Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. 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 than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies

Family History of Breast, Ovarian and Endometrial Cancer and Risk of Breast Cancer

The relationship between family history of breast, ovarian and endometrial cancer and risk of breast cancer was analysed using data from a case-control study of breast cancer conducted in the greater Milan area, Northern Italy. The cases studied were 3415 women (median age 52 years, range 23-74) who had histdogically confirmed breast cancer diagnosed within the year precedmg the interview. The controls were 2916 women (median age 54 years; range 21-74] In hospital for a spectrum of acute illnesses excluding gynaecological, hormonal or neoplastic conditions. A total of 375 cases (11.0%) and 128 controls (4.4%) reported a history of breast cancer in first degree relatives. Compared with women with no family history of breast cancer, the RR was 2.7 (95% confidence Interval [CI] : 2.2-3.3) in those with one first degree relative affected and 2.8 (95% CI : 1.3-5.7) in those with two or more affected relatives. In comparison with women without family history of ovarlan cancer the RR of breast cancer was 1.4 (95% CI : 0.9-2.3) for those reporting one or more first degree relatives with ovarian cancer. However, the multivariate estimate for family history of ovarian cancer, including a term for familial breast cancer, decreased to 0.8 (95% CI : 0.5-1.4). The risk of breast cancer was similar in women reporting a family history of breast cancer (RR=2.2) and in those reporting a family history of both breast and ovarian cancer (RR=2.51, in cornparkon with women reporting no family history of breast and/or ovarian cancer. When tlia relation with family history of breast cancer was analysed in strata of women with and without family history of ovarian cancer, no difference was found in the RR estimates: the RR for family history of breast cancer was 2.8 in women with family history of ovarian cancer and 2.7 in those without history of ovarian cancer. No relation was found between history of endometrial cancer in first degree relatives and risk of breast cance

BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on similar to 4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.Peer reviewe

Population-based estimates of the relation between breast cancer risk, tumor subtype, and family history.

OBJECTIVE: Many studies that have estimated the breast cancer risk attributable to family history have been based on data collected within family units. Use of this study design has likely overestimated risks for the general population. We provide population-based estimates of breast cancer risk and different tumor subtypes in relation to the degree, number, and age at diagnosis of affected relatives. METHODS: Cox Proportional Hazards to calculate risks (hazard ratios; 95% confidence interval) of breast cancer and tumor subtypes for women with a family history of breast cancer relative to women without a family history among a cohort of 75,189 women age >or=40 years of whom 1,087 were diagnosed with breast cancer from June 1, 2001-December 31, 2005 (median follow-up 3.16 years). RESULTS: Breast cancer risk was highest for women with a first-degree family history (1.54; 1.34-1.77); and did not differ substantially by the affected relative's age at diagnosis or by number of affected first-degree relatives. A second-degree family history only was not associated with a significantly increased breast cancer risk (1.15; 0.98-1.35). There was a suggestion that a positive family history was associated with risk of triple positive (Estrogen+/Progesterone+/HER2+) and HER2-overexpressing tumors. CONCLUSIONS: While a family history of breast cancer in first-degree relatives is an important risk factor for breast cancer, gathering information such as the age at diagnosis of affected relatives or information on second-degree relative history may be unnecessary in assessing personal breast cancer risk among women age >or=40 years

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Set-up of a population-based familial breast cancer registry in Geneva, Switzerland: validation of first results

Background: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. Patients and methods: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (κ) were calculated. Results: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and κ of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and κ were 67%, 99%, and 0.66, respectively. Conclusions: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verificatio

Self-Reported Chemicals Exposure, Beliefs About Disease Causation, and Risk of Breast Cancer in the Cape Cod Breast Cancer and Environment Study: A Case-Control Study

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.Massachusetts Legislature; Massachusetts Department of Public Health; Susan S. Bailis Breast Cancer Research Fund at Silent Spring Institute; United States Centers for Disease Control and Prevention (R01 DP000218-01, 1H75EH000377-01

The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study

Background: The potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear.Methods: A large population-based case-control study on breast cancer in postmenopausal women in Germany recruited 2002-2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015.Results: A first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p &lt; 0.001). Patients with a first degree family history of breast cancer were more likely to have had &gt;10 mammograms (MG) (42.7% vs. 24.9%, p &lt; 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p &lt; 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p &lt; 0.001) and a higher number of MG (&gt;= 10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p &lt; 0.001) and imaging-assisted tumor detection (HR 0.66, p &lt; 0.001) were associated with better overall survival but not with a positive family history.Discussion: Patients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history. (C) 2020 The Authors. Published by Elsevier Ltd.</p

Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study

Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrolment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73–1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (ptrend=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47–1.19, ptrend=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer