p-interaction=0.08]. Conclusions: Although further work is required to confirm our results and to clarify potential mechanisms, our findings suggest that exposure to residential outdoor

Ginseng in Decreasing Cancer-Related Fatigue After Treatment in Cancer Survivors

ClinicalTrials.gov

2018-03-15

Cancer Survivor; Stage I Breast Cancer AJCC v7; Stage I Colon Cancer AJCC v6 and v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage II Colon Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIA Colon Cancer AJCC v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIB Colon Cancer AJCC v7; Stage IIC Colon Cancer AJCC v7; Stage III Breast Cancer AJCC v7; Stage III Colon Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7

Preparation and preclinical evaluation of 131 I-trastuzumab for breast cancer.

PubMed

Kameswaran, Mythili; Gota, Vikram; Ambade, Rajwardhan; Gupta, Sudeep; Dash, Ashutosh

2017-01-01

Trastuzumab that targets the human epidermal growth factor receptor type 2 (HER2) is known to benefit patients with HER2+ metastatic breast cancer. The objective was to explore the potential of 131 I-trastuzumab for treatment of breast cancers. Radioiodination of trastuzumab was carried out by chloramine-T method, purified by using PD-10 column, and characterized by size exclusion high-performance liquid chromatography on a gel column. In vitro studies were carried out in HER2+ cells to determine the specificity of the radioimmunoconjugate. Uptake and retention of 131 I-trastuzumab were determined by biodistribution studies in tumor-bearing non-obese diabetic/severe combined immunodeficiency and normal severe combined immunodeficiency mice. The radiochemical purity (RCP) of 131 I-trastuzumab was 98 ± 0.4% with retention time of 17 minutes by high-performance liquid chromatography. In vitro stability studies exhibited RCP of more than 90% in serum at 37°C after 120 hours of radioiodination. In vitro cell binding with 131 I-trastuzumab in HER2+ cells showed binding of 28% to 35% which was inhibited significantly, with unlabeled trastuzumab confirming its specificity. K d value of 131 I-trastuzumab was 0.5 nM, while its immunoreactivity was more than 80%. Uptake of more than 12% and retention were observed in the tumors up to 120 hours p.i. 131 I-trastuzumab prepared in-house-exhibited RCP of more than 98%, excellent immunoreactivity, affinity to HER2+ cell lines and good tumor uptake thereby indicating its potential for further evaluation in HER2+ breast cancers. Copyright © 2016 John Wiley & Sons, Ltd.

Type I and II Endometrial Cancers: Have They Different Risk Factors?

PubMed Central

Setiawan, Veronica Wendy; Yang, Hannah P.; Pike, Malcolm C.; McCann, Susan E.; Yu, Herbert; Xiang, Yong-Bing; Wolk, Alicja; Wentzensen, Nicolas; Weiss, Noel S.; Webb, Penelope M.; van den Brandt, Piet A.; van de Vijver, Koen; Thompson, Pamela J.; Strom, Brian L.; Spurdle, Amanda B.; Soslow, Robert A.; Shu, Xiao-ou; Schairer, Catherine; Sacerdote, Carlotta; Rohan, Thomas E.; Robien, Kim; Risch, Harvey A.; Ricceri, Fulvio; Rebbeck, Timothy R.; Rastogi, Radhai; Prescott, Jennifer; Polidoro, Silvia; Park, Yikyung; Olson, Sara H.; Moysich, Kirsten B.; Miller, Anthony B.; McCullough, Marjorie L.; Matsuno, Rayna K.; Magliocco, Anthony M.; Lurie, Galina; Lu, Lingeng; Lissowska, Jolanta; Liang, Xiaolin; Lacey, James V.; Kolonel, Laurence N.; Henderson, Brian E.; Hankinson, Susan E.; Håkansson, Niclas; Goodman, Marc T.; Gaudet, Mia M.; Garcia-Closas, Montserrat; Friedenreich, Christine M.; Freudenheim, Jo L.; Doherty, Jennifer; De Vivo, Immaculata; Courneya, Kerry S.; Cook, Linda S.; Chen, Chu; Cerhan, James R.; Cai, Hui; Brinton, Louise A.; Bernstein, Leslie; Anderson, Kristin E.; Anton-Culver, Hoda; Schouten, Leo J.; Horn-Ross, Pamela L.

2013-01-01

Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. PMID:23733771

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

PubMed Central

2013-01-01

Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report

Parenchymal Texture Analysis in Digital Breast Tomosynthesis for Breast Cancer Risk Estimation: A Preliminary Study

PubMed Central

Kontos, Despina; Bakic, Predrag R.; Carton, Ann-Katherine; Troxel, Andrea B.; Conant, Emily F.; Maidment, Andrew D.A.

2009-01-01

Rationale and Objectives Studies have demonstrated a relationship between mammographic parenchymal texture and breast cancer risk. Although promising, texture analysis in mammograms is limited by tissue superimposition. Digital breast tomosynthesis (DBT) is a novel tomographic x-ray breast imaging modality that alleviates the effect of tissue superimposition, offering superior parenchymal texture visualization compared to mammography. Our study investigates the potential advantages of DBT parenchymal texture analysis for breast cancer risk estimation. Materials and Methods DBT and digital mammography (DM) images of 39 women were analyzed. Texture features, shown in studies with mammograms to correlate with cancer risk, were computed from the retroareolar breast region. We compared the relative performance of DBT and DM texture features in correlating with two measures of breast cancer risk: (i) the Gail and Claus risk estimates, and (ii) mammographic breast density. Linear regression was performed to model the association between texture features and increasing levels of risk. Results No significant correlation was detected between parenchymal texture and the Gail and Claus risk estimates. Significant correlations were observed between texture features and breast density. Overall, the DBT texture features demonstrated stronger correlations with breast percent density (PD) than DM (p ≤0.05). When dividing our study population in groups of increasing breast PD, the DBT texture features appeared to be more discriminative, having regression lines with overall lower p-values, steeper slopes, and higher R2 estimates. Conclusion Although preliminary, our results suggest that DBT parenchymal texture analysis could provide more accurate characterization of breast density patterns, which could ultimately improve breast cancer risk estimation. PMID:19201357

Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

ClinicalTrials.gov

2018-03-30

BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

Metabolic imaging for breast cancer detection and treatment: a role for mitochondrial Complex I function

NASA Astrophysics Data System (ADS)

Ramanujan, V. Krishnan

2018-02-01

Cancer cells are known to display a variety of metabolic reprogramming strategies to fulfill their own growth and proliferative agenda. With the advent of high resolution imaging strategies, metabolomics techniques etc., there is an increasing appreciation of critical role that tumor cell metabolism plays in the overall breast cancer (BC) growth. A recent study from our laboratory demonstrated that the development of invasive cancers could be causally connected to deficits in mitochondrial function. Using this study as a rationale, we hypothesize that the widely accepted multistep tumor growth model might have a strong metabolic component as well. In this study, we explore the possibility of targeting mitochondrial Complex I enzyme system for not only metabolic detection of cancer-associated redox changes but also for modulating breast cancer cell growth characteristics. As a proof-of-principle, we demonstrate two approaches (pharmacological and genetic) for modulating mitochondrial Complex I function so as to achieve breast cancer control.

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.

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

ClinicalTrials.gov

2017-12-07

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

The Nuclear Receptor, RORγ, Regulates Pathways Necessary for Breast Cancer Metastasis

PubMed Central

Oh, Tae Gyu; Wang, Shu-Ching M.; Acharya, Bipul R.; Goode, Joel M.; Graham, J. Dinny; Clarke, Christine L.; Yap, Alpha S.; Muscat, George E.O.

2016-01-01

We have previously reported that RORγ expression was decreased in ER − ve breast cancer, and increased expression improves clinical outcomes. However, the underlying RORγ dependent mechanisms that repress breast carcinogenesis have not been elucidated. Here we report that RORγ negatively regulates the oncogenic TGF-β/EMT and mammary stem cell (MaSC) pathways, whereas RORγ positively regulates DNA-repair. We demonstrate that RORγ expression is: (i) decreased in basal-like subtype cancers, and (ii) inversely correlated with histological grade and drivers of carcinogenesis in breast cancer cohorts. Furthermore, integration of RNA-seq and ChIP-chip data reveals that RORγ regulates the expression of many genes involved in TGF-β/EMT-signaling, DNA-repair and MaSC pathways (including the non-coding RNA, LINC00511). In accordance, pharmacological studies demonstrate that an RORγ agonist suppresses breast cancer cell viability, migration, the EMT transition (microsphere outgrowth) and mammosphere-growth. In contrast, RNA-seq demonstrates an RORγ inverse agonist induces TGF-β/EMT-signaling. These findings suggest pharmacological modulation of RORγ activity may have utility in breast cancer. PMID:27211549

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

ClinicalTrials.gov

2018-02-06

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

Randomized control trial: evaluating aluminum-based antiperspirant use, axilla skin toxicity, and reported quality of life in women receiving external beam radiotherapy for treatment of Stage 0, I, and II breast cancer.

PubMed

Watson, Linda C; Gies, Donna; Thompson, Emmanuel; Thomas, Bejoy

2012-05-01

Standard skin care instructions regarding the use of antiperspirants during radiotherapy to the breast varies across North America. Women have articulated that when instructed to not use antiperspirant, the potential for body odor is distressing. Historical practices and individual opinions have often guided practice in this field. The present study had 2 purposes. To evaluate whether the use of aluminum-based antiperspirant while receiving external beam radiotherapy for stage 0, I, or II breast cancer will increase axilla skin toxicity and to evaluate whether the use of antiperspirant during external beam radiotherapy improves quality of life. A total of 198 participants were randomized to either the experimental group (antiperspirant) or control group (standard care-wash only). The skin reactions in both groups were measured weekly and 2 weeks after treatment using the National Cancer Institute Common Toxicity Criteria Adverse Events, version 3, toxicity grading criteria. Both groups completed the Functional Assessment for Chronic Illness Therapy's questionnaire for the breast population quality of life assessment tool, with additional questions evaluating the effect of underarm antiperspirant use on quality of life before treatment, immediately after treatment, and 2 weeks after treatment during the study. The skin reaction data were analyzed using the generalized estimating equation. No statistically significant difference was seen in the skin reaction between the 2 groups over time. The quality of life data also revealed no statistically significant difference between the 2 groups over time. Data analysis indicates that using antiperspirant routinely during external beam radiotherapy for Stage 0, I, or II breast cancer does not affect the intensity of the skin reaction or the self-reported quality of life. This evidence supports that in this particular population, there is no purpose to restrict these women from using antiperspirants during their treatment

Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses' Health Study II.

PubMed

Fortner, Renée T; Eliassen, A Heather; Spiegelman, Donna; Willett, Walter C; Barbieri, Robert L; Hankinson, Susan E

2013-03-06

Prior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women. We evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses. In analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9), Ptrend = 0.02). Luteal estrone, free estradiol and progesterone were not associated with risk. Androgens were suggestively or significantly associated with risk when the sample was restricted to invasive tumors (for example, testosterone: OR: 1.4 (1.0 to 2.0), Ptrend = 0.23) and ER+/PR+ disease (testosterone: OR: 1.7 (1.1 to 2.6) Ptrend = 0.10; dehydroepiandrosterone sulfate (DHEAS) OR: 1.3 (0.8 to 2.0) Ptrend = 0.05). SHBG was not associated with breast cancer risk. The results varied by menopausal status at diagnosis, with follicular estradiol suggestively positively associated with breast cancers

Dietary pattern and health-related quality of life among breast cancer survivors.

PubMed

Kim, Na-Hui; Song, Sihan; Jung, So-Youn; Lee, Eunsook; Kim, Zisun; Moon, Hyeong-Gon; Noh, Dong-Young; Lee, Jung Eun

2018-05-10

There is limited evidence for the association between dietary pattern and quality of life among breast cancer survivors. We examined the association between dietary patterns and health-related quality of life (HRQoL) among Korean breast cancer survivors. Our study included a total of 232 women, aged 21 to 79 years, who had been diagnosed with stage I to III breast cancer and who underwent breast cancer surgery at least 6 months prior to our baseline evaluation. We assessed HRQoL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23). We conducted a factor analysis to identify the major dietary patterns and used a generalized linear model to obtain the least squares mean (LS mean) and 95% confidence interval (CI) for HRQoL according to the dietary pattern scores. We identified 2 major dietary patterns: the Healthy dietary pattern and the Western dietary pattern. We found that breast cancer survivors who had higher Healthy dietary pattern scores tended to have lower dyspnea scores but higher insomnia scores, compared to breast cancer survivors with lower Healthy dietary pattern scores. For dyspnea, the LS mean (95% CI) was 8.86 (5.05-15.52) in the bottom quartile and 2.87 (1.62-5.08) in the top quartile (p for trend = 0.005). This association was limited to survivors with stage I for dyspnea or survivors with stage II or III for insomnia. Healthy dietary patterns were associated with better scores for dyspnea but worse scores for insomnia among breast cancer survivors. Other components of EORTC QLQ did not vary by dietary patterns overall, but they warrant further investigation for subgroups of breast cancer survivors.

Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women

PubMed Central

2011-01-01

Background Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions. Methods The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested. Results All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences. Conclusions Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women. PMID:21247504

In vivo examination of (188)Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer.

PubMed

Chen, Kuo-Ting; Lee, Te-Wei; Lo, Jem-Mau

2009-05-01

Trastuzumab (Herceptin), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. Radiolabeled trastuzumab with beta- or alpha emitters can be used as radioimmunotherapeutic agent for the similar purpose but with additional radiation effect. In this study, trastuzumab was labeled with (188)Re for radioimmunotherapy of HER2/neu-positive breast cancer. (188)Re(I)-tricarbonyl ion, [(188)Re(OH(2))(3)(CO)(3)](+), was employed as a precursor for directly labeling the monoclonal antibody with (188)Re. The immunoreactivity of (188)Re(I)-trastuzumab was estimated by competition receptor-binding assay using HER2/neu-overexpressive BT-474 human breast cancer cells. The localization properties of (188)Re(I)-trastuzumab within both tumor and normal tissues of athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressive) and similar mice bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressive) were investigated. When incubated with human serum albumin and histidine at 25 degrees C, (188)Re(I)-trastuzumab was found to be stable within 24 h. The IC(50) of (188)Re(I)-trastuzumab was found to be 22.63+/-4.57 nM. (188)Re(I)-trastuzumab was shown to accumulate specifically in BT-474 tumor tissue in in vivo biodistribution studies. By microSPECT/CT, the image of (188)Re localized BT-474 tumor was clearly visualized within 24 h. In contrast, (188)Re(I)-trastuzumab uptake in HER2-low-expressing MCF-7 tumor was minimal, and the (188)Re image at the localization of the tumor was dim. These results reveal that (188)Re(I)-trastuzumab could be an appropriate radioimmunotherapeutic agent for the treatment of HER2/neu-overexpressing cancers.

A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer.

PubMed

Schuler, Martin; Awada, Ahmad; Harter, Philipp; Canon, Jean Luc; Possinger, Kurt; Schmidt, Marcus; De Grève, Jacques; Neven, Patrick; Dirix, Luc; Jonat, Walter; Beckmann, Matthias W; Schütte, Jochen; Fasching, Peter A; Gottschalk, Nina; Besse-Hammer, Tatiana; Fleischer, Frank; Wind, Sven; Uttenreuther-Fischer, Martina; Piccart, Martine; Harbeck, Nadia

2012-08-01

Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in human epidermal growth factor receptor HER2 (ErbB2)-positive and triple-negative xenograft models of breast cancer, and clinical activity in phase I studies. This was a multicenter phase II study enrolling patients with HER2-negative metastatic breast cancer progressing following no more than three lines of chemotherapy. No prior epidermal growth factor receptor-targeted therapy was allowed. Patients received 50-mg afatinib once daily until disease progression. Tumor assessment was performed at every other 28-day treatment course. The primary endpoint was clinical benefit (CB) for ≥4 treatment courses in triple-negative (Cohort A) metastatic breast cancer (TNBC) and objective responses measured by Response Evaluation Criteria in Solid Tumors in patients with HER2-negative, estrogen receptor-positive, and/or progesterone receptor-positive breast cancer (Cohort B). Fifty patients received treatment, including 29 patients in Cohort A and 21 patients in Cohort B. No objective responses were observed in either cohort. Median progression-free survival was 7.4 and 7.7 weeks in Cohorts A and B, respectively. Three patients with TNBC had stable disease for ≥4 treatment courses, one of them for 12 courses (median 26.3 weeks; range 18.9-47.9 weeks). The most frequently observed afatinib-associated adverse events (AEs) were gastrointestinal and skin-related side effects, which were manageable by symptomatic treatment and dose reductions. Afatinib pharmacokinetics were comparable to those observed in previously reported phase I trials. In conclusion, afatinib had limited activity in HER2-negative breast cancer. AEs were generally manageable and mainly affected the skin and the gastrointestinal tract.

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

ClinicalTrials.gov

2018-06-08

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

Influence of previous breast surgery in sentinel lymph node biopsy in patients with breast cancer.

PubMed

López-Prior, V; Díaz-Expósito, R; Casáns Tormo, I

The aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection. A retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables. The overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II). Sentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Five-Year Risk of Interval-Invasive Second Breast Cancer

PubMed Central

Buist, Diana S. M.; Houssami, Nehmat; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott; Lehman, Constance D.; Henderson, Louise M.; Hubbard, Rebecca A.

2015-01-01

Background: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. Methods: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. Results: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. Conclusions: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. PMID:25904721

Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

PubMed Central

Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Steinmaus, Craig; Liaw, Jane; Smith, Martyn T.; Wood, Lily; Heirich, Marissa; Fritzemeier, Rebecca M.; Pegram, Mark D.; Ferreccio, Catterina

2014-01-01

Background Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970. Methods We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies. Findings Before 1958, breast cancer mortality rates were similar, but in 1958–1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51, 95% CI 0.40–0.66; p < 0.0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965–1970 (RR = 0.30, 0.17–0.54; p < 0.0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II. Interpretation We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer. PMID:25580451

Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

DTIC Science & Technology

2015-10-01

including antigens preferentially expressed by breast cancer stem cells. We will identify both MHC-I- and MHC-II- restricted antigens driving both CD8...even two of them were exclusively targeted by T cells in chronic lymphocytic leukemia ( CLL ) patients (3). This analysis demonstrated both that...lymphocytic leukemia ( CLL ) 7 positive CLLs (23%) 3 Table 1. Immunogenic peptides that have been eluted from the cell surface of breast carcinoma cells

Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study.

PubMed

Parada, Humberto; Sun, Xuezheng; Tse, Chiu-Kit; Olshan, Andrew F; Troester, Melissa A; Conway, Kathleen

2017-09-01

To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study. We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.56 years, we identified 717 deaths using the National Death Index; 427 were breast cancer-related. We used Cox regression to examine associations between self-reported measures of smoking and breast cancer-specific survival within 5 years and up to 18 years after diagnosis conditional on 5-year survival. We examined race and estrogen receptor status as potential modifiers. Current (vs never) smoking was not associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI 1.06-2.25), compared to never smokers. Although smoking rates were similar among African American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific mortality was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs. never) smokers (P Interaction  = 0.30). Risk of breast cancer-specific mortality was also elevated among current (vs never) smokers diagnosed with ER - (HR 2.58, 95% CI 1.35-4.93), but not ER + (HR 1.11, 95% CI 0.69-1.78) tumors (P Interaction  = 0.17). Smoking may negatively impact long-term survival following breast cancer. Racial differences in long-term survival, as related to smoking, may be driven by ER status, rather than by differences in smoking patterns.

Nation-Wide Korean Breast Cancer Data from 2008 Using the Breast Cancer Registration Program

PubMed Central

Na, Kuk Young; Kim, Ku Sang; Ahn, Sei-Hyun; Lee, Soo-Joong; Park, Heung Kyu; Cho, Young Up

2011-01-01

Purpose Since 1996, the Korean Breast Cancer Society has collected nation-wide breast cancer data and analyzed the data using their online registration program biannually. The purpose of this study was to evaluate the characteristics of Korean breast cancer from 2008 and examine chronological based patterns. Methods Data were collected from 38 medical schools (67 hospitals), 20 general hospitals, and 10 private clinics. The data on the total number, gender, and age distribution were collected through a questionnaire as well as other detailed data analyzed via the online registration program. Results In 2008, there were 13,908 patients who were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 57.3 among 100,000 and the median age was 49 years. The age distribution had not changed since the initial survey; however the proportion of postmenopausal patients had increased and median age was older than the past. In staging distribution, the proportion of early breast cancer (stage 0, I) was 47.2% with, breast-conserving surgery performed in 58% and mastectomy in 39.5%. Conclusion Compared to past data, the incidence of breast cancer in Korea continues to rise. Furthermore, the proportion of those detected by screening and breast conservation surgery has increased remarkably. To understand the patterns of Korean breast cancer, the nation-wide data should continuously investigated. PMID:22031806

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer.

PubMed

Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M; Reddy, Srinivasa T; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

2016-11-03

Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

PubMed Central

Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

2016-01-01

Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

Prevalence of ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms in Brazilian breast cancer-unaffected women

PubMed Central

Giacomazzi, J.; Aguiar, E.; Palmero, E.I.; Schmidt, A.V.; Skonieski, G.; Filho, D.D.; Bock, H.; Saraiva-Pereira, M.L.; Ewald, I.P.; Schuler-Faccini, L.; Camey, S.A.; Caleffi, M.; Giugliani, R.; Ashton-Prolla, P.

2012-01-01

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease. PMID:22584640

Breast cancer treatment and ethnicity in British Columbia, Canada

PubMed Central

2010-01-01

Background Racial and ethnic disparities in breast cancer incidence, stage at diagnosis, survival and mortality are well documented; but few studies have reported on disparities in breast cancer treatment. This paper compares the treatment received by breast cancer patients in British Columbia (BC) for three ethnic groups and three time periods. Values for breast cancer treatments received in the BC general population are provided for reference. Methods Information on patients, tumour characteristics and treatment was obtained from BC Cancer Registry (BCCR) and BC Cancer Agency (BCCA) records. Treatment among ethnic groups was analyzed by stage at diagnosis and time period at diagnosis. Differences among the three ethnic groups were tested using chi-square tests, Fisher exact tests and a multivariate logistic model. Results There was no significant difference in overall surgery use for stage I and II disease between the ethnic groups, however there were significant differences when surgery with and without radiation were considered separately. These differences did not change significantly with time. Treatment with chemotherapy and hormone therapy did not differ among the minority groups. Conclusion The description of treatment differences is the first step to guiding interventions that reduce ethnic disparities. Specific studies need to examine reasons for the observed differences and the influence of culture and beliefs. PMID:20406489

Modeling Malignant Breast Cancer Occurrence and Survival in Black and White Women

ERIC Educational Resources Information Center

Gleason, Michael

2013-01-01

Background: Breast cancer (BC), the most common cancer diagnosed in women in the United States, is a heterogeneous disease in which age-specific incidence rates (ASIRs) differ by race and mortality rates are higher in blacks than whites. Goals: (i) understand the reasons for the black-to-white ethnic crossover in the ASIRs; (ii) formulate a…

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.

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

ClinicalTrials.gov

2018-01-09

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

Reference frameworks for the health management of measles, breast cancer and diabetes (type II).

PubMed

Brand, Helmut; Schröder, Peter; Davies, John K; Escamilla, Ixhel; Hall, Caroline; Hickey, Kieran; Jelastopulu, Eleni; Mechtler, Reli; Yared, Wendy Tse; Volf, Jaroslav; Weihrauch, Birgit

2006-03-01

This paper presents reference frameworks which order effective and feasible policies and interventions for the health management of measles, breast cancer and diabetes (type II). These reference frameworks can be used to rapidly appraise regional health policy documents and existing health management systems. Furthermore, the reference frameworks can serve health policy makers for the planning of health management measures.

Receipt of Guideline-Concordant Care Among Older Women With Stage I-III Breast Cancer: A Population-Based Study.

PubMed

LeMasters, Traci; Madhavan, S Suresh; Sambamoorthi, Usha; Hazard-Jenkins, Hannah W; Kelly, Kimberly M; Long, Dustin

2018-06-01

Background: This study examined receipt of guideline-concordant care (GCC) according to evidence-based treatment guidelines and quality measures and specific types of treatment among older women with breast cancer. Patients and Methods: A total of 142,433 patients aged ≥66 years diagnosed with stage I-III breast cancer between 2007 and 2011 were identified in the SEER-Medicare linked database. Algorithms considering cancer characteristics and the appropriate course of care as per guidelines versus actual care received determined receipt of GCC. Multivariable logistic regression estimated the likelihood of GCC and specific types of treatment for women aged ≥75 versus 66 to 74 years. Results: Overall, 39.7% of patients received GCC. Patients diagnosed at stage II or III, with certain preexisting conditions, and of nonwhite race were less likely to receive GCC. Patients with hormone-negative tumors, higher grade tumors, and greater access to oncology care resources were more likely to receive GCC. Patients aged ≥75 years were approximately 40% less likely to receive GCC or adjuvant endocrine therapy, 78% less likely to have any surgery, 61% less likely to have chemotherapy, and about half as likely to have radiation therapy than those aged 66 to 74 years. Conclusions: Fewer than half of older women with breast cancer received GCC, with the lowest rates observed among the oldest age groups, racial/ethnic minorities, and women with later-stage cancers. However, patients with more aggressive tumor characteristics and greater access to oncology resources were more likely to receive GCC. Considering that older women have the highest incidence of breast cancer and that many are diagnosed at stages requiring more aggressive treatment, efforts to increase rates of earlier stage diagnosis and the development of less toxic treatments could help improve GCC and survival while preserving quality of life. Copyright © 2018 by the National Comprehensive Cancer Network.

DNA Topoisomerase I-Targeted Therapy for Breast Cancer

DTIC Science & Technology

1997-06-01

Fort Detrick, Frederick, MD 21702-5012. 13. ABSTRACT (Maximum 200 words] Camptothecin analogues have been developed that show enhanced pre-clinical...activity against breast cancer cells. These analogues have been synthesized with two fundamental modifications that aid in their effectiveness against...activity. The new analogues , in both growth inhibition and clonogenic assays, are substantially more effective against breast cancer cells than those

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Papilloma Virus Identification in Breast Cancer Patients with Previous Cervical Neoplasia.

PubMed

Lawson, James S; Glenn, Wendy K; Salyakina, Daria; Clay, Rosemary; Delprado, Warick; Cheerala, Bharathi; Tran, Dinh D; Ngan, Christopher C; Miyauchi, Shingo; Karim, Martha; Antonsson, Annika; Whitaker, Noel J

2015-01-01

Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

PubMed

Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

2015-05-01

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

The Nuclear Receptor, RORγ, Regulates Pathways Necessary for Breast Cancer Metastasis.

PubMed

Oh, Tae Gyu; Wang, Shu-Ching M; Acharya, Bipul R; Goode, Joel M; Graham, J Dinny; Clarke, Christine L; Yap, Alpha S; Muscat, George E O

2016-04-01

We have previously reported that RORγ expression was decreased in ER-ve breast cancer, and increased expression improves clinical outcomes. However, the underlying RORγ dependent mechanisms that repress breast carcinogenesis have not been elucidated. Here we report that RORγ negatively regulates the oncogenic TGF-β/EMT and mammary stem cell (MaSC) pathways, whereas RORγ positively regulates DNA-repair. We demonstrate that RORγ expression is: (i) decreased in basal-like subtype cancers, and (ii) inversely correlated with histological grade and drivers of carcinogenesis in breast cancer cohorts. Furthermore, integration of RNA-seq and ChIP-chip data reveals that RORγ regulates the expression of many genes involved in TGF-β/EMT-signaling, DNA-repair and MaSC pathways (including the non-coding RNA, LINC00511). In accordance, pharmacological studies demonstrate that an RORγ agonist suppresses breast cancer cell viability, migration, the EMT transition (microsphere outgrowth) and mammosphere-growth. In contrast, RNA-seq demonstrates an RORγ inverse agonist induces TGF-β/EMT-signaling. These findings suggest pharmacological modulation of RORγ activity may have utility in breast cancer. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Choosing wisely after publication of level I evidence in breast cancer radiotherapy.

