History Of Benign Breast Disease Research Articles

A case-control study on the risk factors of recurrence and metastasis in breast cancer

Objective To explore the risk factors of breast cancer recurrence for the cause exploration and prevention of the disease. Methods With matched case-control method, a survey was conducted among survival cases of histologically diagnosed breast cancer patients in Southern hospital from January 2004 to December 2007 in Guangzhou city. The survival cases were divided into case group and control group according to the inclusion criteria. Unconditional logistic model was used to analyze the data. Results Multiple factors logistic regression analysis showed mental stimulations [OR =10.926, 95%CI (5.041-23.682) ], oral contraceptive pills history [OR=2.634, 95%CI(1.548-4.482) ], benign breast disease history [OR=5.183, 95%CI(2.100-12.790) ], human epiderma growth factor receptor-2 (HER2) positive [OR= 2.257, 95%CI (1.326-3.843) ], lymph node metastasis [OR=2.021, 95%CI (1.272-3.212) ], distant metastasis [OR=3.718, 95%CI (2.125-6.503) ] might be associated with the increasing breast cancer recurrence risk. Regular exercise [OR=0.460, 95%CI(0.234-0.905) ], low stage of disease [OR=0.106, 95%CI(0.022-0.498) ], breast nursing time [OR=0.053, 95%CI(0.009-0.316) ], dietary intake of soy isflavones[OR=0.154, 95%CI (0.032 -0.745) ] might be associated with the decreasing breast cancer recurrence risk. Conclusions Clinical medical staff should take attention to the breast cancer who had benign breast disease history to ensure timely check-ups, early detection, early diagnosis and early treatment. Improving physical and psychological quality, reducing oral contraceptive pills, prolonging breast nursing time, and increasing dietary intake of soy isflavones were important to the prevention of breast cancer recurrence. Key words: Breast neoplasms; Recurrence; Risk factors; Case-control studies

Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors.

We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors, including body mass index (BMI), age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. This study included 1,044 postmenopausal incident breast cancer cases diagnosed within the Nurses' Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense, and non-dense areas were measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Percent breast density was more strongly associated with breast cancer risk in current postmenopausal hormone users (≥50 vs. 10%: OR 5.34, 95% CI 3.36-8.49) as compared to women with past (OR 2.69, 95% CI 1.32-5.49) or no hormone history (OR 2.57, 95% CI 1.18-5.60, p-interaction=0.03). Non-dense area was inversely associated with breast cancer risk in parous women, but not in women without children (p-interaction=0.03). Associations of density with breast cancer risk did not differ by the levels of BMI, age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. Women with dense breasts, who currently use menopausal hormone therapy are at a particularly high risk of breast cancer. Most breast cancer risk factors do not modify the association between mammographic breast density and breast cancer risk.

Abstract B39: Clinical characteristics of breast cancers in African American women with benign breast disease: A comparison to the Surveillance, Epidemiology and End Results Program

Abstract Although the association between benign breast disease (BBD) and risk of subsequent breast cancer is well-established, no previous studies have compared characteristics of breast cancers in women with a history of BBD to characteristics of cancers in the general population. In this study, we compared the characteristics of 109 breast cancers that developed in a population of African-American women with a history of benign breast disease (BBD population) to 10,601 breast cancers that developed in a general population of African-American women whose cancers were recorded by the Metropolitan Detroit Cancer Surveillance System (MDCSS population). The populations were compared on demographic characteristics such as age, marital status, and previous cancers, as well as clinical characteristics such as tumor hormone receptor status, grade, stage, behavior, size, and treatment. Overall and breast cancer-specific survival were also compared between populations. Women in the BBD population developed lower grade, earlier stage cancers that were more likely to be hormone receptor-positive and less likely to exhibit invasive behavior. Women in the BBD population were also significantly less likely to die from breast cancer after ten years of follow-up. These results suggest that although women with a history of BBD are at greater breast cancer risk, their breast cancers may be more likely to be detected early, leading to better breast cancer-specific survival. Citation Format: Susanna D. Mitro, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay, Baraa Alosh, Bassam Albashiti, Quratulain Ahmed, Derek C. Radisky, Marlene H. Frost, Amy C. Degnim, Julie J. Ruterbusch, Michele L. Cote. Clinical characteristics of breast cancers in African American women with benign breast disease: A comparison to the Surveillance, Epidemiology and End Results Program. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B39. doi:10.1158/1538-7755.DISP13-B39

