Breast Cancer In First-degree Relatives Research Articles

Familial aggregation of early‐onset cancers in early‐onset breast cancer families

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.

Family history of breast cancer, mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

BackgroundThis study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density. MethodsWomen aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk. ResultsOf the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14). ConclusionFamily history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.

The Role of Mammography in Asymptomatic High Risk Women in Mosul City

Breast cancer is the most common carcinoma in women in the western world .Breast cancer is the leading cause of death in those aged 44-50years.This cross-sectional study was performed to evaluate the role of mammography in the detection of occult malignant breast lesions in high-risk women.The screened women were clinically asymptomatic for breast cancer.The study population was 238 high-risk women in Mosul city; over 13 months. The age range was (35-75) years; the mean age was (42.7 years) in (62.2%) of the total. Ten groups of high-risk women were identified:-Those with a previous history of modified radical mastectomy 89 (37.4)% , mammography was positive in eight cases (8.99%). Of those who have a positive family history of breast cancer in first-degree relatives 68 (28.7%), mammographically positive cases were six (8.8)%. For those with a positive family history of malignancy elsewhere in the body other than the breast 35 (14.8)%, mammography was positive in three (8.6%). Of those with conservative surgery for stage one breast cancer 19(7.98%) (4) cases (21.1%) three were mammographically positive (15.8%) in the ipsilateral breast, and one woman in her contralateral breast 5.3%. Nulliparous women about forty years old were 9 (3.8%), and only two were mammographically positive (22.2%).Patients who were subjected to surgery for ovarian tumors 8 (3.4%). Two were mammographically positive(25%). Patients with operations for benign ipsilateral breast lesions were five (2.1%), only one was mammographically positive (20%).Two obese ladies with bulky fatty breasts (0.84%), one of them was mammographically positive (50%). Patients with a history of hysterectomy for fibroids were 2(0.84%),only one was mammographically positive (50%).One woman 74 years old (0.42%) was mammographically positive (100%).Ultrasonography and mammography were performed for 387 breasts. The size of tumors detected was in the range of 4-10 millimeters with an average of 4.6millmeters.In conclusion, mammography is an X-ray picture of the breast and doctors use it for early screening programs for early detection of breast cancer, especially in high-risk women, sometimes two to three years before it can be felt.

Current Practices in the Pathologic Assessment of Breast Tissue in Transmasculine Chest Surgery.

No guidelines exist regarding management of breast tissue for transmasculine and gender-nonconforming individuals. This study aims to investigate the experiences and practices regarding perioperative breast cancer risk management among the American Society of Plastic Surgeons members performing chest masculinization surgery. An anonymous, online, 19-question survey was sent to 2517 U.S.-based American Society of Plastic Surgeons members in October of 2019. A total of 69 responses were analyzed. High-volume surgeons were more likely from academic centers (OR, 4.88; 95 percent CI, 1.67 to 15.22; p = 0.005). Age older than 40 years [ n = 59 (85.5 percent)] and family history of breast cancer in first-degree relatives [ n = 47 (68.1 percent)] or family with a diagnosis before age 40 [ n = 49 (71.0 percent)] were the most common indications for preoperative imaging. Nineteen of the respondents (27.5 percent) routinely excise all macroscopic breast tissue, with 21 (30.4 percent) routinely leaving breast tissue. Fifty-one respondents (73.9 percent) routinely send specimens for pathologic analysis. There was no significant correlation between surgical volume or type of practice and odds of sending specimens for pathologic analysis. High patient costs and patient reluctance [ n = 27 (39.1 percent) and n = 24 (35.3 percent), respectively] were the most often cited barriers for sending specimens for pathologic analysis. Six respondents (8.7 percent) have found malignant or premalignant lesions in masculinizing breast specimens. Large variation was found among surgeons' perioperative management of chest masculinizing surgery patients regarding preoperative cancer screening, pathologic assessment of resected tissue, and postoperative cancer surveillance. Standardization of care and further studies are needed to document risk, incidence, and prevalence of breast cancer in the transmasculine population before and after surgery.

Predictors of Breast Cancer Screening behavior in Women aged 20-69 Referred to Public Health Centers: A Cross-Sectional Study in Isfahan Province.