PubMed

Niska, Joshua R; Keole, Sameer R; Pockaj, Barbara A; Halyard, Michele Y; Patel, Samir H; Northfelt, Donald W; Gray, Richard J; Wasif, Nabil; Vargas, Carlos E; Wong, William W

2018-01-01

Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT. To assess response to level I evidence and adherence to ASTRO recommendations, we evaluated the pattern of RT use for early-stage breast cancer at our National Comprehensive Cancer Network institution from 2006 to 2008 and 2011 to 2013 and compared the results with national trends. Data from a prospective database were extracted to include patients treated with BCT, aged ≥50 years, with histologic findings of invasive ductal carcinoma, stage T1-T2N0M0, estrogen receptor-positive, and HER2 normal. We retrospectively reviewed the medical records and estimated costs based on 2016 Hospital Outpatient Prospective Payment System (technical fees) and Medicare Physician Fee Schedule (professional fees). Among 55 cases from 2006 to 2008, treatment regimens were 11% hypofractionated, 69% traditional schedule, and 20% RT omission (29% of patients were aged >70 years). Among 83 cases from 2011 to 2013, treatment regimens were 54% hypofractionated, 19% traditional schedule, and 27% RT omission (48% of patients were aged >70 years). 3DCRT was used for all WBRT treatments. Direct medical cost estimates were as follows: 15 fractions 3DCRT, $7,197.87; 15 fractions IMRT, $11,232.33; 25 fractions 3DCRT, $9,731.39; and 25 fractions IMRT, $16,877.45. Despite apparent resistance to shorter radiation schedules in the United States, we demonstrate that rapid practice change in response to level I

Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.

2012-11-01

Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.

Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

PubMed

Jung, Hyun Ae; Park, Yeon Hee; Kim, Moonjin; Kim, Sungmin; Chang, Won Jin; Choi, Moon Ki; Hong, Jung Yong; Kim, Seok Won; Kil, Won Ho; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck

2015-02-01

Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I-III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4%) patients were stage I, and 682 (59.6%) were stage II or III. In addition, 701 (61.2%) patients were HR positive, 239 (20.9%) were HER2 positive, and 205 (20.9%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0-25%) was 99%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83%, respectively (P value = <0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92%, P value = 0.011) and OS (99 versus 96%, P value = 0.03) at 5 years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I-III breast cancer who show

Conservative treatment for breast cancer. Complications requiring reconstructive surgery

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

Bostwick, J. 3d.; Paletta, C.; Hartrampf, C.R.

Women who select conservative treatment for carcinoma of the breast (tumor excision followed by supervoltage radiation therapy) place a premium on breast preservation and aesthetics. When local control fails and they require a mastectomy, or when the aesthetic appearance is unacceptable, they may request breast reconstruction. The goal of this study is to evaluate a series of 10 patients who required reconstructive breast surgery after complications of conservative treatment. Patient classification: I. Breast or chest wall necrosis (3). II. Breast fibrosis and gross asymmetry (3). III. Local recurrence of breast cancer (5). IV. Positive margins after the initial lumpectomy (1).more » The mean age was 34 years. Radiation dosage average was 5252 rads with two patients receiving iridium-192 implant boosts. The reconstructive management was complex and usually required a major musculocutaneous flap because of the radiation effects.« less

Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

PubMed

Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

2017-06-01

Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density. Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1 st -degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density. Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density. Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history. Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR . ©2017 American Association for Cancer Research.

Investigation of VOCs associated with different characteristics of breast cancer cells

PubMed Central

Lavra, Luca; Catini, Alexandro; Ulivieri, Alessandra; Capuano, Rosamaria; Baghernajad Salehi, Leila; Sciacchitano, Salvatore; Bartolazzi, Armando; Nardis, Sara; Paolesse, Roberto; Martinelli, Eugenio; Di Natale, Corrado

2015-01-01

The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization. PMID:26304457

Nutritional channels in breast cancer.

PubMed

Godoy, Alejandro; Salazar, Katherine; Figueroa, Carlos; Smith, Gary J; de Los Angeles Garcia, Maria; Nualart, Francisco J

2009-09-01

Breast cancers increase glucose uptake by increasing expression of the facilitative glucose transporters (GLUTs), mainly GLUT1. However, little is known about the relationship between GLUT1 expression and malignant potential in breast cancer. In this study, expression and subcellular localization of GLUT1 was analysed in vivo in breast cancer tissue specimens with differing malignant potential, based on the Scarff-Bloom-Richardson (SBRI, II, III) histological grading system, and in vitro in the breast cancer cell lines, MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts in nude athymic BALB/c male mice. In situ hybridization analyses demonstrated similar levels of GLUT1 mRNA expression in tissue sections from breast cancers of all histological grades. However, GLUT1 protein was expressed at higher levels in grade SBRII cancer, compared with SBRI and SBRIII, and associated with the expression of the proliferation marker PCNA. Immunolocalization analyses in SBRII cancers demonstrated a preferential localization of GLUT1 to the portions of the cellular membrane that faced neighbouring cells and formed 'canaliculi-like structures', that we hypothesize could have a potential role as 'nutritional channels'. A similar pattern of GLUT1 localization was observed in confluent cultures of MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts, but not in the normal breast epithelial cell line HMEC. However, no relationship between GLUT1 expression and malignant potential of human breast cancer was observed. Preferential subcellular localization of GLUT1 could represent a physiological adaptation of a subset of breast cancer cells that form infiltrative tumours with a nodular growth pattern and that therefore need a major diffusion of glucose from blood vessels.

Five-year risk of interval-invasive second breast cancer.

PubMed

Lee, Janie M; Buist, Diana S M; Houssami, Nehmat; Dowling, Emily C; Halpern, Elkan F; Gazelle, G Scott; Lehman, Constance D; Henderson, Louise M; Hubbard, Rebecca A

2015-07-01

Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. © The Author 2015. Published by Oxford University Press. All rights reserved

Adolescent meat intake and breast cancer risk

PubMed Central

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

2015-01-01

The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of adolescent total red meat was significantly associated with higher premenopausal breast cancer risk (highest vs lowest quintiles, RR, 1.42; 95%CI, 1.05-1.94; Ptrend=0.007), but not postmenopausal breast cancer. Adolescent poultry intake was associated with lower risk of breast cancer overall (RR, 0.75; 95%CI, 0.59-0.96; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 16% lower risk of breast cancer overall (RR, 0.84; 95%CI, 0.74-0.96) and a 24% lower risk of premenopausal breast cancer (RR, 0.76; 95%CI, 0.64-0.92). Higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. PMID:25220168

Selection of high risk groups among prognostically favorable patients with breast cancer.

PubMed Central

Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

1981-01-01

In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

PubMed

Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

2017-07-01

Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

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

PubMed

Pieters, Huibrie C

2016-01-01

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

Lymphatic and blood vessels in male breast cancer.

PubMed

Niemiec, Joanna; Sas-Korczynska, Beata; Harazin-Lechowska, Agnieszka; Martynow, Dariusz; Adamczyk, Agnieszka

2015-02-01

It is assumed that lymphatic vessels are responsible for breast cancer dissemination. In 32 male breast carcinomas we evaluated the correlation between: (i) lymphatic vessel density (LVD), distribution of podoplanin-immunostained vessels (DPV), blood vessel density (BVD), infiltration of immune cells and (ii) known clinicopathological parameters. Lymphatic and blood vessels were found in 77.8% and 100% of breast carcinomas, respectively. Double-negative estrogen and progesterone receptor tumors (ER-/PR-) presented significantly higher LVD than ER/PR positive cases, while high-grade tumors exhibited significantly higher DPV than low-grade carcinomas. We detected significantly higher frequency of vascular invasion in high-grade and double-negative carcinomas than in low-grade and ER/PR-positive ones, respectively. The relationship between high number of lymphatic vessels and high tumor grade or steroid receptor negativity might confirm the hypothesis regarding the influence of lymphangiogenesis on the formation of a more aggressive phenotype in male breast cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

NASA Astrophysics Data System (ADS)

Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

2017-09-01

The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

Multiple biomarkers in molecular oncology. II. Molecular diagnostics applications in breast cancer management.

PubMed

Malinowski, Douglas P

2007-05-01

In recent years, the application of genomic and proteomic technologies to the problem of breast cancer prognosis and the prediction of therapy response have begun to yield encouraging results. Independent studies employing transcriptional profiling of primary breast cancer specimens using DNA microarrays have identified gene expression profiles that correlate with clinical outcome in primary breast biopsy specimens. Recent advances in microarray technology have demonstrated reproducibility, making clinical applications more achievable. In this regard, one such DNA microarray device based upon a 70-gene expression signature was recently cleared by the US FDA for application to breast cancer prognosis. These DNA microarrays often employ at least 70 gene targets for transcriptional profiling and prognostic assessment in breast cancer. The use of PCR-based methods utilizing a small subset of genes has recently demonstrated the ability to predict the clinical outcome in early-stage breast cancer. Furthermore, protein-based immunohistochemistry methods have progressed from using gene clusters and gene expression profiling to smaller subsets of expressed proteins to predict prognosis in early-stage breast cancer. Beyond prognostic applications, DNA microarray-based transcriptional profiling has demonstrated the ability to predict response to chemotherapy in early-stage breast cancer patients. In this review, recent advances in the use of multiple markers for prognosis of disease recurrence in early-stage breast cancer and the prediction of therapy response will be discussed.

[Clinicopathological analyses of accessory breast cancer: a report of 22 cases].

PubMed

Wang, Haotian; Duan, Jingjing; Xin, Fei; Cao, Xuchen

2015-01-27

To explore the clinicopathological characteristics, diagnosis, multi-disciplinary therapy and prognosis of accessory breast cancer. The clinical data were retrospectively analyzed for 22 patients with accessory breast cancer from December 2000 and September 2013. Three patients underwent breast-conserving local wide excision of tumor plus axillary lymph node dissection while the remainder had Auchincloss or Halsted mastectomy. The most common histological type was infiltrating ductal carcinoma (n = 16, 72%) and one of them was associated with mucous adenocarcinoma. There were carcinoma simplex (n = 1), papillary adenocarcinoma (n = 1) and adenocarcinoma (n = 4). The most common pathological stages (according to AJCC Staging of Breast Cancer, 2002, 6th edition) were II (n = 15, 68%),I(n = 3), III (n = 4) and IV (n = 0). The median follow-up period was 3 (1-14) years. And the follow-up rate was 100%.Until October 2014, 2 patients died from metastasis and the remainder survived. Accessory breast cancer is rare and has a worse prognosis.Now the clinical diagnostic criteria to it remains controversial and the diagnosis is often late. A definite diagnosis is made on the basis of clinical characteristics, postoperative pathology and imaging examinations. And surgery remains a major option.

Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

PubMed

Wilson, Sheridan; Speers, Caroline; Tyldesley, Scott; Chia, Stephen; Kennecke, Hagen; Ellard, Susan; Lohrisch, Caroline

2016-08-01

Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged < 50 years with stage I, II, and III disease was 94.8% (95% CI, 92.8%-96.3%), 88.3% (95% CI, 86.0%-90.2%), and 80.4% (95% CI, 73.6%-85.6%), respectively. Among women aged ≥ 50 years, the corresponding EFS rates were 94.8% (95% CI, 93.8%-95.6%), 86.3% (95% CI, 85.0%-87.5%), and 73.8% (95% CI, 69.1%-77.8%). EFS varied significantly by grade. The 10-year recurrence risk was < 10% with stage I cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive Adaptation Theory and Breast Cancer Recurrence: Are There Limits?

ERIC Educational Resources Information Center

Tomich, Patricia L.; Helgeson, Vicki S.

2006-01-01

Relations of the components of cognitive adaptation theory (self-esteem, optimism, control) to quality of life and benefit finding were examined for 70 women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5 years ago. Half of these women experienced a recurrence within the 5 years; the other half remained disease free. Women…

Breast Cancer: Pros and Cons of Conservative vs Aggressive Management

PubMed Central

Davidson, Arthur T.

1981-01-01

Cancer of the breast is the leading type of cancer in women in the United States (28 percent), and the leading cause of death from cancer in women (20 percent). More than half of the cases of breast cancer can be anticipated to exhibit recurrent disease. Most deaths occur within five years of discovery. There has been a minimum reduction in the mortality rate in the past 35 years. This failure is due to microemboli that spread via both the lymphatic and vascular systems in the early predetection state of the primary lesion. In Stage I and Stage II disease, modified radical mastectomy is the treatment of choice. In Stage III disease, radical mastectomy gives a higher incidence of local control of the disease without an increased chance of survival. Adjuvant chemotherapy offers a definite improvement in survival rates. PMID:7031277

Adolescent meat intake and breast cancer risk.

PubMed

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

2015-04-15

The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of total red meat in adolescence was significantly associated with higher premenopausal breast cancer risk (highest vs. lowest quintiles, RR, 1.43; 95%CI, 1.05-1.94; Ptrend  = 0.007), but not postmenopausal breast cancer. Adolescent intake of poultry was associated with lower risk of breast cancer overall (RR, 0.76; 95%CI, 0.60-0.97; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 15% lower risk of breast cancer overall (RR, 0.85; 95%CI, 0.74-0.96) and a 23% lower risk of premenopausal breast cancer (RR, 0.77; 95%CI, 0.64-0.92). In conclusion, higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. © 2014 UICC.

Adaptive Randomization of Neratinib in Early Breast Cancer

PubMed Central

Park, John W.; Liu, Minetta C.; Yee, Douglas; Yau, Christina; van 't Veer, Laura J.; Symmans, W. Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M.; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B.; Chien, A. Jo; Wallace, Anne M.; Boughey, Judy C.; Haddad, Tufia C.; Chui, Stephen Y.; Kemmer, Kathleen A.; Kaplan, Henry G.; Liu, Minetta C.; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S.; Edmiston, Kirsten K.; Elias, Anthony D.; Northfelt, Donald W.; Pusztai, Lajos; Moulder, Stacy L.; Lang, Julie E.; Viscusi, Rebecca K.; Euhus, David M.; Haley, Barbara B.; Khan, Qamar J.; Wood, William C.; Melisko, Michelle; Schwab, Richard; Lyandres, Julia; Davis, Sarah E.; Hirst, Gillian L.; Sanil, Ashish; Esserman, Laura J.; Berry, Donald A.

2017-01-01

Background I-SPY2, a standing, multicenter, adaptive phase 2 neoadjuvant trial ongoing in high-risk clinical stage II/III breast cancer, is designed to evaluate multiple, novel experimental agents added to standard chemotherapy for their ability to improve the rate of pathologic complete response (pCR). Experimental therapies are compared against a common control arm. We report efficacy for the tyrosine kinase inhibitor neratinib. Methods Eligible women had ≥2.5 cm stage II/III breast cancer, categorized into 8 biomarker subtypes based on HER2, hormone-receptor status (HR), and MammaPrint. Neratinib was evaluated for 10 signatures (prospectively defined subtype combinations), with primary endpoint pCR. MR volume changes inform likelihood of pCR for each patient prior to surgery. Adaptive assignment to experimental arms within disease subtype was based on current Bayesian probabilities of superiority over control. Accrual to experimental arm stop at any time for futility or graduation within a particular signature based on Bayesian predictive probability of success in a confirmatory trial. The maximum sample size in any experimental arm is 120 patients, Results With 115 patients and 78 concurrently randomized controls, neratinib graduated in the HER2+/HR− signature, with mean pCR rate 56% (95% PI: 37 to 73%) vs 33% for controls (11 to 54%). Final predictive probability of success, updated when all pathology data were available, was 79%. Conclusion Adaptive, multi-armed trials can efficiently identify responding tumor subtypes. Neratinib added to standard therapy is highly likely to improve pCR rates in HER2+/HR2212; breast cancer. Confirmation in I-SPY 3, a phase 3 neoadjuvant registration trial, is planned. PMID:27406346

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Synthesis, characterization and biological activities of some Ru(II) complexes with substituted chalcones and their applications as chemotherapeutics against breast cancer

NASA Astrophysics Data System (ADS)

Singh, Ashok K.; Saxena, Gunjan; Dixit, Shivani; Hamidullah; Singh, Sachin K.; Singh, Sudheer K.; Arshad, M.; Konwar, Rituraj

2016-05-01

Four new Ru(II) DMSO complexes with substituted chalcone ligands viz. (E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (HL1), (E)-1-(2-hydroxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HL2), (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (HL3) and (E)-1-(2-hydroxyphenyl)-3-(4-Chlorophenyl)prop-2-en-1-one (HL4) have been synthesized, and characterized by micro-analyses, IR, 1H NMR, UV-Vis and ESI-MS and screened for anti-cancer activity against breast cancer cell lines (MCF-7 and MDA MB-231). Compounds HL4 and [Ru(HL1) (O-DMSO)3(S-DMSO)]Cl (M1R) showed significant anti-breast cancer activity as evident from cytotoxicity, morphological and nuclear changes, DNA fragmentation and cell cycle arrest in breast cancer cells. UV-Vis and CD-spectra analysis showed HL4 and M1R interfered with DNA absorption spectra possibly due to DNA binding whereas these compounds were devoid of DNA topoisomerase inhibiting activity. Thus, these Ru(II) compounds have been established as new leads for future optimization by improving anti-cancer potency and safety.

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.

PubMed

Carriere, Patrick P; Llopis, Shawn D; Naiki, Anna C; Nguyen, Gina; Phan, Tina; Nguyen, Mary M; Preyan, Lynez C; Yearby, Letitia; Pratt, Jamal; Burks, Hope; Davenport, Ian R; Nguyen, Thu A; Parker-Lemieux, KiTani; Payton-Stewart, Florastina; Williams, Christopher C; Boué, Stephen M; Burow, Matthew E; Collins-Burow, Bridgette; Hilliard, Aaron; Davidson, A Michael; Tilghman, Syreeta L

2015-12-22

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a -3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

PubMed Central

Carriere, Patrick P.; Llopis, Shawn D.; Naiki, Anna C.; Nguyen, Gina; Phan, Tina; Nguyen, Mary M.; Preyan, Lynez C.; Yearby, Letitia; Pratt, Jamal; Burks, Hope; Davenport, Ian R.; Nguyen, Thu A.; Parker-Lemieux, KiTani; Payton-Stewart, Florastina; Williams, Christopher C.; Boué, Stephen M.; Burow, Matthew E.; Collins-Burow, Bridgette; Hilliard, Aaron; Davidson, A. Michael; Tilghman, Syreeta L.

2015-01-01

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer. PMID:26703648

Job Authority and Breast Cancer

PubMed Central

Pudrovska, Tetyana

2014-01-01

Using the 1957–2011 data from the Wisconsin Longitudinal Study, I integrate the gender relations theory, a life course perspective, and a biosocial stress perspective to explore the effect of women’s job authority in 1975 (at age 36) and 1993 (at age 54) on breast cancer incidence up to 2011. Findings indicate that women with the authority to hire, fire, and influence others’ pay had a significantly higher risk of a breast cancer diagnosis over the next 30 years compared to housewives and employed women with no job authority. Because job authority conferred the highest risk of breast cancer for women who also spent more hours dealing with people at work in 1975, I suggest that the assertion of job authority by women in the 1970s involved stressful interpersonal experiences, such as social isolation and negative social interactions, that may have increased the risk of breast cancer via prolonged dysregulation of the glucocorticoid system and exposure of breast tissue to the adverse effects of chronically elevated cortisol. This study contributes to sociology by emphasizing gendered biosocial pathways through which women’s occupational experiences become embodied and drive forward physiological repercussions. PMID:25506089

Job Authority and Breast Cancer.

PubMed

Pudrovska, Tetyana

2013-01-01

Using the 1957-2011 data from the Wisconsin Longitudinal Study, I integrate the gender relations theory, a life course perspective, and a biosocial stress perspective to explore the effect of women's job authority in 1975 (at age 36) and 1993 (at age 54) on breast cancer incidence up to 2011. Findings indicate that women with the authority to hire, fire, and influence others' pay had a significantly higher risk of a breast cancer diagnosis over the next 30 years compared to housewives and employed women with no job authority. Because job authority conferred the highest risk of breast cancer for women who also spent more hours dealing with people at work in 1975, I suggest that the assertion of job authority by women in the 1970s involved stressful interpersonal experiences, such as social isolation and negative social interactions, that may have increased the risk of breast cancer via prolonged dysregulation of the glucocorticoid system and exposure of breast tissue to the adverse effects of chronically elevated cortisol. This study contributes to sociology by emphasizing gendered biosocial pathways through which women's occupational experiences become embodied and drive forward physiological repercussions.

A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer.

PubMed

Nelson, Michael H; Dolder, Christian R

2007-08-01

Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10-1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated.

[Validation and clinical application of MammaPrint® in patients with breast cancer].

PubMed

Sánchez-Forgach, Ernesto Roberto; Carpinteyro-Espín, Ubaldo; Alemán-Áviles, Jorge Alberto; Sánchez-Basurto, Carlos

In recent years, advances in molecular biology have resulted in innovations in breast cancer diagnostics and therapeutics. The development of genomics has revolutionized our understanding of this disease. MammaPrint ® was developed as a diagnostic tool to predict risk of breast cancer recurrence using the expression of 70 genes altering the clinicopathologic paradigm of selection of patients for adjuvant cytotoxic chemotherapy. A study of stage i-ii breast cancer patients on whom the MammaPrint ® genomic assay was performed. The use of the MammaPrint ® assay was a decisive factor for the recommendation of adjuvant treatment with chemotherapy and/or hormone therapy in patients with high risk for relapse. In our group, the patients with low-risk have not presented local or systemic recurrences DISCUSSION: The determination of the genetic characteristics and its alterations in breast cancer, is fundamentally important for a better identification of risk, as well as a better selection of cancer therapy. MammaPrint ® is an effective study to determine risk of recurrence of in early stage breast cancer. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial.

PubMed

Loibl, Sibylle; Doering, Gabriele; Müller, Lothar; Grote-Metke, Albert; Müller, Roberto; Tomé, Oliver; Wiest, Wolfgang; Maisch, Andrea; Nekljudova, Valentina; von Minckwitz, Gunter

2011-12-01

The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.

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

ClinicalTrials.gov

2017-12-07

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

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. ...

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer.

PubMed

Ramírez-Expósito, María Jesús; Carrera-González, María del Pilar; Mayas, María Dolores; Dueñas, Basilio; Martínez-Ferrol, Julia; Martínez-Martos, José Manuel

2012-05-01

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin-angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers. We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth. Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy.

PubMed

Press, Michael F; Sauter, Guido; Buyse, Marc; Bernstein, Leslie; Guzman, Roberta; Santiago, Angela; Villalobos, Ivonne E; Eiermann, Wolfgang; Pienkowski, Tadeusz; Martin, Miguel; Robert, Nicholas; Crown, John; Bee, Valerie; Taupin, Henry; Flom, Kerry J; Tabah-Fisch, Isabelle; Pauletti, Giovanni; Lindsay, Mary-Ann; Riva, Alessandro; Slamon, Dennis J

2011-03-01

Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. This study was designed to evaluate whether TOP2A gene alterations may predict incremental responsiveness to anthracyclines in some breast cancers. A total of 4,943 breast cancers were analyzed for alterations in TOP2A and HER2. Primary tumor tissues from patients with metastatic breast cancer treated in a trial of chemotherapy plus/minus trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test set followed by evaluation of malignancies from two separate, large trials for changes in these same genes as a validation set. Association between these alterations and clinical outcomes was determined. Test set cases containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC) plus trastuzumab, demonstrated longer progression-free survival compared to those treated with AC alone (P = .0002). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar improvement in survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in a larger validation set, where HER2/TOP2A coamplification was again associated with longer survival when only anthracycline-containing chemotherapy was used for treatment compared with outcome in HER2-positive cancers lacking TOP2A coamplification. In a study involving nearly 5,000 breast malignancies, both test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of an incremental response to anthracycline-based chemotherapy. Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy advantage for breast cancers than previously thought.

A cohort study of permanently reduced work ability in breast cancer patients.

PubMed

Hauglann, Beate; Benth, Jūratė Šaltytė; Fosså, Sophie D; Dahl, Alv A

2012-09-01

The aims of this cohort study were to explore various longitudinal aspects of employment and disability pension due to permanently reduced work ability among women with breast cancer and to investigate the impact of breast cancer on income. In a national register-based controlled cohort study from Norway, 1,548 women diagnosed with breast cancer (all stages) between 1992 and 1996 at the age 45-54 years and 1,548 cancer-free women matched for age, municipality and civil status were followed for up to 14 years. Medical data from the Cancer Registry of Norway were linked with longitudinal data on employment, social security benefits and socio-demography collected from other national official registries. Compared to cancer-free controls, breast cancer patients were significantly more likely to receive disability pension (hazard ratio (HR) 2.7, 95% CI 2.3-3.2) after adjustment for unmatched socio-demographic variables (education, income and children <18 years in the household). Adjusted HR in breast cancer stage I patients was 1.8 (95% CI 1.5-2.3) and 3.0 (95% CI 2.4-3.8) in stage II/III patients compared to controls. The risk increased with mastectomy compared to breast-conserving surgery (HR 1.5, 95% CI 1.2-1.9). At the end of the observation period, employment rates were higher in non-disabled patients than in non-disabled controls (82% vs. 77%, p = 0.008). Working breast cancer patients experienced a temporary negative effect on employment income. A considerable proportion of women with breast cancer will over time experience permanently reduced work ability and become disability pension holders. In case of reduced work ability in breast cancer survivors, medical personel caring for them should consider and discuss with them rehabilitation and workplace adjustment in order to prevent early disability pension.

Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial.

PubMed

Shaashua, Lee; Shabat-Simon, Maytal; Haldar, Rita; Matzner, Pini; Zmora, Oded; Shabtai, Moshe; Sharon, Eran; Allweis, Tanir; Barshack, Iris; Hayman, Lucile; Arevalo, Jesusa; Ma, Jeffrey; Horowitz, Maya; Cole, Steven; Ben-Eliyahu, Shamgar

2017-08-15

Purpose: Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients. Experimental Design: In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers. Results: Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested a priori hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16 - "classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells. Conclusions: Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. Clin Cancer Res; 23(16); 4651-61. ©2017 AACR . ©2017 American Association for Cancer Research.

AURKA F31I Polymorphism and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A CIMBA study

PubMed Central

Couch, Fergus J.; Sinilnikova, Olga; Vierkant, Robert A; Pankratz, V. Shane; Fredericksen, Zachary S.; Stoppa-Lyonnet, Dominique; Coupier, Isabelle; Hughes, David; Hardouin, Agnès; Berthet, Pascaline; Peock, Susan; Cook, Margaret; Baynes, Caroline; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary E.; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Spurdle, Amanda B.; Schmutzler, Rita; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Sutter, Christian; Horst, Jurgen; Schaefer, Dieter; Offit, Kenneth; Kirchhoff, Tomas; Andrulis, Irene L.; Ilyushik, Eduard; Glendon, Gordon; Devilee, Peter; Vreeswijk, Maaike P.G.; Vasen, Hans F.A.; Borg, Ake; Backenhorn, Katja; Struewing, Jeffery P.; Greene, Mark H.; Neuhausen, Susan L.; Rebbeck, Timothy R.; Nathanson, Katherine; Domchek, Susan; Wagner, Theresa; Garber, Judy E.; Szabo, Csilla; Zikan, Michal; Foretova, Lenka; Olson, Janet E.; Sellers, Thomas A.; Lindor, Noralane; Nevanlinna, Heli; Tommiska, Johanna; Aittomaki, Kristiina; Hamann, Ute; Rashid, Muhammad U.; Torres, Diana; Simard, Jacques; Durocher, Francine; Guenard, Frederic; Lynch, Henry T.; Isaacs, Claudine; Weitzel, Jeffrey; Olopade, Olufunmilayo I.; Narod, Steven; Daly, Mary B.; Godwin, Andrew K.; Tomlinson, Gail; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniouon, Antonis C.

2009-01-01

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 co-operate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). CIMBA was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4935 BRCA1 and 2241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations were genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined (HR = 0.91; 95% CI 0.77-1.06). Similarly, no significant association was seen in BRCA1 (HR = 0.90; 95% CI 0.75-1.08) or BRCA2 carriers (HR = 0.93; 95% CI 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. PMID:17627006

Guided Imagery and Relaxation for Women with Early Stage Breast Cancer

ERIC Educational Resources Information Center

Goodwin, Linda K.; Lee, Sang Min; Puig, Ana I.; Sherrard, Peter A. D.

2005-01-01

Fifty-two women with Stage I and Stage II breast cancer agreed to participate in a study to determine the effectiveness of two interventions, guided imagery and relaxation, to enhance psychological well-being. Participants were randomly assigned to either a guided imagery or relaxation group. Forty women completed the study. A student's t-test was…

Mouse mammary tumour virus (MMTV) and human breast cancer with neuroendocrine differentiation.