Abstract 264: Breast cancer incidence and Gail risk in a prospective study of women with benign breast disease

Abstract Introduction: Women with benign breast disease (BBD) are at an increased risk of subsequent development of breast cancer. We followed a cohort of high-risk women to investigate the development of invasive breast cancer and examined differences in incidence and Gail risk among women with and without BBD. Methods: The Women At Risk (WAR) registry is a prospectively followed cohort of women at Columbia University medical Center from 1991 to 2011. Ascertainment of progression from BBD to breast cancer was done through examination of medical records and New York Presbyterian tumor registry. Incidence rates are reported per 10,000 person-years at risk. Women with a history of BBD at baseline were diagnosed with BBD prior to enrollment in the WAR registry, women with BBD diagnosed after enrollment were classified as incident BBD. We calculated 5-year and lifetime Gail risk based on women's characteristics at baseline to compare Gail risk in women with and without BBD. For this analysis, women with incident BBD were excluded. We assessed risk of invasive breast cancer using Poisson regression analysis, with the log-transformed person-years as the offset. Results: There were 396 women with a history of BBD at baseline. Mean 5-year Gail risk was significantly higher for women with a history of BBD as compared to women without a history of BBD at baseline (BBD (Mean±Std): 3.60±2.29 vs. No BBD: 1.94±1.68, p<0.001). We identified 26 subsequent invasive breast cancers among 396 women with BBD at baseline and 47 breast cancers among 1,322 women without BBD, with a mean follow-up of 8.6 years. Among women with BBD at baseline breast cancer incidence is 100.8 per 10,000 women years, compared to 38.6 per 10,000 woman years among women without BBD. A diagnosis of BBD at baseline resulted in an excess incidence of 62.2 per 10,000 woman years. Age-adjusted risk of invasive breast cancer was 2.45 higher in women with BBD at baseline as compared to women without BBD (RR: 2.45, 95% CI: 1.52-3.96). The average time between BBD diagnosis and invasive breast cancer diagnosis was 9.0 years. Time to breast cancer diagnosis was similar regardless of histologic type (p=0.22). After follow-up, 844 women were diagnosed with incident BBD. We identified 48 invasive breast cancers among 844 women with incident BBD, with a breast cancer incidence of 65.6 per 10,000 woman years. Incident BBD results in an excess incidence of breast cancer of 35.2 per 10,000 woman years. Age-adjusted risk of invasive breast cancer was 1.76 higher in women with incident BBD as compared to women without BBD (RR: 1.76, 95% CI: 1.18-2.64). Conclusions: Breast cancer incidence is higher among women with BBD, contributing to the evidence of increased breast cancer risk after BBD diagnosis. Citation Format: Laura L. Reimers, Katherine D. Crew, Mary Beth Terry. Breast cancer incidence and Gail risk in a prospective study of women with benign breast disease. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 264. doi:10.1158/1538-7445.AM2014-264

Abstract 3280: Interaction between genetic variants in mTOR and body size on breast cancer risk in African-American and European-American women