Background:Breast cancer is the most common cancer in women. Delay in the diagnosis of breast cancer is a major challenge that can lead to disease progression. Identifying the predictors of breast cancer screening behavior is necessary to promote early detection of breast cancer. This study aims to investigate the predictors of breast cancer screening behavior in women aged 20–69 referred to public health centers.Methods:This cross-sectional study was conducted on 17255 women aged 20–69 years old in Isfahan Province referred to Public Health Centers by the multi-stage random sampling method. data were collected based on the paper forms of women's care aged 20–69 at public health centers, Isfahan, Iran, in 2012. Using STATA 14, logistic regression was employed to explore predictors of breast cancer screening behavior at a 5% significance level.Results:The mean age of women was 36.75 ± 10.46. About 6006 (34.8%) of women had a history of breast self-examination, and among women aged over 40 years, 17.7% reported ever having a mammogram. The most important factors influencing breast self-examination were age 40–49 (OR = 1.18; 95% CI: 1.06-1.33), history of hormone consumption (OR = 1.23; 95% CI: 1.15-1.33), family history of breast cancer in first-degree relatives (OR = 14.22; 95% CI: 9.83-20.57. The most important factors influencing mammography were hormone consumption (OR = 1.26; 95% CI: 1.05-1.51), and family history of breast cancer in first-degree relatives (OR = 32.55; 95% CI: 20.08-52.70).Conclusions:Our findings indicated that the performance of breast self-examination and mammography was low. The frequency of BC screening behavior was higher among women with BC risk factors The results revealed the need for health authorities to pay attention to education in BC detection methods.

WOMEN WITH BREAST CANCER ATTENDED IN PUBLIC HOSPITAL FROM MACAPÁ, AMAPÁ

Breast cancer is a disease of epidemiological concern worldwide, being considered a serious public health problem. Although it is well established that early diagnosis and adequate treatment interfere with mortality rates and the prevalence of cancer, few data are available regarding the descriptive epidemiology of breast cancer in Brazil, as well as in the various states of the federation, as is the State of Amapá. The general objective was to characterize the risk factors of breast cancer patients treated at Hospital de Clínicas Dr. Alberto Lima (HCAL) from January 2012 to December 2017 in the city of Macapá, Amapá. Cases of breast cancer were reviewed, with an analysis of 194 medical records, and the following variables were studied: age, education level, histological type of the neoplasia, age at first delivery, menarche and menopause, breastfeeding time, alcohol intake, smoking, family history of breast cancer in first-degree relatives. It was noted that the age group most affected was between 41-50 years old and with an education level of elementary education. In these women, the most frequent characteristics were: age at first delivery between 13-20 years, menarche between 10-13 years, menopause from 41-50 years with a significant number of patients at menace (outside menopause), breastfeeding time between 2-22 and 23-42 months, both intervals with the same number of records; most did not drink alcohol, were not smokers and had no family history of first-degree relatives of breast cancer. In the cases studied, the most frequently diagnosed histological type was invasive ductal carcinoma.

A comparative study of breast cancer mass screening and opportunistic screening in Chinese women

Objective: To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer. Methods: This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants' characteristics and screening results of the two groups were compared by χ2 test, Fisher exact test or Wilcoxon rank-sum test. Results: A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ²=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ²=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ²=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ²=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ²=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ²=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ²=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ²=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ²=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ²=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ²=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ²=0.082, P=0.774). Conclusions: Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Evaluation of family history in terms of breast cancer in cases applying for breast ultrasonography

Introduction: The present study aims to investigate the family history of breast cancer in patients who underwent breast ultrasonography for any reason. Methods: Patients at any age who underwent breast ultrasonography examination in our clinic due to family history, complaints of a palpable mass in the breast–breast pain, and cancer screening over the age of 40 years were included in the study between 2019 and 2021. Regardless of whether there is an individual diagnosed with breast cancer in each case’s family, the degree of proximity was asked. Additionally, the age of the cases and whether they gave birth or not were questioned and recorded. Results: Of the 3783 breast ultrasonography patients, 349 had a family history of breast cancer. Breast cancer was diagnosed in one relative in 79% (n=276), in two relatives in 15.5% (n=54), in three relatives in 5% (n=17), and in four relatives in 0.5% (n=2) with breast cancer in 3% (n=10). Of the cases, 181 had breast cancer in first-degree relatives; 169, in second-degree relatives; and 48, in third-degree relatives. Discussion and Conclusion: Although the genetic transmission of breast cancer, which is the most common cancer in women, is high, it is possible to achieve a significant decrease in mortality and morbidity rates with early diagnosis, thanks to routine breast examination and imaging by all women with or without a family history of breast cancer.

Paraben Content in Adjacent Normal-malignant Breast Tissues from Women with Breast Cancer

ObjectiveAccumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life. To assess the role of parabens in this phenomenon, the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province, Iran. MethodsAdjacent normal-malignant breast tissue samples were obtained from 53 subjects. The parabens including methyl-paraben (MePB), ethyl-paraben (EtPB), propyl-paraben (PrPB), and butylparaben (BuPB) were extracted from the sample supernatant and then subjected to gas chromatography analysis. ResultsSome risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer. We observed a significant association for dose-response pattern of MePB [OR = 98.34 (11.43–185.2), P = 0.027] for both ER+ and PR+ women and MePB [OR = 164.3 (CI: 112.3–216.3), P < 0.001] for HER2+ women than women with negative receptors. The risk of 95-fold increase in MePB dose and 164-fold increase in ΣPBs dose were significant for women with hereditary breast cancer in first-degree relatives. ConclusionsThese results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

Race/Ethnicity and Accuracy of Self-Reported Female First-Degree Family History of Breast and Other Cancers in the Northern California Breast Cancer Family Registry.

Few studies have evaluated accuracy of self-reported family history of breast and other cancers in racial/ethnic minorities. We assessed the accuracy of cancer family history reports by women with breast cancer (probands) from the Northern California Breast Cancer Family Registry compared with 2 reference standards: personal cancer history reports by female first-degree relatives and California Cancer Registry records. Probands reported breast cancer in first-degree relatives with high accuracy, but accuracy was lower for other cancers. Sensitivity (percentage correctly identifying relatives with cancer) was 93% [95% confidence interval (CI), 89.5-95.4] when compared with the relatives' self-report of breast cancer as the reference standard and varied little by proband race/ethnicity and other demographic factors, except for marginally lower sensitivity for Hispanic white probands (87.3%; 95% CI, 78.0-93.1; P = 0.07) than non-Hispanic white probands (95.1%; 95% CI, 88.9-98.0). Accuracy was also high when compared with cancer registry records as the reference standard, with a sensitivity of 95.5% (95% CI, 93.4-96.9) for breast cancer, but lower sensitivity for Hispanic white probands (91.2%; 95% CI, 84.4-95.2; P = 0.05) and probands with low English language proficiency (80%; 95% CI, 52.8-93.5; P < 0.01). Non-Hispanic white, African American, and Asian American probands reported first-degree breast cancer family history with high accuracy, although sensitivity was lower for Hispanic white probands and those with low English language proficiency. Self-reported family history of breast cancer in first-degree relatives is highly accurate and can be used as a reliable standard when other validation methods are not available.

Socioeconomic inequalities in metastasis, recurrence, stage and grade of breast cancer: a hospital-based retrospective cohort study.

SummaryIntroductionThis study aims to estimate the Socio-Economic Status (SES) inequality on the metastasis, recurrence, stage and grade in Breast Cancer (BC).MethodsThis retrospective cohort study conducted on 411 BC patients in Arak, Iran. Asset-based questionnaire used to estimate the household SES. For calculate of SES inequality was used from Concentration Index (C). Moreover for investigate the association between recurrence and metastasis with other variables were used from multilevel logistic regression and analysis of variance were used to investigate the relationship between SES and other variables. The data were analyzed with Stata (v.13) software.ResultsResults of analysis of variance showed statistical significant relationship between SES with, insurance, surgery, grade, stage, recurrence and metastasis (p-value < 0.05). Moreover the Odds Ratio (OR) were significant of recurrence with age, academic level of education, supplementary insurance history of BC in first-degree relatives, stage and grade, also, metastasis with age of > 80 years, insurance, supplementary insurance, history of BC in first-degree relatives, chemotherapy, radiotherapy, stage and grade four. The total C index obtained 0.015 (0.002, 0.026), 0.011 (0.003, 0.031), – 0.014 (– 0.034, – 0.001) and – 0.042 (– 0.061, – 0.002) for metastasis, recurrence, stage and grade of BC respectively.ConclusionsOur results showed evidence of inequality in the metastasis, recurrence, stage and grade in BC patients.

First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis

BackgroundThe relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk.MethodsDatabases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach.ResultsEighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12–1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10–1.28) and sisters only (RR 1.71, 95% CI 1.43–2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74–4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04–1.34) with low-quality evidence.ConclusionsThis review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.

Use of dietary supplements in soy isoflavones and risk of breast cancer among women aged over 50 years: Results from the E3 N prospective cohort

Introduction Soy-based dietary supplements have been proposed as natural alternatives to menopausal hormone therapy, but their effect towards breast cancer risk is controversial and has little been evaluated. We investigated the association between the use of those supplements and breast cancer risk in a large prospective cohort of women aged over 50 years. Methods A total of 76,442 women from the E3 N cohort, born 1925–1950, were followed between 2000 and 2011 (11.2 years on average; 3608 incident breast cancers). Use of soy-based dietary supplements was assessed every 2–3 years. Hazard ratios (HRs) of breast cancer and their 95% confidence intervals (CI) associated with current, past, and never use of soy supplements were estimated using multivariable Cox models. Results HRs associated with current use of soy supplements were 0.92 (95% CI = 0.76 to 1.11) for breast cancer overall, 0.78 (95% CI = 0.60 to 0.99) for ER+ breast cancer and 2.01 (95% CI = 1.41 to 2.86) for ER- breast cancer, compared to never use. No association was observed for past use. We found effect modification by family history of breast cancer (P = 0.03) and menopausal status (P = 0.04): HRs for current use were 1.36 (95% CI = 0.95 to 1.93) among women with a family history of breast cancer in first-degree relatives, and 0.82 (95% CI = 0.65 to 1.02) among women with no such history; they were 1.06 (95% CI = 0.87 to 1.30) more than 5 years after menopause onset and 0.50 (95% CI = 0.31 to 0.81) in perimenopause or within 5 years after menopause. Conclusions We report opposite associations of soy-based dietary supplements with ER+ and ER− breast cancer risks. Our results suggest caution in using them in women with a family history of breast cancer. Whether their risk profile may be more favorable among premenopausal or recently postmenopausal women deserves further investigation.

Abstract 3242: Differences in stromal tumor-infiltrating lymphocytes in breast cancer from women of African and European ancestry after accounting for tumor characteristics

Abstract Background: Women of African ancestry (AA) have higher breast cancer mortality than other US racial/ethnic groups, attributed to a number of social and economic factors. However, breast tumors in AA women are more likely to present with higher grade and lacking estrogen receptor (ER) expression compared to those from women of European ancestry (EA), suggesting the importance of tumor factors in breast cancer disparities. Emerging evidence suggests that stromal tumor-infiltrating lymphocytes (TIL-str) have a role in immune response to therapy and prognosis of breast cancer. The objective of this study was to examine associations between risk factors for breast cancer and TIL-str, with consideration of tumor characteristics. Methods: We reviewed the hematoxylin and eosin slides from surgical or biopsy tumor blocks of invasive breast cancer from 1,385 cases (986 AA and 399 EA women, aged 20-75 years) in the Women's Circle of Health Study, a multicenter case-control study in New York and New Jersey. In-person interviews were conducted at diagnosis to obtain data on demographics, family histories, hormone use, and reproductive and menstrual histories. Anthropometric measurements were taken by trained staff. TIL-str were scored as 0%, 1%, and 10% to 100% in increments of 10%. Linear regressions were performed to estimate differences in TIL-str scores (β). Results: In univariate analysis, TIL-str was higher in tumors from AA than those from EA women overall (mean score = 21.5% vs. 12.5; P&amp;lt;0.001). TIL-str score was positively associated with higher grade, larger tumor size, and ER and progesterone receptor (PR) negativity in both AA and EA women (all P&amp;lt;0.05). In EA women, TIL-str score was also higher in more advanced than early stage tumors and human epidermal factor receptor 2 (HER2) positive than negative tumors (both P&amp;lt;0.05), but not in AA women. In multivariable analysis, AA compared to EA race was significantly associated with a higher TIL-str score (β = 5.7%, P&amp;lt;0.001), adjusting for age at diagnosis, body mass index, menopausal status, tumor grade, size, stage, and molecular subtypes defined by ER, PR, and HER2. There was no apparent association between TIL-str and history of breast cancer in first-degree relatives, history of benign breast disease, hormone use, reproductive factors, or body size. Conclusion: Self-reported African compared to European ancestry is independently associated with higher TIL-str scores in breast tumors. Our findings suggest that immune response may play a role in the differences in breast cancer biology and outcomes between AA and EA women. (Funding: The Breast Cancer Research Foundation; NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334) Citation Format: Ting-Yuan D. Cheng, Rochelle Payne Ondracek, Song Yao, Warren Davis, Angela Omilian, Mateusz Opyrchal, Elisa V. Bandera, Michael J. Higgins, Christine B. Ambrosone, Thaer Khoury. Differences in stromal tumor-infiltrating lymphocytes in breast cancer from women of African and European ancestry after accounting for tumor characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3242.