PubMed

Js, Lawson; Cc, Ngan; Wk, Glenn; Dd, Tran

2017-01-01

Mouse mammary tumour viruses (MMTVs) may have a role in a subset of human breast cancers. MMTV positive human breast cancers have similar histological characteristics to neuroendocrine breast cancers and to MMTV positive mouse mammary tumours. The purpose of this study was to investigate the expression of neuroendocrine biomarkers - synaptophysin and chromogranin, to determine if these histological characteristics and biomarker expression were due to the influences of MMTV. Immunohistochemistry analyses to identify synaptophysin and chromogranin were conducted on a series of human breast cancers in which (i) MMTV had been previously identified and had similar histological characteristics to MMTV positive mouse mammary tumours and (ii) MMTV positive mouse mammary tumours. The expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumors were all positive (7 of 7 specimens - 100% positive). The expression of synaptophysin and chromogranin in MMTV positive human breast cancers was much less prevalent (3 of 22 - 14%). There was no expression of synaptophysin and chromogranin in the normal breast tissue control specimens. It is not possible to draw any firm conclusions from these observations. However, despite the small numbers of MMTV positive mouse mammary tumours in this study, the universal expression in these specimens of synaptophysin and chromogranin proteins is striking. This pattern of synaptophysin and chromogranin expression is very different from their expression in MMTV positive human breast cancers. The reason for these differences is not known. The high prevalence of positive expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumours and low expression of synaptophysin and chromogranin in MMTV positive human breast cancers indicates that MMTV is not usually associated with neuroendocrine human breast cancers.

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques.

PubMed

Koolen, Bas B; Vrancken Peeters, Marie-Jeanne T F D; Aukema, Tjeerd S; Vogel, Wouter V; Oldenburg, Hester S A; van der Hage, Jos A; Hoefnagel, Cornelis A; Stokkel, Marcel P M; Loo, Claudette E; Rodenhuis, Sjoerd; Rutgers, Emiel J Th; Valdés Olmos, Renato A

2012-01-01

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

A systematic review and meta-analysis of the safety, feasibility and effect of exercise in women with stage II+ breast cancer.

PubMed

Singh, Ben; Spence, Rosalind R; Steele, Megan L; Sandler, Carolina X; Peake, Jonathan M; Hayes, Sandra C

2018-05-03

To systematically evaluate the safety, feasibility and effect of exercise among women with stage II+ breast cancer. CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published prior to March 1, 2017. Randomised, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included. Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored. There were no differences in adverse events between exercise and usual care (risk difference: <0.01 [95% CI: -0.01, 0.01]), p=0.38). Median recruitment rate was 56% (1%-96%), withdrawal rate was 10% (0%-41%) and adherence rate was 82% (44%-99%). Safety and feasibility outcomes were similar, irrespective of exercise mode, supervision, duration, or timing. Effects of exercise for quality of life, fitness, fatigue, strength, anxiety, depression, body mass index and waist circumference compared with usual care were significant (standardised mean difference range: 0.17-0.77, p<0.05). The findings support the safety, feasibility and effects of exercise for those with stage II+ breast cancer, suggesting that national and international exercise guidelines appear generalizable to women with local, regional and distant breast cancer. Copyright © 2018. Published by Elsevier Inc.

Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy.

PubMed

Kesler, Shelli R; Watson, Christa; Koovakkattu, Della; Lee, Clement; O'Hara, Ruth; Mahaffey, Misty L; Wefel, Jeffrey S

2013-12-01

Breast cancer survivors are at increased risk for cognitive dysfunction, which reduces quality of life. Neuroimaging studies provide critical insights regarding the mechanisms underlying these cognitive deficits as well as potential biologic targets for interventions. We measured several metabolite concentrations using (1)H magnetic resonance spectroscopy as well as cognitive performance in 19 female breast cancer survivors and 17 age-matched female controls. Women with breast cancer were all treated with chemotherapy. Results indicated significantly increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N-acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared to controls. The breast cancer group reported reduced executive function and memory, and subjective memory ability was correlated with mI and Cho levels in both groups. These findings provide preliminary evidence of an altered metabolic profile that increases our understanding of neurobiologic status post-breast cancer and chemotherapy.

Breast Cancer Overview

MedlinePlus

... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family History of Breast Cancer and Folate Intake.

PubMed

Kim, Hyun Ja; Jung, Seungyoun; Eliassen, A Heather; Chen, Wendy Y; Willett, Walter C; Cho, Eunyoung

2017-09-01

To evaluate the association between alcohol consumption and breast cancer risk in younger women, overall and by family history of breast cancer and folate intake, we prospectively followed 93,835 US women aged 27-44 years in Nurses' Health Study II who had alcohol consumption data in 1991. Alcohol consumption and folate intake were measured by food frequency questionnaire every 4 years. We documented 2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol consumption was not associated with breast cancer risk overall (for intake of ≥10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence interval: 0.94, 1.22). When the association was stratified by family history and folate intake, a positive association between alcohol consumption and breast cancer was found among women with a family history and folate intake less than 400 μg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06, 3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer in other categories of family history and folate intake (P-interaction = 0.55). In conclusion, in this population of younger women, higher alcohol consumption was associated with increased risk of breast cancer among those with both a family history of breast cancer and lower folate intake. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of RPL39 in Metaplastic Breast Cancer.

PubMed

Dave, Bhuvanesh; Gonzalez, Daniel D; Liu, Zhi-Bin; Li, Xiaoxian; Wong, Helen; Granados, Sergio; Ezzedine, Nadeer E; Sieglaff, Douglas H; Ensor, Joe E; Miller, Kathy D; Radovich, Milan; KarinaEtrovic, Agda; Gross, Steven S; Elemento, Olivier; Mills, Gordon B; Gilcrease, Michael Z; Chang, Jenny C

2017-06-01

Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown. The objective of this study was to determine the role and mechanism of action of RPL39 in metaplastic breast cancer. Both competitive allele-specific and droplet digital polymerase chain reaction were used to determine the RPL39 A14V mutation rate in metaplastic breast cancer patient samples. The impact of RPL39 and iNOS expression on patient overall survival was estimated using the Kaplan-Meier method. Co-immunoprecipitation and immunoblot analyses were used for mechanistic evaluation of RPL39. The RPL39 A14V mutation rate was 97.5% (39/40 tumor samples). High RPL39 (hazard ratio = 0.71, 95% confidence interval = 0.55 to 0.91, P = 006) and iNOS expression (P = 003) were associated with reduced patient overall survival. iNOS inhibition with the pan-NOS inhibitor N G -methyl-L-arginine acetate decreased in vitro proliferation and migration, in vivo tumor growth in both BCM-4664 and BCM-3807 patient-derived xenograft models (P = 04 and P = 02, respectively), and in vitro and in vivo chemoresistance. Mechanistically, RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. NOS inhibitors and RNA editing modulators may offer novel treatment options for metaplastic breast cancer. © The Author 2016. Published by Oxford University Press.

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis.

PubMed

Zhong, Jing-Min; Li, Jing; Kang, An-Ding; Huang, San-Qian; Liu, Wen-Bin; Zhang, Yun; Liu, Zhi-Hong; Zeng, Liang

2018-04-01

Breast cancer is the most common malignancy in females, with metastasis of this type of cancer frequently proving lethal. However, there are still no effective biomarkers to predict breast cancer metastasis. The aim of the present study was, therefore, to analyze breast cancer metastasis-associated proteins and evaluate the association between protein S100-A8 and the prognosis of breast cancer. The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technique was used to analyze the differential expression of proteins between fresh primary breast tumor (PBT) tissue and fresh paired metastatic lymph nodes (PMLN) tissue. Subsequently, immunohistochemical staining was used to locate and assess the expression of protein S100-A8 in benign breast disease (n=15), primary breast cancer with (n=109) or without (n=83) metastasis, and in paired metastatic lymph nodes (n=109) formalin fixed paraffin embedded (FFPE) tissue. Staining scores were evaluated and the association between protein S100-A8 expression levels and the clinicopathological characteristics of 192 patients with breast cancer were evaluated using the χ 2 test. Kaplan-Meier and Cox hazards regression analyses were utilized to investigate the association between the expression of protein S100-A8 and the prognosis of patients with breast cancer. A total of 4,837 proteins were identified using the iTRAQ proteomic technique. Among these proteins, 643 differentially expressed proteins were revealed. Protein S100-A8 expression levels were identified to differ between PBT and PMLN tissues. Immunohistochemical staining suggested a significant difference between NMBT and PMLN (P=0.002), and also between PBT and PMLN (P<0.001). Cox hazards regression model analyses suggested that histological grade (P=0.031) and nodal status (P=0.001) were risk factors for lymph nodes metastasis of breast cancer. Kaplan-Meier analyses revealed no significant relationship between protein S100-A8 expression level and

Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses' Health Study II

PubMed Central

2011-01-01

Introduction Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent. Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D (25(OH)D) are considered the best measure of vitamin D status. Methods We conducted a prospective nested case-control study within the Nurses' Health Study II (NHSII). Plasma samples collected in 1996 to 1999 were assayed for 25(OH)D in 613 cases, diagnosed after blood collection and before 1 June 2007, and in 1,218 matched controls. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for several breast cancer risk factors. Results No significant association was observed between plasma 25(OH)D levels and breast cancer risk (top vs. bottom quartile multivariate RR = 1.20, 95% CI (0.88 to 1.63), P-value, test for trend = 0.32). Results were similar when season-specific quartile cut points were used. Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis. Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors (P-value, test for heterogeneity = 0.51). The association did not vary by age at blood collection or season of blood collection, but did vary when stratified by body mass index (P-value, test for heterogeneity = 0.01). Conclusions Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population. PMID:21569367

[Utility of chromosome banding with ALU I enzyme for identifying methylated areas in breast cancer].

PubMed

Rojas-Atencio, Alicia; Yamarte, Leonard; Urdaneta, Karelis; Soto-Alvarez, Marisol; Alvarez Nava, Francisco; Cañizalez, Jenny; Quintero, Maribel; Atencio, Raquel; González, Richard

2012-12-01

Cancer is a group of disorders characterized by uncontrolled cell growth which is produced by two successive events: increased cell proliferation (tumor or neoplasia) and the invasive capacity of these cells (metastasis). DNA methylation is an epigenetic process which has been involved as an important pathogenic factor of cancer. DNA methylation participates in the regulation of gene expression, directly, by preventing the union of transcription factors, and indirectly, by promoting the "closed" structure of the chromatine. The objectives of this study were to identify hypermethyled chromosomal regions through the use of restriction Alu I endonuclease, and to relate cytogenetically these regions with tumor suppressive gene loci. Sixty peripheral blood samples of females with breast cancer were analyzed. Cell cultures were performed and cytogenetic spreads, previously digested with Alu I enzyme, were stained with Giemsa. Chromosomal centromeric and not centromeric regions were stained in 37% of cases. About 96% of stained hypermethyled chromosomal regions (1q, 2q, 6q) were linked with methylated genes associated with breast cancer. In addition, centromeric regions in chromosomes 3, 4, 8, 13, 14, 15 and 17, usually unstained, were found positive to digestion with Alu I enzime and Giemsa staining. We suggest the importance of this technique for the global visualization of the genome which can find methylated genes related to breast cancer, and thus lead to a specific therapy, and therefore a better therapeutic response.

Importance of adherence to guidelines in breast cancer clinical practice. The Italian experience (AIOM).

PubMed

Barni, Sandro; Venturini, Marco; Molino, Annamaria; Donadio, Michela; Rizzoli, Sara; Maiello, Evaristo; Gori, Stefania

2011-01-01

Project RIGHT (Research for the Identification of the most effective and hIGHly accepted clinical guidelines for cancer Treatment) is promoted by the Italian Association of Medical Oncology (AIOM) to evaluate the concordance between AIOM breast cancer guidelines and clinical practice in Italy. In RIGHT-1, feasibility and the appropriateness of indicators were assessed in patients with early breast cancer. RIGHT-2 evaluated the compliance with guidelines in a nationwide program. Thirty-five Italian centers participated in the RIGHT-2 survey. Ten indicators were evaluated to verify an agreement between 2005 AIOM breast cancer guidelines and practice. Patients with clinical stage I-II invasive breast cancer, age ≤70 years, who had their first visit at the oncology center between October 2005 and November 2006 were included. In RIGHT-2, ≥90% adherence for the diagnosis indicator and three therapy indicators were observed. The lowest degree of compliance (0%) was observed for the follow-up indicator in asymptomatic patients. In RIGHT-2, compliance to the 2005 AIOM breast cancer guidelines was 64%. When the follow-up indicator was eliminated, overall adherence to AIOM guidelines was 71%. The results highlight the need to continue improving the already good standards of breast cancer care.

Breast Cancer -- Male

MedlinePlus

... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

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

ClinicalTrials.gov

2018-02-12

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

Breast Cancer Surgery

MedlinePlus

FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

Clinical audit system as a quality improvement tool in the management of breast cancer.

PubMed

Vijayakumar, Chellappa; Maroju, Nanda Kishore; Srinivasan, Krishnamachari; Reddy, K Satyanarayana

2016-11-01

Quality improvement is recognized as a major factor that can transform healthcare management. This study is a clinical audit that aims at analysing treatment time as a quality indicator and explores the role of setting a target treatment time on reducing treatment delays. All newly diagnosed patients with breast cancer between September 2011 and August 2013 were included in the study. Clinical care pathway for breast cancer patients was standardized and the timeliness of care at each step of the pathway was calculated. Data collection was spread over three phases, baseline, audit cycle I, and audit cycle II. Each cycle was preceded by a quality improvement intervention, and followed by analysis. A total of 334 patients with breast cancer were included in the audit. The overall time from first visit to initiation of treatment was 66.3 days during the baseline period. This improved to 40.4 and 28.5 days at the end of Audit cycle I and II, respectively. The idealized target time of 28 days for initiating treatment was achieved in 5, 23.5, and 65.2% of patients in the baseline period, Audit cycle I, and Audit Cycle II, respectively. There was improvement noted across all steps of the clinical care pathway. This study confirms that audit is a powerful tool in quality improvement programs and helps achieve timely care. Gains achieved through an audit process may not be sustainable unless underlying patient factors and resource deficits are addressed. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy

PubMed Central

Watson, Christa; Koovakkattu, Della; Lee, Clement; O’Hara, Ruth; Mahaffey, Misty L.; Wefel, Jeffrey S.

