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

PURPOSE 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 history of BC (FHBC) and early-onset BC [EOBC, age < 40 years]). METHODS 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. RESULTS 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 ≥ 15.50 mg/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). CONCLUSIONS 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.