High Risk For Hereditary Breast Cancer Research Articles

Isoflavone intake on the risk of overall breast cancer and molecular subtypes in women at high risk for hereditary breast cancer.

We investigated the association between isoflavone (ISF) intake and hereditary breast cancer (BC) risk, particularly by molecular subtype, in East-Asian BRCA1/2 mutation carriers and non-carriers at a high risk of hereditary breast cancer (i.e., family historyof BC (FHBC) and early-onset BC [EOBC, age < 40years]). The association between ISF intake and BC risk by molecular subtypes was assessed in 1709 participants (407 BRCA1/2 carriers, 585 FHBC non-carriers, 586 EOBC non-carriers, and 131 unaffected non-carriers) from the Korean Hereditary Breast Cancer Study using hazard ratios (HRs) and 95% confidence intervals (CIs) in weighted Cox regression models. Daily ISF intake was assessed using a validated food frequency questionnaire. We evaluated gene-environment interactions between BRCA1/2 mutation and ISF intake in 1604 BC cases by calculating the case-only odds ratios (CORs) and 95% CIs in logistic regression models. ISF intake was inversely associated with luminal A BC risk in BRCA2 mutation carriers and FHBC non-carriers (HR = 0.14, 95% CI = 0.04-0.50 for high intake [ISF intake ≥ 15.50mg/day]; HR = 0.27, 95% CI = 0.11-0.69 for high intake, respectively). We observed a reduced risk of triple negative BC (TNBC) in BRCA1 carriers and FHBC non-carriers (HR = 0.09, 95% CI = 0.02-0.40 for high intake; HR = 0.19, 95% CI = 0.05-0.69 for high intake, respectively). In the case-only design, an interaction between BRCA1 mutation carrier status and ISF intake emerged in TNBC patients (COR = 0.39, 95% CI = 0.16-0.95). This study suggests that ISF intake is inversely associated with BC risk in women at high risk of hereditary BC and that the effect could differ by molecular subtypes.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer.

PurposeWe evaluated the risk of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) and investigated the predictive factors for CBC and IBTR in breast cancer patients with BRCA mutations and non-carriers at high-risk of hereditary breast and ovarian cancer (HBOC).MethodsWe analyzed prospectively collected clinical data of patients with unilateral breast cancer who were at high-risk for HBOC and were tested for the BRCA mutation between 2003 and 2013.ResultsThe cohort comprised 540 patients with 45 BRCA1 carriers, 50 BRCA2 carriers, and 445 non-carriers. The median follow-up was 84.5 months. Overall, 61 patients (11.3%) developed CBC (24.4% for BRCA1 carriers, 20% for BRCA2 carriers, and 9% for non-carriers). The 10-year cumulative risk for CBC was 23.8% for BRCA1 carriers, 19.1% for BRCA2 carriers, and 9.8% for non-carriers (p = 0.174). Among the 277 patients who underwent breast-conserving surgery, 29 (10.5%) developed IBTR (9.1% for BRCA1 carriers, 16.7% for BRCA2 carriers, and 10.2% for non-carriers). The 10-year cumulative risk for IBTR for BRCA1 carriers, BRCA2 carriers, and non-carriers was 8.7%, 14.1%, and 20%, respectively (p = 0.577). BRCA1 (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.20–7.20; p = 0.019) and BRCA2 (HR, 2.88; 95% CI, 1.13–7.35; p = 0.027) mutations and negative estrogen receptor status (HR, 4.02; 95% CI, 1.60–10.08; p = 0.003) were the significant predictive factors for CBC, while tumor size ≥ 2 cm was predictive of IBTR (HR, 6.11; 95% CI, 2.03–18.33; p = 0.001).ConclusionWhile BRCA1/2 mutation carriers had a higher risk of developing CBC compared to non-carriers at high-risk of HBOC, the risk of IBTR was similarly high across breast cancer patients irrespective of the BRCA mutation. Further preventive strategies to reduce CBC and IBTR for all patients at high-risk of HBOC should be investigated.

Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer

BackgroundThe purpose of our study was to compare differences in the prognosis of breast cancer (BC) patients at high (H) risk or intermediate slightly (IS) increased risk based on family history and those without a family history of BC, and to evaluate whether ten-year overall survival can be considered a good indicator of BRCA1 gene mutation.MethodsWe classified 5923 breast cancer patients registered between 1988 and 2006 at the Department of Oncology and Haematology in Modena, Italy, into one of three different risk categories according to Modena criteria. One thousand eleven patients at H and IS increased risk were tested for BRCA1/2 mutations. The overall survival (OS) and disease free survival (DFS) were the study end-points.ResultsEighty BRCA1 carriers were identified. A statistically significantly better prognosis was observed for patients belonging to the H risk category with respect to women in the IS and sporadic groups (82% vs.75% vs.73%, respectively; p < 0.0001). Comparing only BRCA1 carriers with BRCA-negative and sporadic BC (77% vs.77% vs.73%, respectively; p < 0.001) an advantage in OS was seen.ConclusionsPatients belonging to a population with a high probability of being BRCA1 carriers had a better prognosis than those with sporadic BC. Considering these results, women who previously had BC and had survived ten years could be selected for BRCA1 analysis among family members at high risk of hereditary BC during genetic counselling. Since only 30% of patients with a high probability of having hereditary BC have BRCA1 mutations, selecting women with a long term survival among this population could increase the rate of positive analyses, avoiding the use of expensive tests.

Breast cancer susceptibility genes: Options for those carrying BRCA1 mutations

The discovery of the association between breast and ovarian cancer and the BRCA genes and the development of methods for genetic testing made it possible to screen women for genetic predisposition to develop hereditary breast cancer (HBC). Parallelly, prevention strategies, including clinical surgical and medical interventions become available in order to reduce cancer risk. In a meantime, we became aware of limitations of genetic testing from the aspect of BRCA gene penetrance, negative result interpretation etc. All of these, together with data that invasive prevention strategies such as prophylactic surgery demonstrate better results in risk reduction than regimens including self and clinical-examination, face BRCA mutation carriers with difficult choice for risk reduction options. Therefore, the patients at high risk of HBC can best make informed decisions when guided by a multidisciplinary genetic counseling team.