2013-01-01

Breast cancer survivors are at increased risk for cognitive dysfunction, which reduces quality of life. Neuroimaging studies provide critical insights regarding the mechanisms underlying these cognitive deficits as well as potential biologic targets for interventions. We measured several metabolite concentrations using 1H magnetic resonance spectroscopy as well as cognitive performance in 19 female breast cancer survivors and 17 age-matched female controls. Women with breast cancer were all treated with chemotherapy. Results indicated significantly increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N-acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared to controls. The breast cancer group reported reduced executive function and memory, and subjective memory ability was correlated with mI and Cho levels in both groups. These findings provide preliminary evidence of an altered metabolic profile that increases our understanding of neurobiologic status post-breast cancer and chemotherapy. PMID:23536015

Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients

PubMed Central

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Żaczek, Anna J.

2013-01-01

Introduction Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Materials and Methods Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). Results ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. Conclusions ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype. PMID:23951298

Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 polymorphisms in breast cancer patients.

PubMed

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Zaczek, Anna J

2013-01-01

Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

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

ClinicalTrials.gov

2017-12-18

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

6 Common Cancers - Breast Cancer

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

Engagement of I-Branching β-1, 6-N-Acetylglucosaminyltransferase 2 in Breast Cancer Metastasis and TGF-β Signaling

PubMed Central

Zhang, Haijun; Meng, Fanyan; Wu, Sherwin; Kreike, Bas; Sethi, Seema; Chen, Wei; Miller, Fred R.; Wu, Guojun

2014-01-01

In this study, we have showed that GCNT2, a gene-encoding glucosaminyl (N-acetyl) transferase 2, I-branching enzyme, is overexpressed in highly metastatic breast cancer cell lines of human and mouse origin and basal-like breast tumor samples. GCNT2 expression is also significantly correlated to the metastatic phenotype in breast tumor samples. Functional studies showed that ectopic expression of GCNT2 enhances cell detachment, adhesion to endothelial cells, cell migration and invasion in vitro, and lung metastasis of breast cancer cells in vivo. Knockdown of GCNT2 expression decreases cell migration and invasion in vitro and lung metastasis in vivo. We have further shown the involvement of GCNT2 in the epithelial-to-mesenchymal transition (EMT). Specifically, the expression of E-cadherin is significantly changed upon GCNT2 expression at the protein level but not at the RNA level. Moreover, we have shown that GCNT2 is a direct target of the TGF-β–smad pathway and that change in GCNT2 expression modulates EMT induced by TGF-β1 treatment. Finally, we have shown that diminution of the glycosyltransferase activity of I-branching β-1, 6-N-acetylglucosaminyl transferase 2 (GCNT2) abrogates its cell migration and invasion-promoting function and synergistic effect with TGF-β to induce EMT. Our study for the first time showed that GCNT2 is a novel gene contributing to breast cancer metastasis with preferential expression in basal-like breast cancer. Moreover, we discovered that involvement of GCNT2 in EMT and TGF-β signaling, and further glycosylation modification of E-cadherin by GCNT2, are the underlying integrative mechanisms for breast cancer metastasis, implying that blocking TGF-β/GCNT2 signaling is a promising approach for targeting metastatic breast cancer. PMID:21750175

TEN-YEAR RECURRENCE RATES IN YOUNG WOMEN WITH BREAST CANCER BY LOCOREGIONAL TREATMENT APPROACH

PubMed Central

Beadle, Beth M.; Woodward, Wendy A.; Tucker, Susan L.; Outlaw, Elesyia D.; Allen, Pamela K.; Oh, Julia L.; Strom, Eric A.; Perkins, George H.; Tereffe, Welela; Yu, Tse-Kuan; Meric-Bernstam, Funda; Litton, Jennifer K.; Buchholz, Thomas A.

2011-01-01

Purpose Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Methods and Materials Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Conclusions Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach. PMID:18707822

Effect of {sup 18}F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

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

Groheux, David; Moretti, Jean-Luc; EAD Imagerie Moleculaire Diagnostique et Ciblage Therapeutique, IUH, University of Paris VII, Paris

2008-07-01

Purpose: To investigate the potential effect of using {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. Methods and Materials: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. Results: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in themore » subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. Conclusions: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.« less

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

ClinicalTrials.gov

2017-07-10

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

A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer

PubMed Central

Nelson, Michael H; Dolder, Christian R

2007-01-01

Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10–1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated. PMID:18472989

Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer.

PubMed

Lawson, James S; Glenn, Wendy K

2017-01-01

Multiple oncogenic viruses including, mouse mammary tumor virus, bovine leukemia virus, human papilloma virus, and Epstein Barr virus, have been identified as separate infectious pathogens in human breast cancer. Here we demonstrate that these four viruses may be present in normal and benign breast tissues 1 to 11 years before the development of same virus breast cancer in the same patients. We combined the data we developed during investigations of the individual four oncogenic viruses and breast cancer. Patients who had benign breast biopsies 1-11 years prior to developing breast cancer were identified by pathology reports from a large Australian pathology service (Douglas Hanly Moir Pathology). Archival formalin fixed specimens from these patients were collected. The same archival specimens were used for (i) investigations of mouse mammary tumour virus (also known as human mammary tumour virus) conducted at the Icahn School of Medicine at Mount Sinai, New York and at the University of Pisa, Italy, (ii) bovine leukemia virus conducted at the University of California at Berkeley,(iii) human papilloma virus and Epstein Barr virus conducted at the University of New South Wales, Sydney, Australia. Seventeen normal breast tissues from cosmetic breast surgery conducted on Australian patients were used as controls. These patients were younger than those with benign and later breast cancer. Standard and in situ polymerase chain reaction (PCR) methods were used to identify the four viruses. The detailed methods are outlined in the separate publications.: mouse mammary tumor virus, human papilloma virus and Epstein Barr virus (Infect Agent Cancer 12:1, 2017, PLoS One 12:e0179367, 2017, Front Oncol 5:277, 2015, PLoS One 7:e48788, 2012). Epstein Barr virus and human papilloma virus were identified in the same breast cancer cells by in situ PCR. Mouse mammary tumour virus was identified in 6 (24%) of 25 benign breast specimens and in 9 (36%) of 25 breast cancer specimens

[Update of breast cancer in primary care (I/V)].

PubMed

Vich, P; Brusint, B; Alvarez-Hernández, C; Cuadrado-Rouco, C; Diaz-García, N; Redondo-Margüello, E

2014-09-01

Breast cancer is a prevalent disease affecting all areas of the patients' lives. Therefore, family physicians should have a thorough knowledge of this disease in order to optimize the health care services for these patients, and making the best use of available resources. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. The first article reviews the epidemiology, risk factors, and protective factors in this disease This summary report aims to provide a current and practical review on breast cancer, providing answers to family doctors and helping them to support the patients for their benefit throughout their illness. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

ClinicalTrials.gov

2018-04-23

Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme; Triple Negative Breast Cancer

MEK Inhibition Leads To Lysosome-Mediated Na+/I- Symporter Protein Degradation In Human Breast Cancer Cells

PubMed Central

Zhang, Zhaoxia; Beyer, Sasha; Jhiang, Sissy M

2013-01-01

The Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates active iodide uptake into thyroid follicular cells. NIS-mediated iodide uptake in thyroid cells is the basis for targeted radionuclide imaging and treatment of differentiated thyroid carcinomas and their metastases. Furthermore, NIS is expressed in many human breast tumors but not in normal non-lactating breast tissue, suggesting that NIS-mediated radionuclide uptake may also allow the imaging and targeted therapy of breast cancer. However, functional cell surface NIS expression is often low in breast cancer, making it important to uncover signaling pathways that modulate NIS expression at multiple levels, from gene transcription to post-translational processing and cell surface trafficking. In this study, we investigated NIS regulation in breast cancer by MEK (MAPK/ERK kinase) signaling, an important cell signaling pathway involved in oncogenic transformation. We found that MEK inhibition decreased NIS protein levels in all-trans retinoic acid (tRA)/hydrocortisone treated MCF-7 cells as well as human breast cancer cells expressing exogenous NIS. The decrease in NIS protein levels by MEK inhibition was not accompanied by a decrease in NIS mRNA or a decrease in NIS mRNA export from the nucleus to the cytoplasm. NIS protein degradation upon MEK inhibition was prevented by lysosome inhibitors, but not by proteasome inhibitors. Interestingly, NIS protein level was correlated with MEK/ERK activation in human breast tumors from a tissue microarray. Taken together, MEK activation appears to play an important role in maintaining NIS protein stability in human breast cancers. PMID:23404856

Hand-Ground Nanoscale ZnII -Based Coordination Polymers Derived from NSAIDs: Cell Migration Inhibition of Human Breast Cancer Cells.

PubMed

Paul, Mithun; Sarkar, Koushik; Deb, Jolly; Dastidar, Parthasarathi

2017-04-27

Increased levels of intracellular prostaglandin E 2 (PGE 2 ) have been linked with the unregulated cancer cell migration that often leads to metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) are known inhibitors of cyclooxygenase (COX) enzymes, which are responsible for the increased PGE 2 concentration in inflamed as well as cancer cells. Here, we demonstrate that NSAID-derived Zn II -based coordination polymers are able to inhibit cell migration of human breast cancer cells. Various NSAIDs were anchored to a series of 1D Zn II coordination polymers through carboxylate-Zn coordination, and these structures were fully characterized by single-crystal X-ray diffraction. Hand grinding in a pestle and mortar resulted in the first reported example of nanoscale coordination polymers that were suitable for biological studies. Two such hand-ground nanoscale coordination polymers NCP1 a and NCP2 a, which contained naproxen (a well-studied NSAID), were successfully internalized by the human breast cancer cells MDA-MB-231, as was evident from cellular imaging by using a fluorescence microscope. They were able to kill the cancer cells (MTT assay) more efficiently than the corresponding mother drug naproxen, and most importantly, they significantly inhibited cancer cell migration thereby displaying anticancer activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

PubMed

Pouw, Bas; de Wit-van der Veen, Linda J; van Duijnhoven, Frederieke; Rutgers, Emiel J Th; Stokkel, Marcel P M; Valdés Olmos, Renato A; Vrancken Peeters, Marie-Jeanne T F D

2016-05-01

Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery. Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds. Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous. Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

PubMed

Martinez, Jessica A; Chalasani, Pavani; Thomson, Cynthia A; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A; Villa-Guillen, Diana Evelyn; Chow, H-H Sherry

2016-07-19

Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin

Epigenetic suppression of neprilysin regulates breast cancer invasion.

PubMed

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-03-07

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

Epigenetic suppression of neprilysin regulates breast cancer invasion

PubMed Central

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-01-01

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

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

Tiang, Jacky M.; Butcher, Neville J., E-mail: n.butcher@uq.edu.au; Minchin, Rodney F.

2010-02-26

Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phasemore » of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.« less

Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-28

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

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

PubMed

Poudrier, Jennifer; Mac-Lean, Roanne Thomas

2009-12-01

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

Breast cancer in young women in a limited-resource environment.

PubMed

Basro, Sarinah; Apffelstaedt, Justus P

2010-07-01

Despite the higher incidence of breast cancer in young women in developing countries, there is a paucity of data on their management. We present the clinicopathological features and outcome of treatment of women 35 years or younger with breast cancer in a resource-restricted environment. A total of 141 patients who were diagnosed with primary breast cancer at 35 years or younger from January 2000 to June 2008 were retrieved from the cancer registry of a breast clinic at a tertiary hospital and a private breast health center in South Africa. Clinicopathological features, treatment, and survival were analyzed. Two patients presented with TNM stage 0 (1.4%), 14 with stage I (9.9%), 47 with stage II (33.35%), 47 with stage III (33.3%), and 31 with stage IV (21.9%). Tumor grade was 3 in 47%, grade 2 in 37%, and grade 1 in 16% of patients. One hundred and four patients with stage 0-III disease underwent treatment with curative intent, 83 had a mastectomy, and 12 had breast-conserving surgery. Ninety patients (86.5%) had chemotherapy, 68 (65.4%) had radiotherapy, and 50 (48.1%) had hormonal therapy. Of 93 patients who completed primary therapy, 4 developed contralateral cancers, 3 had locoregional recurrence, 8 developed synchronous locoregional and distant recurrence, and 19 relapsed with distant metastasis only. The 2-year disease-free and overall survival for stage 0-III disease was 48 and 56%, respectively. Young women with breast cancer in a resource-limited environment have similar adverse clinicopathological features to those in developed countries. Their disease is more advanced at presentation with poorer outcome. Increased awareness, better systemic therapy, and more comprehensive genetic studies are essential to improve the dismal outcome.

Breast cancer diagnosis: Imaging techniques and biochemical markers.

PubMed

Jafari, Seyed Hamed; Saadatpour, Zahra; Salmaninejad, Arash; Momeni, Fatemeh; Mokhtari, Mojgan; Nahand, Javid Sadri; Rahmati, Majid; Mirzaei, Hamed; Kianmehr, Mojtaba

2018-07-01

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer. © 2017 Wiley Periodicals, Inc.

Breast Cancer

MedlinePlus

Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

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

Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.

PubMed

Kaaks, Rudolf; Johnson, Theron; Tikk, Kaja; Sookthai, Disorn; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Dossus, Laure; Rinaldi, Sabina; Romieu, Isabelle; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Buckland, Genevieve; Argüelles, Marcial; Sánchez, María-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H Bas; van Gils, Carla H; Peeters, Petra H; Andersson, Anne; Sund, Malin; Weiderpass, Elisabete; Gram, Inger Torhild; Lund, Eiliv; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Travis, Ruth C; Merritt, Melissa A; Gunter, Marc J; Riboli, Elio; Lukanova, Annekatrin

2014-06-01

Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01-1.89]; OR = 1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older. © 2013 UICC.

Risk of developing invasive breast cancer in Hispanic women: A look across Hispanic subgroups

PubMed Central

Banegas, Matthew P.; Leng, Mei; Graubard, Barry I.; Morales, Leo S.