Abstract Mammalian target of rapamycin (mTOR), a key protein in the phosphatidylinositol 3-kinase/Akt/mTOR (PI3K-AKT-mTOR) pathway promoting cell proliferation and angiogenesis, can be activated by overfeeding in animal models. However, epidemiological data on the mTOR pathway and breast cancer risk are very limited. We investigated the association of 13 single nucleotide polymorphisms (SNPs) in mTOR with breast cancer and potential effect modification of body size in the Women's Circle of Health Study (WCHS), a large case-control study in New York and New Jersey. Participants included 658 incident cases and 649 controls of European American background (EA) and 621 African-American (AA) cases and 744 matched controls, aged 20-75 y. Body size was approximated by body mass index (BMI) at recruitment measured by trained interviewers or obtained from self-report if the measurement was unavailable. Because allele frequencies varied between AAs and EAs, multivariable logistic regression was performed separately within groups, adjusting for age, family history, education, history of benign breast disease, cigarette smoking, proportion of European ancestry, and BMI (for main effects only). We observed higher risks of breast cancer associated with 3 SNPs in high linkage disequilibrium (r2 = 1) (rs2536 [3’-UTR], p=0.08; rs12116957 [intron], p=0.09; rs12125777 [intron], p=0.018) under a dominant genetic model among EA women. For rs12125777, variant allele carriers had a 71% higher breast cancer risk (odds ratio [OR]=1.71, 95% confidence interval (CI)=1.10-2.66) compared to non-carriers. The risk was more prominent among women who were overweight/obese (i.e., BMI ≥25 kg/m2; OR=3.34, 95% CI=1.67-6.69), compared to that among those with normal weight (OR=0.89, 95% CI=0.48-1.68; p-interaction=0.009). Compared to estrogen receptor (ER) positive cancers, the increased risk was more noticeable for ER negative cancers: the ORs comparing variant allele carriers to non-carriers were 2.68 (95% CI=1.24-5.79) overall, 8.49 (95% CI=2.85-25.3) among overweight/obese women, and 0.94 (95% CI=0.26-3.38) among normal-weight women; p-interaction=0.018. No association of genetic variants in mTOR with breast cancer was observed among AA women at a significant level of 0.1. Our findings suggest an etiologic role of overweight/obesity via promoting the mTOR pathway in breast carcinogenesis among EA women. Citation Format: Ting-Yuan D. Cheng, Jyoti Shankar, Gary Zirpoli, Song Yao, Michelle Roberts, Chi-Chen Hong, Elisa V. Bandera, Christine B. Ambrosone. Interaction between genetic variants in mTOR and body size on breast cancer risk in African-American and European-American women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3280. doi:10.1158/1538-7445.AM2014-3280

Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.

While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649) per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.

Role of Some Risk Factors in the Etiology of Breast Cancer in the Sudan

Aim: The aim of this study was to correlate breast cancer by common breast cancer risk factors in the Sudan. Methodology: Using a purposeful questionnaire 150 female breast cancer patients and 100 apparently health controls were asked detailed information on about risk factors. Results: Out of the 150 women with breast cancer, 38 (25.3%), 22(14.7%), 26(17.3%), 20(13.3%), 21(14%), 11(7.3%), 72(48%), and 86(57.3%) were identified as having a previous history of oral contraceptives usage, a family history of breast cancer, a past history of benign breast disease, a previous history of breast cancer, a previous breast biopsy, claimed other cancers in their families, confessed a pesticides exposure, and over weigh in most of their lives respectively. Out of the 150 women, 44(29.3%) were found to have a previous physical activity. Moreover, 44.8% and 66.9% have attended the menarge at the age of 13 and 14 respectively. Of these factors, statistical significant risks were found with, past history of benign breast disease (P < 0.04), previous breast biopsies (P <0.07), pesticides and plasticizers exposure (P < 0.01 and 0.04), period of being over weight (P <0.001), practice physical activities (P <0.0001), unmarried (P <0.002), decreased number of children (P <0.002). According to the ethnic group, Gaalyaeen tribes represented 61(40.7%) of the study subjects. Most of the patients were from Khartoum state, constituting 37.3%. Conclusion: There was variable exposure to many risk factors for breast cancer in the Sudan. The study suggests further separate measurement of risk factors for breast cancer, as well as, factors that might reduce those risk factors. Cohort mean of evaluation is highly recommended.

Benign breast and gynecologic conditions, reproductive and hormonal factors, and risk of thyroid cancer.

The higher incidence of thyroid cancer in women compared with men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50 to 78 years old, we prospectively examined associations of self-reported history of benign breast and gynecologic conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated in models using age as the time metric. During follow-up (median, 11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years; HR, 2.24; 95% CI, 1.20-4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles; HR, 2.40; 95% CI, 1.33-4.30), greater number of live births (≥5 vs. 1-2; HR, 1.72; 95% CI, 1.05-2.82), and history of uterine fibroids (HR, 1.72; 95% CI, 1.18-2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were nonsignificantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.

Alcohol intake between menarche and first pregnancy: a prospective study of breast cancer risk.

BackgroundAdult alcohol consumption during the previous year is related to breast cancer risk. Breast tissue is particularly susceptible to carcinogens between menarche and first full-term pregnancy. No study has characterized the contribution of alcohol consumption during this interval to risks of proliferative benign breast disease (BBD) and breast cancer.MethodsWe used data from 91005 parous women in the Nurses’ Health Study II who had no cancer history, completed questions on early alcohol consumption in 1989, and were followed through June 30, 2009, to analyze breast cancer risk. A subset of 60093 women who had no history of BBD or cancer in 1991 and were followed through June 30, 2001, were included in the analysis of proliferative BBD. Relative risks (RRs) were estimated using Cox proportional hazard regression.ResultsWe identified 1609 breast cancer cases and 970 proliferative BBD cases confirmed by central histology review. Alcohol consumption between menarche and first pregnancy, adjusted for drinking after first pregnancy, was associated with risks of breast cancer (RR = 1.11 per 10g/day intake; 95% confidence interval [CI] = 1.00 to 1.23) and proliferative BBD (RR = 1.16 per 10g/day intake; 95% CI = 1.02 to 1.32). Drinking after first pregnancy had a similar risk for breast cancer (RR = 1.09 per 10g/day intake; 95% CI = 0.96 to 1.23) but not for BBD. The association between drinking before first pregnancy and breast neoplasia appeared to be stronger with longer menarche to first pregnancy intervals.ConclusionsAlcohol consumption before first pregnancy was consistently associated with increased risks of proliferative BBD and breast cancer.

Abstract 3637: Repressive histone marks in breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study.

Abstract Repressive histone tail modifications have been previously characterized in breast cancer, but the relationship between these marks, tumor features and breast cancer molecular subtypes has not been studied in depth. We have tissue microarray data with marker information on 971 incident breast cancers that developed from 1976-2000 in women enrolled in the Nurses’ Health Study. Tissue microarray sections were stained for repressive H3K9 trimethylation (H3K9me3) and H3K27 trimethylation (H3K27me3) marks, and tumors with 50% or more positively stained cells were scored as histone mark positive. We found that 73.3% of tumors were H3K9me3 positive, and 84.9% of tumors were H3K27me3 positive. The relationships between histone marks and tumor features (tumor size, grade, stage, nodal involvement and hormone receptor status) were analyzed. While we found no association between H3K9me3 and tumor features, age-adjusted analyses suggested that H3K27me3 was associated with lower grade tumors (OR=5.51, 95% CI 2.64-11.50), p&amp;lt;0.0001), estrogen receptor-positive (ER+) tumors (OR=2.40, 95% CI 1.54-3.74, p=0.0001) and progesterone receptor-positive (PR+) tumors (OR=1.96, 95% CI 1.31-2.93, p=0.0012). In multivariate analyses, a strong association was observed between H3K27me3 and lower grade comparing grade 1 to grade 3 tumors as the referent (OR=5.17, 95% CI 2.12-12.62, p=0.0003) after adjusting for age at diagnosis, age at menarche, age at menopause, parity or age at first birth, family history of breast cancer in a first-degree relative, personal history of benign breast disease, menopausal status or PMH use, BMI at age 18, alcohol consumption, lactation and smoking. We also found associations between H3K27me3 and ER+ tumors (OR= 2.28, 95% CI 1.32-3.93, p=0.003) and with PR+ tumors (OR=2.14, 95% CI 1.30-3.50) in the fully adjusted model. The relationships between histone marks and breast cancer molecular subtypes were also analyzed. Molecular subtypes were defined using immunohistochemistry staining for markers, and grade. H3K27me3 was associated with Luminal A subtype compared to all other subtypes as the referent (OR=2.16, 95% CI 1.41-3.32, p=0.0004) in age-adjusted analyses and remained significant in the fully adjusted model (OR=1.72, 95% CI 1.04-2.88, p=0.0359). Our results indicate that H3K27me3, but perhaps not H3K9me3, is independently associated with lower grade and ER+ tumors. Our results are also suggestive of a relationship between H3K27me3 and Luminal A subtype. Overall, our findings indicate that repressive histone marks may influence specific tumor features and molecular pathways in breast cancer etiology, which may help to explain the basis of disease heterogeneity and further elucidate aberrant epigenetic mechanisms in breast cancer. Citation Format: Megan A. Healey, Andrew H. Beck, Stuart J. Schnitt, Rulla M. Tamimi, Aditi Hazra. Repressive histone marks in breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3637. doi:10.1158/1538-7445.AM2013-3637

Non-Practice of Breast Self Examination and Marital Status are Associated with Delayed Presentation with Breast Cancer

Delay in seeking treatment for breast cancer is a barrier to the early diagnosis and management of the disease, resulting in a poorer prognosis. We here estimated the prevalence of delayed presentation for breast cancer and identified possible influential sociodemographic factors in a cross-sectional study of 250 patients diagnosed with primary breast cancer at the Radiotherapy and Oncology Clinic in Kuala Lumpur Hospital. Data were collected by face-to-face interview using a structured questionnaire and from medical records. We examined associations between delayed presentation (presenting to a physician more than 3 months after self-discovery of a symptom) and sociodemographic characteristics, practice of breast self examination (BSE), history of benign breast disease, family history of breast cancer and type of symptom, symptom disclosure and advice from others to seek treatment using multiple logistic regression. Time from self-discovery of symptom to presentation ranged from tghe same day to 5 years. Prevalence of delayed presentation was 33.1% (95%CI: 27.4, 39.3). A significantly higher proportion of delayers presented with late stages (stage III/IV) (58.3% vs. 26.9%, p<0.001). Divorced or widowed women (OR: 2.23, 95% CI: 1.11, 4.47) had a higher risk of delayed presentation than married women and women who never performed breast self examination were more likely to delay presentation compared to those who regularly performed BSE (OR: 2.74, 95% CI: 1.33, 5.64). Our findings indicate that delayed presentation for breast cancer symptoms among Malaysian women is high and that marital status and breast self examination play major roles in treatment-seeking for breast cancer symptoms.

Abstract P4-13-04: Estrogen and Avoidance of Invasive Breast Cancer, Coronary Heart Disease and All-cause Mortality. Public Health Impact of Estrogen Guidelines for Women entering Menopause.

Abstract BACKGROUND. Estrogen [E] for women entering menopause is not perceived beneficial for either iBrCa or CHD. However, data from RCTs suggest that use of Estrogen reduces: a. rates of invasive breast cancer [iBrCa], andb. atherogenesis, vessel pathology and in certain age groups, coronary heart disease [CHD]. OBJECTIVES: To estimate the population-level impact of Estrogen as part of hormone replacement therapy [HRT] for women entering menopause on rates of iBrCa, CHD and all cause mortality [AC- Mort] that could result from a change of Practice where Estrogen would be recommended for women entering menopause. METHODOLOGY. Annualized rates of iBrCa, CHD and AC-Mort in women age 50–59, and annualized iBrCa rates for all participants and those without Past History of Benign Breast Disease [PHBBD] extracted from the results of the Women's Health Initiative trial [E] alone vs placebo [Refs 1,2], were applied to estimate the reduction in the Number of Avoided Events per 100,000 female population per annum [NAE]. The [NAE] over 10 years follow up was calculated as: NAE = (P − E) × 100,000 × 10 where P was the annualized rate among placebo participants and E was the annualized rate among Estrogen participants. RESULTS. [Table 1]. Taking 100,000 exposed versus unexposed women age 50–59, and rate reduction due to [E] of −41% [HR=0.59], −20% [HR=0.80] and −27% [HR=0.73] for CHD, iBrCa and AC-Mort [Ref 1,2], respectively, there will be annual avoidance of −130 cases of CHD, −60 of iBrCa, and −130 of deaths from any cause. iBrCa annual avoidance for women any age, and those without PHBBD, were −80 and −150 events, respectively. CONCLUSION. 1. Estrogen therapy could reduce thousands of BrCa, CHD and AC-Mortality events annually, just in North America. These gains are in addition to the established quality of life improvement for millions of women due to [E]. 2. Of particular importance is the [E] effect on reduction of iBrCa rates, particularly significant for women without PHBBD, confirming the new paradigm of Dual E effect for human BrCa [Ref 3]. 3. These substantial Public Health gains associated with [E] may justify changing policy to incorporate [E] into HRT guidelines for appropriately selected women. 4. Accelerated research to optimize [E] formulations, and identifying subsets that benefit most, is urgently required for optimum HRT use in Prevention of iBrCa, CHD, and reducing AC- mortality. REFERENCES 1. LaCroix AZ, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 2011;305:1305–14. 2. Anderson GL, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial Lancet Oncol 2012;13:476–86. 3. Ragaz J, et al. Dual estrogen effects on breast cancer: endogenous estrogen stimulates, exogenous estrogen protects. Further investigation of estrogen chemoprevention is warranted. Cancer Res 2010;70. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-04.

Gene-Environment Interactions for Breast Cancer Risk Among Chinese Women: A Report From the Shanghai Breast Cancer Genetics Study

Genome-wide association studies have identified approximately 20 susceptibility loci for breast cancer. A cumulative genetic risk score (GRS) was constructed from 10 variants with replicated associations among participants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996-1998 and 2002-2005). Interactions between the GRS and 11 breast cancer risk factors were evaluated. Among the 6,408 study participants, no evidence of effect modification was found with the GRS for age at menarche, age at menopause, age at first live birth/parity, total months of breastfeeding, family history of breast cancer, history of benign breast disease, hormone replacement therapy, body mass index, waist/hip ratio, or regular physical activity. The effect of the GRS was least homogeneous by duration of menstruation; further analysis indicated a nominally significant interaction with one genetic variant. The mitochondrial ribosomal protein S30 gene (MRPS30) rs10941679 was associated with breast cancer risk only among women with more than 30 years of menstruation (odds ratio = 1.15, 95% confidence interval: 1.05, 1.26). Although this multiplicative interaction reached a nominal significance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study revealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer.

Risk factors related to female breast cancer in regions of Northeast China: a 1:3 matched case-control population-based study.

There has been an increase in the incidence of breast cancer in China, but no definite risk and protective factors for breast cancer have been identified in Chinese females. This study was designed to identify the risk factors for female breast cancer in North and East China. A 1:3 matched, case-control study was conducted. All of the subjects in the case and control groups were selected from a previous epidemiological survey of 122 058 females aged 25 to 70 years. Single and multiple Logistic regression analyses were used to study potential factors in the development of breast cancer. Significant differences at the level of α=0.20 between case and control groups were observed for the following factors: economic status, social status, family annual income, bean product consumption, body mass index (BMI), family history of breast cancer in the first or second degree, number of miscarriages, menstrual pattern, benign breast disease history, nipple leakage, inverted nipple, history of diabetes mellitus, history of hypertension, history of ovarian cyst, physical exercise, current and global quality of life satisfaction, healthy behavior and prevention, and scores of breast cancer-related knowledge. After Cox-regression model analysis (α=0.10), six factors were found to be significantly related to breast cancer, of which the ORs and 95%CIs were: BMI, 1.696 (1.169-2.460, P=0.005); benign breast disease history, 2.672 (0.848-8.416, P=0.093); family history of breast cancer, 7.080 (1.758-28.551, P=0.006); number of miscarriages, 1.738 (1.014-2.978, P=0.044); global quality of life satisfaction, 3.044 (1.804-5.136, P=0.000); healthy behavior and prevention, 3.294 (1.692-6.412, P=0.000). A comprehensive range of factors related to breast cancer was identified. Women should be educated about a healthy lifestyle, especially those with a family history of breast cancer or a personal history of benign breast disease.

Socio-demographic factors and reasons associated with delay in breast cancer presentation: A study in Nigerian women

We evaluated the effects of selected socio-demographic factors on late presentation and reasons why our breast cancer patients delay reporting for treatment. All female breast cancer patients referred to one of the general surgery out-patient clinics of Lagos State University Teaching Hospital between January 2009 and December 2010 were interviewed. Relevant socio-demographic and clinical data were obtained and reasons for patient delay documented. Univariate and multivariate logistic regression analyses were conducted to calculate odd ratio for delay. A total of 201 patients were enrolled. Mean duration of symptoms was 12.12 months (SD ± 5.18). Delay for more than 3 months before initial medical consultation was observed in 164 patients (81.6%). Increased risk of late presentation was associated with single women (OR = 2.054), primary level of education (OR = 3.059), negative history of benign breast disease (OR = 1.648) and pre-menopause (OR = 1.861). Ignorance of the nature of illness, belief in spiritual healing, fear of mastectomy and belief in herbal treatment were the leading reasons for delay. Women with higher risk of late presentation should be the target group during interventions aimed at raising breast cancer awareness. Reasons for patient delay should also be addressed.

P4-10-09: Hormone Replacement Therapy: A Benign Breast Disease's Risk?

Abstract Background Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer. However relations between use of HRT and benign breast lesions remain contradictory (1-3). Our goal was to investigate whether HRT and its duration use are associated with benign breast lesions. Materials &amp; Methods From 2001 to 2007, 2708 patients with a non palpable breast lesion were referred to our breast care center. Radiological abnormalities were screened either by breast ultrasound mammography, or MRI. Of those, 1 329 patients had a biopsy in our Radiology Unit. We focus on the postmenopausal women (n=739). Clinical data including HRT use extent were reported. Patients with previous history of benign breast disease or malignancy were excluded. Results The analysis was performed on 739 patients. Biopsies yielded a benign result in 414 (56%) of them (fibroadenoma n=71, blunt duct adenosis n=94, fibrocystic disease n=92, epithelial hyperplasia n=56, others n=101), high risk lesions in 57 (8%) (atypical ductal hyperplasia n=28, atypical lobular hyperplasia n=19, lobular carcinoma in situ n=10) and malignancy in 268 (36%) (not studied here). For the 471 patients with benign or high risk breast lesion, the median age was 59 years, 80% had at least one pregnancy and 27% had a family history of breast cancer. Among these 471 patients, 47% of them had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 2 years. The HRT use was not significantly associated with the type of benign or high risk breast disease. No association was observed either between breast disease and duration of HRT (less or more than 7 years respectively).Older age was significantly correlated to atypia or carcinoma (median age at diagnosis 59 y.o in benign lesions, 60 y.o in high risk lesions and 62 y.o in malign lesions, with significant difference) (p&amp;lt;0,0001). Conclusion In this study of postmenopausal women, HRT and its duration use were not associated with the type of benign or high risk breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of HRT use is small, if ever it exists. 1. Finkelde DT, Kitchen PR, Hayes PR, McKinlay MR, Henderson MA 2001 Symptomatic benign breast disease and hormone replacement therapy. Breast 10:127–130 2. Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J 2003 Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Eur J Cancer 39:1738–1745 3. Rohan TE, Miller AB 1999 Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast. Eur J Cancer Prev 8:123–130 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-09.

Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger

Differences in incidence, prognosis, and treatment response suggest gene expression patterns may discern breast cancer subtypes with unique risk factor profiles; however, previous results were based predominantly on older women. In this study, we examined similar relationships in women ≤ 56 years, classified by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 for 890 breast cancer cases and 3,432 frequency-matched population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) for tumor subtypes were calculated using multivariate polytomous regression models. A total of 455 (51.1%) tumors were considered luminal A, 72 (8.1%) luminal B, 117 (13.1%) non-luminal HER-2/neu+, and 246 (27.6%) triple negative. Triple negative tumors were associated with breast feeding duration (per 6 months: OR = 0.76, 95% CI 0.64-0.90). Among premenopausal women, increasing body size was more strongly associated with luminal B (OR = 1.73, 95% CI 1.07-2.77) and triple negative tumors (OR = 1.67, 95% CI 1.22-2.28). A history of benign breast disease was associated only with increased risk of luminal A tumors (OR = 1.89, 95% CI 1.43-2.50). A family history of breast cancer was a risk factor for luminal A tumors (OR = 1.93, 95% CI 1.38-2.70) regardless of age, and triple negative tumors with higher risks for women <45 (OR = 5.02, 95% CI 2.82-8.92; P for age interaction = 0.005). We found that little-to-no breastfeeding and high BMI were associated with increased risk of triple negative breast cancer. That some risk factors differ by molecular subtypes suggests etiologic heterogeneity in breast carcinogenesis among young women.

Abstract 3723: Predicting breast cancer risk to age 80: A clinical tool

Abstract While numerous models of breast cancer risk have been developed, few are used in routine clinical care. Thus women are not advised of potential strategies to reduce their future risk of breast cancer; either SERMS for high risk women or weight control and physical activity, reduction in alcohol or other approaches for moderate risk women. Furthermore, few models incorporate the full range of known risk factors and provide easy access for clinical use. The Rosner-Colditz log incidence model of breast cancer was developed and validated on independent data sets within Nurses’ Health Study cohort 1. The model includes a full range of reproductive and lifestyle risk factors for breast cancer. We now have developed a tool for batch or individual data input that provides 5-year risk, and risk to age 80. Input variables include current age, weigh at age 18, current weight, height, current alcohol intake and at age 18, age at menarche, age at menopause and type of menopause, family history of breast cancer and history of benign breast disease, hormone use (current, past, never) and type of hormone used, duration of postmenopausal hormone use, and age at each birth. Parameter estimates are drawn from Nurses’ Health Study data where we have shown the model performs with higher predictability (area under the ROC curve was 0.623) significantly better than the Gail model (area under the ROC 0.578) (p&amp;lt;0.001). For the total cohort, Incidence of invasive breast cancer in the NHS is consistent with SEER data (O/E = 1.0; 95%CI 0.98-1.03). For clinical use, risk estimates are adjusted for US mortality to provide incidence estimates to age 80 that account for competing risks. Clinical application requires assumptions regarding future weight change, duration of continued use of hormone therapy, and for premenopausal women, future age at menopause. 1. Colditz G, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses’ Health Study. Am J Epidemiol. 2000;152(10):950-964. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3723. doi:10.1158/1538-7445.AM2011-3723

Relationship between polymorphism of ErbB4 gene in mirco-RNA binding site and the risk for breast cancer

Objective: To investigate the relationship between single nucleotide polymorphism (SNP) of ErbB4 gene in mirco-RNA binding site and the susceptibility of breast cancer. Methods: Genotypes of ErbB4 gene in mirco-RNA binding site at rs1595066 and rs16845990 were measured using the TaqMan SNP method in 1 509 patients with breast cancer and 1 517 healthy controls. Results: Three kinds of genotype of ErbB4 gene in mirco-RNA binding site at rs1595066 were significantly different between breast cancer patients and the healthy controls (P＝0.045), while there was no difference at rs16845990 site (P＝0.302). The carriers of AG and AA genotypes at rs1595065 site had lower risk of breast cancer than GG genotype [(odds ratio, OR) = 0.81, 95% (confidence interval, CI) = 0.69-0.95; OR = 0.75, 95% CI = 0.58-0.96]. Stratified analysis showed that this protective effect was significant in the subjects aged over 55 years, without a history of benign breast disease and without a family history of cancer. Conclusion: The polymorphism of rs1595066 G＞A in micro-RNA binding site of ErbB4 gene may be associated with the reduction risk of breast cancer. DOI:10.3781/j.issn.1000-7431.2011.03.009

Abstract P3-11-10: Risk Factors for Pregnancy-Associated Breast Cancer: A Report from the Nigerian Breast Cancer Study

Abstract Background: It is known that pregnancy has a dual effect on breast cancer risk, with increased risk of breast cancer in short term and decreased risk in the long run. Pregnancy-associated breast cancer (PABC), occurring during pregnancy and several years postpartum, has poor prognosis and is challenging in clinical management. However, risk factors for PABC, except for pregnancy per se, are less understood. Other reproductive factors including age at menarche and age at first live birth may play important roles in the development of PABC. Methods: The study is based on the Nigerian Breast Cancer Study, a case-control study of breast cancer conducted in Ibadan, Nigeria, between 1998 and 2009. In-person interviews were conducted using structured questionnaires to collect detailed epidemiologic data. Pre-menopausal women who were 50 years old or younger were eligible to this analysis. The breast cancer cases were divided in two groups: PABC (diagnosed during pregnancy or within 5 years postpartum) and non-PABC. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI), contrasting each group of cases versus controls. Age in 3-year category, ethnicity, education, family history of breast cancer, history of benign breast disease, hormonal contraceptive use, alcohol drinking, height, and body mass index were adjusted in the multivariate models. Results: In total, 1440 women were eligible to this study, including 311 PABC cases, 357 non-PABC cases, and 772 healthy controls. In the multivariate analysis adjusting aforementioned potential confounders, age at menarche was inversely associated with non-PABC (p=0.002, Table 1) but only trend towards significance for PABC (p=0.12). Age at first live birth was associated with lower risk of non-PABC but was associated with elevated risk of PABC. Table 1. Odds ratios and 95% confidence intervals for PABC and non-PABC Conclusions: We found menarche at older age may be protective against all premenopausal breast cancer, but age at first live birth has different role in the development of pregnancy-associated breast cancer and other premenopausal breast cancer in Nigerian women. The findings suggest that the trend towards delayed child-bearing may increase in the occurrence of breast cancer complicated by pregnancy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-10.