Abstract 2590: Development and validation of a breast cancer risk prediction model for black women: findings from the Nigerian breast cancer study

Abstract Background: Breast cancer (BC) risk prediction models, such as the Gail model, have been developed and widely used to identify women at higher risk of having breast cancer in developed countries. However, no model exists for Black women of sub-Saharan Africa (SSA). Because African women have different risk profiles, it is of public health importance to develop a Black women-specific model. Methods: A total of 1,880 hospital-based cases and 2,166 population-based controls from the Nigerian Breast Cancer Study (NBCS, 1998∼2015) were included in the analysis. Subjects were randomly divided into the training (2/3 of the data) and validation sets (1/3 of the data), and multivariate logistic regressions were used to derive the model. Risk factors were selected based on previous NBCS findings and literature review. Calibration and discrimination performances were assessed using the observed/expected ratio (O/E) and concordance statistic (C-index), respectively. Results: The final model included age, age at menarche, parity, duration of breast feeding, family history of BC in first degree relatives, height, body mass index, benign breast diseases, oral contraceptive use, and alcohol drinking. The model performed well in the validation set with an O/E of 1.01 (95% CI: 0.93∼1.09) and C-index of 0.694 (95% CI: 0.666∼0.722). The odds ratios for developing BC by percentiles of the predicted chance of cases, relative to women in the middle quintile, showed a monotonic increasing trend. Conclusion: In Nigeria, the most populous country in SSA with 175 million people, this study developed and validated a risk prediction model for BC that is specific to Black women. It can be used to identify individuals at high risk of BC for cancer prevention. Using the population incidence rates in Nigeria, an absolute risk prediction model will be further developed. Table 1Validation analyses in both training set and validation setPercentile of predicted chance being casesTraining set (n = 2699) OR (95%CI)Validation set (n = 1347) OR (95%CI)&amp;lt;5%0.18(0.10-0.30)0.24 (0.11-0.55)5%∼20%0.31(0.23-0.41)0.53(0.36-0.78)20%∼40%0.62(0.48-0.79)0.83(0.60-1.16)40%∼60%1.00(referent)1.00(referent)60%∼80%1.50(1.18-1.90)1.74(1.25-2.44)80%∼95%2.76(2.10-3.62)3.68(2.48-5.44)95%∼8.53(4.93-14.77)7.43(3.76-14.69)C-index0.724(0.705-0.742)0.694(0.666-0.722) Citation Format: Shengfeng Wang, Temidayo Ogundiran, Adeyinka Ademola, Oluwasola A. Olayiwola, Adewunmi Adeoye, Adenike Adeniji-Sofoluwe, Imran Morhason-Bello, Stella Odedina, Imaria Agwai, Clement Adebamowo, Millicent Obajimi, Oladosu Ojengbede, Olufunmilayo I. Olopade, Dezheng Huo. Development and validation of a breast cancer risk prediction model for black women: findings from the Nigerian breast cancer study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2590.

The transtheoretical model, health belief model, and breast cancer screening among Iranian women with a family history of breast cancer.

Background:Participation of Iranian women with a family history of breast cancer in breast cancer screening programs is low. This study evaluates the compliance of women having a family history of breast cancer with clinical breast exam (CBE) according to the stage of transtheoretical model (TTM) and health belief model (HBM).Materials and Methods:In this cross-sectional study, we used Persian version of champion's HBM scale to collect factors associated with TTM stages applied to screening from women over 20 years and older. The obtained data were analyzed by SPSS, using descriptive statistics, Chi-square test, independent t-test, and analysis of covariance.Results:Final sample size was 162 women. Thirty-three percent were in action/maintenance stage. Older women, family history of breast cancer in first-degree relatives, personal history of breast disease, insurance coverage, and a history of breast self-examination were associated with action/maintenance stage. Furthermore, women in action/maintenance stages had significantly fewer perceived barriers in terms of CBE in comparison to women in other stages (P < 0.05). There was no significant difference in other HBM subscales scores between various stages of CBE screening behavior (P > 0.05).Conclusion:The finding indicates that the rate of women in action/maintenance stage of CBE is low. Moreover, results show a strong association between perceived barriers and having a regular CBE. These clarify the necessity of promoting national target programs for breast cancer screening, which should be considered as the first preference for reducing CBE barriers.

Abstract B17: Family history of breast and ovarian cancer prevalence and its association with triple-negative subtype in Hispanic women

Abstract Background: A family history of breast cancer in a first-degree relative is an established risk factor for breast cancer; however, little is known about the profile of breast and ovarian family history in Hispanic/Latina women. Importance of this relates to recent reports showing a high prevalence of BRCA mutations in Hispanic/Latina women and a pattern of multiple recurrent mutations. In addition, less is known about the association of family history and tumor subtype in this growing ethnic group in the U.S. Methods: Study participants included breast cancer patients of Mexican descent enrolled in the Ella Binational Breast Cancer Study. We first assessed the self-reported breast and ovarian family history profile in 1,150 women. Second, we compared differences in family history of breast and ovarian cancer prevalence between triple negative breast cancer (TNBC) and non-TNBC in 914 patients with available tumor subtype data. Logistic regression was conducted to compare odds of TNBC to non-TNBC according to family history of breast and ovarian cancer. Results: Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively. A history of breast or ovarian cancer in first-degree relatives was reported in 14.9% of the women. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC compared to non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC was 1.93 (95% CI, 1.26–2.97) for women with first-degree relatives with breast or ovarian cancer. There was a suggestion of stronger associations between family history and TNBC among women diagnosed at age &amp;lt;50 compared to those &amp;gt;50 years for breast cancer history in first-degree (P-interaction=0.14) and first- or second-degree relatives (P-interaction=0.07). Conclusion: Findings suggest that familial cancers are associated with triple negative subtype, possibly related to the prevalence of BRCA mutations in Hispanic women, which are strongly associated with TNBC. Improvement in collection of family history through new tools and instruments targeting English- and Spanish-speaking Hispanic women should be a priority for future research. Identification of a strong family history can ultimately affect treatment plans, screening practices, and prevention options both for patients and their relatives. Citation Format: Maria Elena Martinez, Kristin Anderson, Patricia Thompson, Betsy C. Wertheim, Lorena Martin, Ian Komenaka, Melissa Bondy, Adrian Daneri-Navarro, Maria Mercedes Meza-Montenegro, Luis Enrique Gutierrez-Millan, Abenaa Brewster, Lisa Madlensky, Malaika Tobias, Loki Natarajan. Family history of breast and ovarian cancer prevalence and its association with triple-negative subtype in Hispanic women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B17.

Abstract 2747: Increasing age at first full-time pregnancy correlates to use of oral contraceptives before age 20 in women with a family history of breast cancer

Abstract Background Women with a family history of breast cancer (BC) in first-degree female relatives have an increased risk of BC. The aim of this study was to determine the BC risk associated with exposure to endogenous and exogenous hormones in familial BC compared with non-familial BC. Materials and methods A population-based prospective questionnaire-based cohort was initiated in 1990 in the South Swedish Health Care Region. Forty thousand healthy women between ages 25 to 65 years were randomly selected, out of which 29,520 answered the first questionnaire. Data was subsequently collected from several registries and a second questionnaire. Familial BC was defined as having first-degree relatives (mother, sisters, and/or daughters) diagnosed with BC. Known mutation carriers in BRCA-related genes (n = 13) were excluded from all analyses. To determine whether there are any differences between familial and non-familial BC risk according to hormonal exposures, Cox proportional hazard models were used. Hazard ratios (HR) were estimated with 95% confidence intervals (CI), and all models were adjusted for birthdate. Results At the end of follow-up (10/31/2013), 1,500 (5%) of the women were diagnosed with BC. Out of the 1,500 BC cases, 192 women (13%) had a family history of BC. Having a family history of BC in first-degree relatives was twice as prevalent among BC cases compared with women without BC diagnosis (OR 1.9 (CI 1.63-2.23)). When adjusting for age at menarche and ever-use of oral contraceptives (OC), an increased age at first full-time pregnancy was associated with an increased risk of BC, both for BC cases with familial BC and non-familial BC, HR 1.02 (CI 1.00-1.03) and HR 1.01 (CI 1.00-1.02), respectively. Adjusted for age at menarche and parity, an increased risk of BC was associated with use of OC before age 20 (HR 1.7 (CI 0.99-2.80)) for BC cases with familial BC compared with non-BC cases with familial BC. This was not observed in women with non-familial BC. Conclusion The main findings in this study were that older age at first full-time pregnancy has a larger impact on BC risk in women with familial BC than in women without, and that use of OC before age 20 increases the risk of BC in women with familial BC, not observed in women without. Well known familial and/or hormonal risk factors for BC were observed in our study, implying the validity of the cohort. Our results indicate similarities in risk of BC between women with, and without, familial BC regarding age at first full-term pregnancy. However, the impact seems to be larger in familial BC. If confirmed in other studies, our findings could be of interest for women with familial BC, especially regarding the increased risk when using OC during adolescence, where other alternatives are available. Citation Format: Annelie Augustinsson, Carolina Ellberg, Ulf Kristoffersson, Håkan Olsson. Increasing age at first full-time pregnancy correlates to use of oral contraceptives before age 20 in women with a family history of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2747. doi:10.1158/1538-7445.AM2015-2747

Abstract 2777: Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 in HRR pathway genes and risk of breast cancer in China

Abstract BACKGROUND: MiRNA-binding-site single nucleotide polymorphisms (SNPs) in homologous recombination repair (HRR) pathway genes may change DNA repair capacity and affect susceptibility to cancer. However, these SNPs associated with breast cancer (BC) are still unclear in Chinese women. METHODS: We performed a case-control study of 450 BC patients and 450 matched cancer-free controls in Chinese Han women. Five miRNA-binding-site SNPs in HRR pathway genes (MRE11A rs2155209, NBS1 rs2735383, RAD51 rs963917 and rs963918 and RAD52 rs7963551) were genotyped by the restriction fragment-length polymorphism (PCR-RFLP) method; a chi-square (χ2) test was used to compare the differences in the genotypic distribution between the BC cases and controls. The interactions of gene-gene and gene-reproduction factors were computed by logistic regression models. RESULTS: Gene-gene and gene-reproduction factors interaction analysis among HRR pathway genes showed significant effects on BC risk. the individuals with TC (OR: 1.87; 95% CI: 1.23-2.86) and TC+CC (OR: 1.86; 95% CI: 1.23-2.80) genotypes of rs2155209 in MRE11A showed increased risk to BC compared with TT genotype after adjustment for age, age at menarche and menopause, menopausal status, number of pregnancy and abortion, breast-feeding status, family history of BC in first-degree relatives. Compared with AA genotype, patients with AC, CC and AC+CC genotype of rs7963551 in RAD52 had a significantly lower risk for BC [OR (95%CI) as 0.67 (0.48, 0.87), 0.36 (0.24, 0.58) and 0.71 (0.59, 0.82), respectively]. Haplotypes of Crs963917Ars963918 decreased the risk of BC (OR: 0.53; 95%CI: 0.41-0.68), while the Trs963917Ars963918 and Trs963917Grs963918 haplotypes could increase the risk of BC (OR: 1.28; 95%CI: 1.05-1.57 and OR: 1.31; 95%CI: 1.09-1.62). Combined Effect of risk alleles showed that the five SNPs were associated with increased breast cancer risk in a dose-dependent manner (Ptrend = 0.003). The GC genotype of rs2735383, AG+GG genotype of rs963918 and AC+CC genotype of rs7963551 were associated with PR positive of BC patients. And among the stratified analysis, no heterogeneity was observed in any strata of the subgroups. CONCLUSION:These findings suggest that the miRNA-binding-site SNPs involved in HRR pathway genes may affect susceptibility of BC in Chinese women; moreover, the interactions of gene-gene and gene-reproduction factors play vital roles in the progression on BC. Further functional studies are needed to validate our results. Citation Format: Chunhua Song, Kaijuan Wang, Zhenzhen Wu, Ye Hua, Peng Wang, Yong Hong Zheng, Xiaoqin Cao, Songyuan Deng. Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 in HRR pathway genes and risk of breast cancer in China. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2777. doi:10.1158/1538-7445.AM2015-2777

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.