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Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high risk
Oncotarget Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high risk 2017.10.31.
Oncotarget. 2017 Nov 24; 8(60): 102110–102118. 논문 보기
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.

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