Effect of lifestyle and reproductive factors on the onset of breast cancer in female BRCA 1 and 2 mutation carriers.
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ABSTRACT:
SUBMITTER: Rieder V
PROVIDER: S-EPMC4799878 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged ≤40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95% confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95%CI=2.03-6.00) and 3.30-fold in non-carriers with FH (95%CI=1.73-6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95% CI=0.09-0.83 for two parity; and HR=0.23, 95%CI=0.05-1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95%CI=2.56-8.51 for >3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95%CI=1.65-9.67; HR=7.69, 95%CI=1.96-25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity<0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, non-carriers with FH, and early-onset BC non-carriers.
| S-EPMC5731939 | biostudies-literature
Project description:IntroductionWomen who inherit a pathogenic mutation in Breast Cancer Susceptibility Genes 1 or 2 (BRCA1 or BRCA2) are at substantially higher risk of developing breast and ovarian cancer than the average woman. Several cancer risk management strategies exist to address this increased risk. Decisions about which risk management strategies to choose are complex, personal and multifactorial for these women. This scoping review will map evidence relevant to cancer risk management decision making in BRCA mutation carriers without a personal history of cancer. The objective is to identify and describe the features of patient decision aids that have been developed for BRCA mutation carriers. This information may be beneficial for designing new decision aids or adapting existing decision aids to support decision making in this population.Methods and analysisThis scoping review will be conducted according to the Joanna Briggs Institute's scoping review methodological framework. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will be used for guidance. Studies on decision aids for women with a BRCA mutation who are unaffected by breast or ovarian cancer will be considered for inclusion. Five electronic databases will be searched (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science) with no restrictions applied for language or publication date. Studies for inclusion will be selected independently by two review authors. Data will be extracted using a predefined data extraction form. Findings will be presented in tabular form. A narrative description of the evidence will complement the tabulated results.Ethics and disseminationEthical approval for conducting this scoping review is not required as this study will involve secondary analysis of existing literature. Findings will be published in a peer-reviewed journal and presented at relevant conferences.
| S-EPMC8276307 | biostudies-literature
Project description:PurposeGermline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer.MethodsWe retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014.ResultsAmong the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014).ConclusionOur results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.
| S-EPMC5620443 | biostudies-literature
Project description:BRCA1/2-mutation carriers are at high risk of breast cancer (BC) and ovarian cancer. Physical inactivity, overweight (body mass index ?25, BMI), smoking, and alcohol consumption are jointly responsible for about 1 in 4 postmenopausal BC cases in the general population. Limited evidence suggests physical activity also increases BC risk in BRCA1/2-mutation carriers. Women who have children often reduce physical activity and have weight gain, which increases BC risk. We assessed aforementioned lifestyle factors in a cohort of 268 BRCA1/2-mutation carriers around childbearing age (born between 1968 and 1983, median age 33 years, range 21-44). Furthermore, we evaluated the effect of having children on physical inactivity and overweight. Carriers were asked about lifestyle 4-6 weeks after genetic diagnosis at the Familial Cancer Clinic Nijmegen. Physical inactivity was defined as sports activity fewer than once a week. Carriers were categorized according to the age of their youngest child (no children, age 0-3 years and ?4 years). In total, 48% of carriers were physically inactive, 41% were overweight, 27% smoked, and 70% consumed alcohol (3% ?8 beverages/week). Physical inactivity was 4-5 times more likely in carriers with children. Overweight was not associated with having children. Carriers with children are a subgroup that may specifically benefit from lifestyle support to reduce BC risk.
| S-EPMC5502067 | biostudies-other
Project description:BRCA1 and BRCA2 mutation carriers with breast cancer have a high risk of ipsilateral breast cancer tumor recurrence (IBTR) and a high lifetime risk of contralateral breast cancer (CBC). The IBTR risk is significantly higher in women who elect breast conservation. Oophorectomy has a protective effect for both ipsilateral breast tumor recurrence and CBC. Patients with younger age of breast cancer onset have a significantly greater risk of CBC. Given the higher risk of IBTR and CBC, when indicated, patients with breast cancer should undergo genetic counseling early in their treatment course to assist them in their surgical decision-making. Knowledge of expected outcomes for BRCA1/2 mutation carriers following breast cancer treatment can help appropriately council patients and personalize cancer therapy.
| S-EPMC3938200 | biostudies-literature
Project description:INTRODUCTION: BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk of breast cancer in mutation carriers, but the effects of spontaneous and therapeutic abortions on the risk of hereditary breast cancer risk have not been well studied to date. METHODS: In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer. RESULTS: There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio = 0.36; 95% confidence interval 0.16-0.83; p = 0.02). CONCLUSION: Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers.
| S-EPMC1557713 | biostudies-literature
Project description:In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.
| S-EPMC8586340 | biostudies-literature
Project description:Identification of BRCA mutations in breast cancer (BC) patients influences treatment and survival and may be of importance for their relatives. Testing is often restricted to women fulfilling high-risk criteria. However, there is limited knowledge of the sensitivity of such a strategy, and of the clinical aspects of BC caused by BRCA mutations in less selected BC cohorts. The aim of this report was to address these issues by evaluating the results of BRCA testing of BC patients in South-Eastern Norway.1371 newly diagnosed BC patients were tested with sequencing and Multi Ligation Probe Amplification (MLPA). Prevalence of mutations was calculated, and BC characteristics among carriers and non-carriers compared. Sensitivity and specificity of common guidelines for BRCA testing to identify carriers was analyzed. Number of identified female mutation positive relatives was evaluated.A pathogenic BRCA mutation was identified in 3.1%. Carriers differed from non-carriers in terms of age at diagnosis, family history, grade, ER/PR-status, triple negativity (TNBC) and Ki67, but not in HER2 and TNM status. One mutation positive female relative was identified per mutation positive BC patient. Using age of onset below 40 or TNBC as criteria for testing identified 32-34% of carriers. Common guidelines for testing identified 45-90%, and testing all below 60 years identified 90%. Thirty-seven percent of carriers had a family history of cancer that would have qualified for predictive BRCA testing. A Variant of Uncertain Significance (VUS) was identified in 4.9%.Mutation positive BC patients differed as a group from mutation negative. However, the commonly used guidelines for testing were insufficient to detect all mutation carriers in the BC cohort. Thirty-seven percent had a family history of cancer that would have qualified for predictive testing before they were diagnosed with BC. Based on our combined observations, we suggest it is time to discuss whether all BC patients should be offered BRCA testing, both to optimize treatment and improve survival for these women, but also to enable identification of healthy mutation carriers within their families. Health services need to be aware of referral possibility for healthy women with cancer in their family.
| S-EPMC5480128 | biostudies-literature
Project description:BackgroundBreast cancer (BC) is very uncommon in young women (YW) and it is unclear whether a BRCA mutation has prognostic implications. Our aim was to evaluate the characteristics of YW with BC by comparing the long-term oncological results between BRCA-mutation carriers and non-carriers.MethodsWe retrospectively reviewed all the consecutive YW (aged 18-40 years) diagnosed with BC. Endpoints were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS).Results63 YW with a BRCA mutation were compared with 339 YW without BRCA mutation. BRCA-mutation carriers were younger (60.3% versus 34.8% if age ≤ 35 years, p = 0.001) and presented with more aggressive tumors (66.7% versus 40.7% if G3, p = 0.001; 57.2% versus 12.4% if biological subtype triple-negative, p = 0.001; 73.0% versus 39.2% if Ki67 ≥ 25%, p = 0.001). Non-carriers presented significantly better DFS, DDFS, and OS compared with BRCA-mutation carriers. Neoadjuvant chemotherapy was found to be an independent protective factor for OS in BRCA-mutation carriers.ConclusionsBC is more likely to present at a younger age (≤ 35 years) and with more aggressive characteristics (G3, triple-negative, Ki67 ≥ 25%) in YW with BRCA mutation compared with their non-mutated counterparts. Young BRCA-mutation carriers showed a poorer prognosis in terms of recurrence and survival compared with non-carriers. The implementation of neoadjuvant chemotherapy may improve survival in YW with BC and BRCA mutation.
| S-EPMC10452863 | biostudies-literature
Project description:BackgroundRetrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer.MethodsWe did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing.FindingsBetween Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0-9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5-98·4] vs 96·6% [95·8-97·3]; at 5 years: 83·8% [79·3-87·5] vs 85·0% [83·5-86·4]; at 10 years: 73·4% [67·4-78·5] vs 70·1% [67·7-72·3]; hazard ratio [HR] 0·96 [95% CI 0·76-1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89-97] vs 91% [88-94]; HR 0·59 [95% CI 0·35-0·99]; p=0·047) but not 5 years (81% [73-87] vs 74% [70-78]; HR 1·13 [0·70-1·84]; p=0·62) or 10 years (72% [62-80] vs 69% [63-74]; HR 2·12 [0·82-5·49]; p= 0·12).InterpretationPatients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences.FundingCancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.
| S-EPMC5805863 | biostudies-literature