2012-01-01

Background Current evidence on breast cancer among US Hispanic women indicates a significant public health threat, although few studies assess the heterogeneity in breast cancer risk among Hispanics of different origin. Methods The 2000 and 2005 National Health Interview Survey (NHIS) Cancer Control Modules were used to examine the Breast Cancer Risk Assessment Tool (BCRAT) 5-year and lifetime risk of invasive breast cancer among Mexican/Mexican-American, Puerto Rican, Cuban/Cuban-American, Dominican (Republic), Central/South American, Other Hispanic and non-Hispanic white (NHW) women aged 35-84 years. Multiple linear regression models were used to compare the BCRAT 5-year and lifetime breast cancer risk between: i) Hispanics and NHWs and ii) Hispanic subgroups. Results Hispanics had significantly lower mean BCRAT 5-year and lifetime breast cancer risk compared to NHWs (p<0.001). Among Hispanic subgroups, Cuban/Cuban-Americans had a higher BCRAT 5-year risk (p<0.05), while Dominicans had a higher lifetime risk (p<0.001), compared to Mexican/Mexican-American women. Approximately, 2.6% of Hispanic women were at high-risk for breast cancer (BCRAT 5-year risk ≥1.67%), ranging from 1.0% of Central/South Americans to 3.7% of Puerto Ricans; few Hispanics (0.2%) had a lifetime risk ≥20.0%. Conclusions Our findings indicate that Hispanics had significantly lower risk of breast cancer, compared to NHWs, though BCRAT risk significantly differed between specific Hispanic subgroups. We provide estimates of the number of US Hispanic women, from six subgroups, who would be eligible for prophylactic breast cancer chemoprevention. Future studies should further investigate the heterogeneity in breast cancer risk and risk factors between Hispanic women of different origins. PMID:23224859

Healthcare utilization, Medicare spending, and sources of patient distress identified during implementation of a lay navigation program for older patients with breast cancer.

PubMed

Rocque, Gabrielle B; Williams, Courtney P; Jones, Meredith I; Kenzik, Kelly M; Williams, Grant R; Azuero, Andres; Jackson, Bradford E; Halilova, Karina I; Meneses, Karen; Taylor, Richard A; Partridge, Ed; Pisu, Maria; Kvale, Elizabeth A

2018-01-01

Despite benefits for patients, sustainability of breast cancer navigation programs is challenging due to the lack of reimbursement for navigators. This analysis describes distress reported by breast cancer patients to navigators and the impact of navigation on healthcare utilization for older adults with breast cancer. We conducted a retrospective cohort study of Medicare administrative claims data and patient-reported distress assessments. The primary outcome was Medicare spending per beneficiary per quarter. Secondary outcomes included (1) the number of hospitalizations or ER visits in each quarter; (2) distress levels; and (3) causes of distress reported by patients to their navigators. A subset analysis was conducted for stage I/II/III versus stage IV patients. 776 navigated and 776 control patients were included in the analysis. The average age at diagnosis was 74 years; 13% of the subjects were African American; 95% of patients had stage I-III. Medicare spending declined faster for the navigated group than the matched comparison group by $528 per quarter per patient (95% CL -$667, -$388). Stage I/II/III navigated patients showed a statistically significant decline in Medicare spending, ER visits, and hospitalizations over time compared to the matched comparison group. No differences were observed for stage IV patients. Eighteen percent of patients reported moderate distress. Informational and physical distress were more common in late stage than in early-stage breast cancer. Lay navigation reduced healthcare utilization in older adults with breast cancer, with the greatest impact observed in early-stage breast cancer patients.

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.

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

ClinicalTrials.gov

2018-06-18

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

Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype

PubMed Central

Sun, Xuezheng; Nichols, Hazel B.; Tse, Chiu-Kit; Bell, Mary B.; Robinson, Whitney R.; Sherman, Mark E.; Olshan, Andrew F.; Troester, Melissa A.

2015-01-01

Background Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis has received limited attention. Methods Study participants were 1,140 invasive breast cancer patients from Phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer (BC)-specific and overall survival was assessed using Cox proportional hazards models. Results During follow-up (median =13.5 years), 450 patients died, 61% due to breast cancer (n=276). High parity (3+ births) and recent birth (< 5 years before diagnosis) were positively associated with BC-specific mortality, independent of age, race, and selected socioeconomic factors (parity, reference=nulliparous, adjusted hazard ratio [HR]=1.76, 95% confidence interval [CI]=1.13-2.73; birth recency, reference=10+ years, adjusted HR=1.29, 95% CI=0.79, 2.11). The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. Conclusions Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long-term survivors. Impact The biological effects of parity and birth recency may extend from etiology to tumor promotion and progression. PMID:26545404

Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

PubMed

Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

2012-01-01

The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

The breast cancer fanfare: Sociocultural factors and women's health in Ghana.

PubMed

Tetteh, Dinah A

2017-04-01

Traditional notions of the "full" woman and sociocultural beliefs about gender roles contribute to a unique experience of breast cancer in Africa. I used the critical feminist lens to analyze dis-courses about breast cancer in mainstream Ghanaian media. I found that breast cancer awareness is promoted amidst fanfare and that cultural notions of the female breasts, including their sexual appeal, are implied in breast cancer discourse. This obscures a nuanced understanding of the disease and women's health globally, limits the power of women to name their experiences, and contributes to the late presentation of the dis-ease in sub-Saharan Africa. I discuss the implications of the findings for international, interdisciplinary scholarship.

Exploration of how women make treatment decisions after a breast cancer diagnosis.

PubMed

Spittler, Cheryl A; Pallikathayil, Leonie; Bott, Marjorie

2012-09-01

To examine the information needs of women after receiving a diagnosis of breast cancer, investigate how decisions about treatment options are made, and assess personal responses to the decisions made. Mixed-methods approach using quantitative and qualitative data. The University of Kansas Medical Center and Quinn Plastic Surgery Center, both in the midwestern United States. 102 breast cancer survivors who had completed all forms of treatment for at least three months and less than five years. Phase I participants completed five questionnaires about informational needs, confidence and satisfaction with the decision, decisional regret, and conflict. In phase II, 15 participants were purposively sampled from the 102 survivors to participate in a focus group session. Data analysis included frequencies and multiple regression for phase I and qualitative content analysis for phase II. Informational needs, confidence and satisfaction with the decision, and decisional regret and conflict. The variables (widowed, confidence and satisfaction with decision, and decisional conflict and regret) significantly (p = 0.01) accounted for 14% of the variance in informational needs. Two themes emerged from the study: (a) feelings, thoughts, and essential factors that impact treatment considerations, and (b) tips for enhancing treatment consideration options. The study's results show that women viewed informational needs as very important in making treatment decisions after being diagnosed with breast cancer. The treatment team should provide the information, with consideration of the patient's personal preferences, that will assist women to make informed, confident, and satisfied decisions about treatment choices.

Novel modeling of cancer cell signaling pathways enables systematic drug repositioning for distinct breast cancer metastases.

PubMed

Zhao, Hong; Jin, Guangxu; Cui, Kemi; Ren, Ding; Liu, Timothy; Chen, Peikai; Wong, Solomon; Li, Fuhai; Fan, Yubo; Rodriguez, Angel; Chang, Jenny; Wong, Stephen T C

2013-10-15

A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal number of enriched signaling pathways specific to a given metastasis, and (ii) CSB proteins are involved in the most differential expressed coding genes specific to each breast cancer metastasis. The identified signaling networks for the three types of breast cancer metastases contain 31, 15, and 18 proteins and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases. We conducted both in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Of special note, we found that the Food and Drug Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases derived from breast cancer, addressing one particularly challenging aspect of this disease. ©2013 AACR.

and Sporadic Breast Cancer Patients in Rwanda

PubMed

Habyarimana, Thierry; Attaleb, Mohammed; Mugenzi, Pacifique; Mazarati, Jean Baptiste; Bakri, Youssef; El Mzibri, Mohammed

2018-02-26

Worldwide, breast cancer is the most frequent neoplasm and the second leading cause of cancer death among females. It dominates in both developed and developing countries and represents a major public health problem. The etiology is multifactorial and involves exogenous agents as well as endogenous factors. Although they account for only a small fraction of the breast cancer burden, mutations in the BRCA1 and BRCA2 genes are known to confer a high risk predisposition. Mutations in moderate/low-penetrance genes may also contribute to breast cancer risk. Previous studies have shown that mutations in the CHEK2 gene are involved in breast cancer susceptibility due to its impact on DNA repair processes and replication checkpoints. This study was conducted to evaluate the frequencies of three germline mutations in CHEK2 gene (c.1100delC, R145W and I157T) in breast cancers in Rwanda. Using direct DNA sequencing, we analyzed 41 breast cancer patients and 42 normal breast controls but could not detect any positives. CHEK2 mutations may be a rare event in Rwandan population and may only play a minor if an role in breast cancer predisposition among familial and sporadic cases. Creative Commons Attribution License

MMP9 polymorphisms and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

PubMed

Beeghly-Fadiel, Alicia; Lu, Wei; Shu, Xiao-Ou; Long, Jirong; Cai, Qiuyin; Xiang, Yongbin; Gao, Yu-Tang; Zheng, Wei

2011-04-01

In addition to tumor invasion and angiogenesis, matrix metalloproteinase (MMP)9 also contributes to carcinogenesis and tumor growth. Genetic variation that may influence MMP9 expression was evaluated among participants of the Shanghai Breast Cancer Genetics Study (SBCGS) for associations with breast cancer susceptibility. In stage 1, 11 MMP9 single nucleotide polymorphisms (SNPs) were genotyped by the Affymetrix Targeted Genotyping System and/or the Affymetrix Genome-Wide Human SNP Array 6.0 among 4,227 SBCGS participants. One SNP was further genotyped using the Sequenom iPLEX MassARRAY platform among an additional 6,270 SBCGS participants. Associations with breast cancer risk were evaluated by odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models that included adjustment for age, education, and genotyping stage when appropriate. In Stage 1, rare allele homozygotes for a promoter SNP (rs3918241) or a non-synonymous SNP (rs2274756, R668Q) tended to occur more frequently among breast cancer cases (P value = 0.116 and 0.056, respectively). Given their high linkage disequilibrium (D' = 1.0, r (2) = 0.97), one (rs3918241) was selected for additional analysis. An association with breast cancer risk was not supported by additional Stage 2 genotyping. In combined analysis, no elevated risk of breast cancer among homozygotes was found (OR: 1.2, 95% CI: 0.8-1.8). Common genetic variation in MMP9 was not found to be significantly associated with breast cancer susceptibility among participants of the Shanghai Breast Cancer Genetics Study.

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

PubMed

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-07-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

NASA Astrophysics Data System (ADS)

Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

1998-05-01

Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?

PubMed

McGee, Jacob; Giannakeas, Vasily; Karlan, Beth; Lubinski, Jan; Gronwald, Jacek; Rosen, Barry; McLaughlin, John; Risch, Harvey; Sun, Ping; Foulkes, William D; Neuhausen, Susan L; Kotsopoulos, Joanne; Narod, Steven A

2017-05-01

Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening. First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality. Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer. Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer. Copyright © 2017

Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

ClinicalTrials.gov

2017-09-25

Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

Lifestyle changes during adolescence and risk of breast cancer: an ecologic study of the effect of World War II in Norway.

PubMed

Tretli, S; Gaard, M

1996-09-01

There are biologic reasons to believe that the period between the larche and the first full-term pregnancy is a particularly sensitive period in a woman's life regarding the development of breast cancer. In this ecologic study, data provided by the Norwegian Cancer Registry were analyzed to compare risk of breast cancer among women who experienced this sensitive period before, during, or after World War II. An ordinary age-cohort model and a model where the cohort was described by exposure by calendar period and sensitivity to this exposure at different ages, were fitted to the data. The incidence of breast cancer was lower than expected among women who experienced puberty during the war. The estimated configuration of the exposure variable showed an increase in exposure up to the start of WWII to twice the level in 1916, dropped by 13 percent during the war, and increased again after the war. The level in 1975 was approximately 2.7 times higher than the level in 1916. The results indicate that one or more lifestyle factors that changed among adolescent women during the war, influenced their risk of breast cancer. Dietary intake of energy, fat, meat, milk, fish, fresh vegetables, and potatoes, in addition to physical activity level and height, are important factors to consider in relation to breast cancer risk.

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

PubMed

O'Scanaill, P; Keane, S; Wall, V; Flood, G; Buggy, D J

2018-04-01

Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h -1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. AUC moving was mean (SD) 71 (34) mm h -1 vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. NCT 03024697. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

PubMed

Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J

2016-07-07

The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete

Phase I trial of the androgen receptor modulator CR1447 in breast cancer patients.

PubMed

Zweifel, Martin; Thürlimann, Beat; Riniker, Salome; Weder, Patrik; von Moos, Roger; Pagani, Olivia; Bigler, Martin; Rothgiesser, Karin M; Pilop, Christiane; Hawle, Hanne; Brauchli, Peter; Tapia, Coya; Schoenfeld, Wolfgang; Sessa, Cristiana

2017-10-01

CR1447 (4-hydroxytestosterone, 4-OHT) binds to the androgen receptor and has antiproliferative activity in both ER-positive and ER-negative/AR-positive breast cancer cells in preclinical studies. The objective of this first-in man trial was to evaluate the safety and to determine the dose of CR1447, administered as an ointment, for Phase II. Escalating doses (100, 200, 400 mg) of CR1447 were administered topically on a daily basis to patients with ER-positive/AR-positive/HER2-negative advanced breast cancer pretreated with several lines of therapy. 14 patients have been treated for a total of 42 cycles. Two patients, one at dose level 100 mg and one at dose level 200 mg, showed early tumour progression and were replaced. Related adverse events were all ≤ grade 2 and included fatigue, bone and joint pain, stiffness, dry skin and mouth, nausea, sweating, urinary tract infection, rash, headache and distress. No drug-related dose-limiting toxicities (DLTs) were seen. Two patients (17%) achieved stable disease at 3 months. Pharmacokinetic analysis confirmed dose-dependent transdermal uptake of CR1447. 4-OH-androstenedione (4-OHA), a key metabolite of 4-OHT, was undetectable in most of the plasma samples. Urine metabolites of 4-OHT and 4-OHA indicate high exposure of 4-OHT after topical administration. Oestradiol serum concentrations did not increase, confirming preclinical data that CR1447 is not converted to estrogens in vivo In conclusion, CR1447 administered transdermally as an ointment is well tolerated and appears to have single-agent activity in heavily pretreated ER-positive/HER2-negative breast cancer patients. The recommended phase II dose is 400 mg/day. © 2017 The authors.

Common breast cancer susceptibility loci are associated with triple negative breast cancer

PubMed Central

Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

2012-01-01

Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

Bioavailable insulin-like growth factor-I as mediator of racial disparity in obesity-relevant breast and colorectal cancer risk among postmenopausal women.

PubMed

Jung, Su Yon; Barrington, Wendy E; Lane, Dorothy S; Chen, Chu; Chlebowski, Rowan; Corbie-Smith, Giselle; Hou, Lifang; Zhang, Zuo-Feng; Paek, Min-So; Crandall, Carolyn J

2017-03-01

Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship. A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014. To assess bioactive IGF-I as a mediator of race-cancer relationship, we used the Baron-Kenny method and quantitative estimation of the mediation effect. Compared with white women, AA women had higher IGF-I levels; their higher risk of CR cancer, after accounting for IGF-I, was no longer significant. IGF-I was associated with breast and CR cancers even after controlling for race. Among viscerally obese (waist/hip ratio >0.85) and overall nonobese women (body mass index <30), IGF-I was a strong mediator, reducing the racial disparity in both cancers by 30% and 60%, respectively. In E-only users and nonusers, IGF-I explained the racial disparity in CR cancer only modestly. Bioavailable IGF-I is potentially important in racial disparities in obesity-related breast and CR cancer risk between postmenopausal AA and white women. Body fat distribution and E use may be part of the interconnected hormonal pathways related to racial difference in IGF-I levels and obesity-related cancer risk.

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

PubMed

Awada, A; Dirix, L; Manso Sanchez, L; Xu, B; Luu, T; Diéras, V; Hershman, D L; Agrapart, V; Ananthakrishnan, R; Staroslawska, E

2013-01-01

Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Impact of the mode of detection on outcome in breast cancer patients treated with breast-conserving therapy.

PubMed

Kini, V R; Vicini, F A; Victor, S J; Dmuchowski, C F; Rebner, M; Martinez, A A

1999-10-01

The impact of the mode of detection on outcome in patients with early stage breast cancer treated with breast-conserving therapy (BCT) was reviewed. Between January 1980 and December 1987, 400 cases of stage I and II breast cancer were treated with BCT. All patients underwent an excisional biopsy, external beam irradiation (RT) to the whole breast (45-50 Gy), and a boost to 60 Gy to the tumor bed. One hundred twenty-four cases (31%) were mammographically detected, whereas 276 (69%) were clinically detected. Median follow-up was 9.2 years. Patients whose cancers were detected by mammography more frequently had smaller tumors (90% T1 vs. 62%, p < 0.0001), lower overall disease stage (78% stage I vs. 47%, p < 0.0001), were older at diagnosis (78% >50 years vs. 54%, p < 0.001), less frequently received chemotherapy (8% vs. 21%, p = 0.001), and had an improved disease-free survival (DFS) (80% vs. 70%, p = 0.014), overall survival (OS) (82% vs. 70%, p = 0.005), and cause-specific survival (CSS) (88% vs. 77%, p = 0.003) at 10 years. However, controlling for tumor size, nodal status, and age, no statistically significant differences in the 5- and 10-year actuarial rates of local recurrence (LR), DFS, CSS, or OS were seen based on the mode of detection. Initial mode of detection was the strongest predictor of outcome after a LR. The 3-year DFS rate after LR was significantly better in initially mammographically detected versus clinically detected cases (100% vs. 61%, p = 0.011). Patients with mammographically detected breast cancer generally have smaller tumors and lower overall disease stage at presentation. However, the mode of detection does not independently appear to affect the success of BCT in these patients.

Adaptive Randomization of Neratinib in Early Breast Cancer.

PubMed

Park, John W; Liu, Minetta C; Yee, Douglas; Yau, Christina; van 't Veer, Laura J; Symmans, W Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B; Chien, A Jo; Wallace, Anne M; Boughey, Judy C; Haddad, Tufia C; Chui, Stephen Y; Kemmer, Kathleen A; Kaplan, Henry G; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S; Edmiston, Kirsten K; Elias, Anthony D; Northfelt, Donald W; Pusztai, Lajos; Moulder, Stacy L; Lang, Julie E; Viscusi, Rebecca K; Euhus, David M; Haley, Barbara B; Khan, Qamar J; Wood, William C; Melisko, Michelle; Schwab, Richard; Helsten, Teresa; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Esserman, Laura J; Berry, Donald A

2016-07-07

The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54

Weight changes and lifestyle behaviors in women after breast cancer diagnosis: a cross-sectional study.

PubMed

Yaw, Yong Heng; Shariff, Zalilah Mohd; Kandiah, Mirnalini; Mun, Chan Yoke; Yusof, Rokiah Mohd; Othman, Zabedah; Saibul, Nurfaizah; Weay, Yong Heng; Hashim, Zailina

2011-05-13

Weight gain rather than weight loss often occurs after breast cancer diagnosis despite breast cancer survivors frequently reported making healthful lifestyle changes. This study describes the prevalence and magnitude of changes in weight before and after breast cancer diagnosis and examines lifestyle behaviors of breast cancer survivors with stable weight, weight gain or weight loss. Respondents were 368 women with breast cancer characterized by stages I, II and III. All were recruited from hospitals or breast cancer support groups and had completed conventional treatment. Current weight and height were measured while weight at cancer diagnosis and 1 year before diagnosis were self-reported. Weight change was calculated as the difference between current weight and weight a year preceding breast cancer diagnosis. A 24-hour diet recall and Global Physical Activity Questionnaire assessed dietary intake and physical activity, respectively. Differences in lifestyle behaviors among weight change groups were examined using Analysis of Covariance (ANCOVA). Mean weight change from a year preceding diagnosis to study entry was 2.73 kg (95% CI: 1.90-3.55). Most women (63.3%) experienced weight gain rather than weight loss (36.7%) with a higher percentage (47.8%) having at least 5% weight gain (47.8%) rather than weight loss (22%), respectively. Compared to other weight change groups, women in >10% weight gain group had the lowest fruit and vegetable servings (1.58 servings/day; 95% CI: 1.36-1.82) and highest servings of dairy products (0.41 servings/day; 95% CI: 0.30-0.52). Weight gain was evident in this sample of women after breast cancer diagnosis. Information on magnitude of weight change after breast cancer diagnosis and lifestyle behaviors of breast cancer survivors with varying degrees of weight change could facilitate the development and targeting of effective intervention strategies to achieve healthy weight and optimal health for better survival.

Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland.

PubMed

Kiderlen, Mandy; Walsh, Paul M; Bastiaannet, Esther; Kelly, Maria B; Audisio, Riccardo A; Boelens, Petra G; Brown, Chris; Dekkers, Olaf M; de Craen, Anton J M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2015-01-01

Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted p<0.001), stage I (83% vs. 65%, p<0.001), stage II (80% vs. 74%, p<0.001) and stage III (74% vs. 57%, P<0.001) disease. On the other hand, more systemic treatment was provided in Ireland, where endocrine therapy was prescribed to 92% of hormone receptor-positive patients, compared to 59% in The Netherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer

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

ClinicalTrials.gov

2018-01-29

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

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

PubMed Central

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer. PMID:23183846

Surgical Treatment Differences Among Latina and African American Breast Cancer Survivors

PubMed Central

Campesino, Maureen; Koithan, Mary; Ruiz, Ester; Glover, Johanna Uriri; Juarez, Gloria; Choi, Myunghan; Krouse, Robert S.

2012-01-01

Purpose/Objectives To describe breast cancer treatment choices from the perspectives of Latina and African American breast cancer survivors. Design An interdisciplinary team conducted a mixed-methods study of women treated for stages I–IV breast cancer. Setting Participants’ homes in metropolitan areas. Sample 39 participants in three groups: monolingual Spanish-speaking Latinas (n = 15), English-speaking Latinas (n = 15), and African American women (n = 9). Methods Individual participant interviews were conducted by racially and linguistically matched nurse researchers, and sociodemographic data were collected. Content and matrix analysis methods were used. Main Research Variables Perceptions of breast cancer care. Findings High rates of mastectomy were noted for early-stage treatment (stage I or II). Among the participants diagnosed with early-stage breast cancer, the majority of English-speaking Latinas (n = 9) and African American women (n = 4) received a mastectomy. However, the majority of the Spanish-speaking Latina group (n = 5) received breast-conserving surgery. Four factors influenced the choice of mastectomy over lumpectomy across the three groups: clinical indicators, fear of recurrence, avoidance of adjuvant side effects, and perceived favorable survival outcomes. Spanish-speaking Latinas were more likely to rely on physician treatment recommendations, and the other two groups used a shared decision-making style. Conclusions Additional study is needed to understand how women select and integrate treatment information with the recommendations they receive from healthcare providers. Among the Spanish-speaking Latina group, limited English proficiency, the use of translators in explaining treatment options, and a lack of available educational materials in Spanish are factors that influenced reliance on physician recommendations. Implications for Nursing Oncology nurses were notably absent in supporting the women’s treatment decision making

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

PubMed

Monstad, S E; Storstein, A; Dørum, A; Knudsen, A; Lønning, P E; Salvesen, H B; Aarseth, J H; Vedeler, C A

2006-04-01

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

Development of Patients' Decision Aid for Older Women With Stage I Breast Cancer Considering Radiotherapy After Lumpectomy

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

Wong, Jennifer; D'Alimonte, Laura; Angus, Jan

Purpose: To develop a patient decision aid (PtDA) for older women with Stage I, pathologically node negative, estrogen receptor-positive progesterone receptor-positive breast cancer who are considering adjuvant radiotherapy after lumpectomy and to examine its impact on patients' decision making. Methods and Materials: A PtDA was developed and evaluated in three steps according to the Ottawa Decision Support Framework: (1) needs assessment (n = 16); (2) Pilot I to examine PtDA acceptability (n = 12); and (3) Pilot II, a pretest posttest (n = 38) with older women with estrogen receptor-positive progesterone receptor-positive breast cancer after lumpectomy who were receiving adjuvantmore » radiation therapy. Measures included patients' satisfaction with the PtDA, self-reported decisional conflict, level of distress, treatment-related knowledge, and choice predisposition. Results: The PtDA is a booklet that details each adjuvant treatment option's benefits, risks, and side effects tailored to the patient's clinical profile; includes a values clarification exercise; and includes steps to guide patients towards their decision. On the basis of qualitative comments and satisfaction ratings, all women thought that the PtDA was helpful and informative. In comparison with their baseline scores, patients had a statistically significant (p < 0.05) reduction in decisional conflict (adjusted mean difference [AMD], -7.18; 95% confidence interval [CI], -13.50 to 12.59); increased clarity of the benefits and risks (AMD, -10.86; CI, -20.33 to 21.49); and improved general treatment knowledge (AMD, 8.99; CI, 2.88-10.28) after using the PtDA. General trends were also reported in the patients' choice predisposition scores that suggested potential differences in treatment decision after PtDA use. Conclusions: This study provides evidence that this PtDA may be a helpful educational tool for this group of women. The quality of care for older breast cancer patients may be enhanced by the

Computerized detection of breast cancer on automated breast ultrasound imaging of women with dense breasts

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

Drukker, Karen, E-mail: kdrukker@uchicago.edu; Sennett, Charlene A.; Giger, Maryellen L.

2014-01-15

Purpose: Develop a computer-aided detection method and investigate its feasibility for detection of breast cancer in automated 3D ultrasound images of women with dense breasts. Methods: The HIPAA compliant study involved a dataset of volumetric ultrasound image data, “views,” acquired with an automated U-Systems Somo•V{sup ®} ABUS system for 185 asymptomatic women with dense breasts (BI-RADS Composition/Density 3 or 4). For each patient, three whole-breast views (3D image volumes) per breast were acquired. A total of 52 patients had breast cancer (61 cancers), diagnosed through any follow-up at most 365 days after the original screening mammogram. Thirty-one of these patientsmore » (32 cancers) had a screening-mammogram with a clinically assigned BI-RADS Assessment Category 1 or 2, i.e., were mammographically negative. All software used for analysis was developed in-house and involved 3 steps: (1) detection of initial tumor candidates, (2) characterization of candidates, and (3) elimination of false-positive candidates. Performance was assessed by calculating the cancer detection sensitivity as a function of the number of “marks” (detections) per view. Results: At a single mark per view, i.e., six marks per patient, the median detection sensitivity by cancer was 50.0% (16/32) ± 6% for patients with a screening mammogram-assigned BI-RADS category 1 or 2—similar to radiologists’ performance sensitivity (49.9%) for this dataset from a prior reader study—and 45.9% (28/61) ± 4% for all patients. Conclusions: Promising detection sensitivity was obtained for the computer on a 3D ultrasound dataset of women with dense breasts at a rate of false-positive detections that may be acceptable for clinical implementation.« less

Breast cancer: descriptive profile of 80 women attending breast cancer care in the Department of General and Digestive Surgery of CHU-YO.

PubMed

Bambara, Hierrhum Aboubacar; Zouré, Abdou Azaque; Sawadogo, Alexis Yobi; Ouattara, Abdoul Karim; Ouédraogo, Nabonswindé Lamoussa Marie; Traoré, Si Simon; Bakri, Youssef; Simpore, Jacques

2017-01-01

Breast cancer is a common cause of death among women in Burkina Faso. The aim of this study was to determine a descriptive profile of 80 women and establish a description of risk factors associated with breast cancer in these women. This cross-sectional study recruited women with breast cancer in Ouagadougou. Teaching Hospital Yalgado Ouedraogo in Burkina Faso from January 2015 to February 2016. We have collected data on socio-demographic characteristics, reproductive status, clinical information, treatment and molecular characteristics. The average age of the study population was 48.2±12.4 years. Family history of breast cancer was reported in 18.75% of the studied participants against 16.25% family history for other types of cancer. Patients from urban areas represented 87.5% of our studied population with 58.75% of household, multiparous (55.0%), no aborts status (56.2%), post-menopausal women (53.75%), no oral contraception (63.75%), regular menstrual cycle (71.25%) and the prevalence of obesity was 12.5%. The clinical and molecular characteristics showed that left-sided breast cancer accounted for 51.25 %, high grade (II and III) represented 93.75 % of cases and the majority of tumors were infiltrating ductal carcinomas (93.75%) with stages III and IV accounted for 50.0%. This study described the distribution of risks factors in a population of breast cancer women. Although more research are needed to support these findings, a clear understanding of risk factors associated with breast cancer would contribute to significantly reduce breast cancer incidence and mortality in Burkina Faso.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

PubMed

Berlière, M; Roelants, F; Watremez, C; Docquier, M A; Piette, N; Lamerant, S; Megevand, V; Van Maanen, A; Piette, P; Gerday, A; Duhoux, F P

2018-02-01

In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

PubMed

Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

2017-08-20

Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant

Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

ClinicalTrials.gov

2018-04-17

Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma