Effect of Reproductive Factors and Oral Contraceptives on Breast Cancer Risk inBRCA1/2Mutation Carriers and Noncarriers: Results from a Population-Based Study

Abstract

Background: Multiparity and breast-feeding reduce breast cancer risk, whereas oral contraceptive use may slightly increase breast cancer risk in the general population. However, the effects of these factors in BRCA1 and BRCA2 mutation carriers are less clear. Methods: Case patients were 1,469 women from Los Angeles County ages 20 to 49 years with newly diagnosed breast cancer. Control subjects were 444 women without breast cancer, individually matched to a subset of cases on race, age, and neighborhood. BRCA1/2 genes were sequenced in the cases, and odds ratios of breast cancer associated with various reproductive and hormonal factors in BRCA1/2 mutation carriers and noncarriers were estimated using multivariable logistic regression. Results: Ninety-four women had a deleterious BRCA1 or BRCA2 mutation. Number of full-term pregnancies was inversely associated with breast cancer risk

A Multicenter Matched Case Control Study of Breast Cancer Risk Factors among Women in Karachi, Pakistan

“…Our study showing the protective effect of parity is consistent with similar previous findings (Yuan et al, 1988;Egan et al, 1998). Several mechanisms have been proposed to explain the protective effect of pregnancy in the general population: decreased levels of estrogen and progesterone, increased levels of sex hormone-binding globulin, and pregnancy-induced differentiation of breast tissue (Lee et al, 2008).…”

Survival Analysis of Cancer Risk Reduction Strategies for BRCA1/2 Mutation Carriers

“…Among BRCA1 mutation carriers who choose no intervention, the likelihood of death from breast versus ovarian cancer is similar (41% v 36%, conditional on death by age 70; 26 Haile et al, 27 Jernströ m et al, 28 Lee et al, 29 McGuire et al, 30 McLaughlin et al, 31 Milne et al, 32 Modan et al, 33 Narod We assumed that the reduction in the probability of developing breast cancer after PM was 0.95 (95% reduction) per tumor; given the high risk of multiple primary tumors in BRCA1/2 mutation carriers, the overall reduction in probability of developing breast cancer after PM was 0.9 (90% reduction).…”

“…For sensitivity analysis, we assumed that women used oral contraceptive pills for at least 5 years: for the lower bound, this use was assumed to convey an HR of 0.5 for ovarian cancer with no change in the risk of breast cancer, and for the upper bound, this use was assumed to convey an HR of 0.5 for ovarian cancer with an HR of 1.5 for breast cancer. [26][27][28][29][30][31][32][33][34][35][36] HRs for death as a result of cardiovascular disease, hip fracture, and dementia, respectively, after PO is performed at age 40.…”

Exogenous sex hormones and risk of breast cancer

“…Exogenous estrogen does not seem to increase the risk of breast cancer by a positive family history of breast cancer, but OC use may increase risk to a greater extent in carriers of BRCA ½ mutations than in the general population [5], though this point of view was not confirmed in a latter study by Lee et al [6].…”

“…There are no reassuring data from two large studies that OCs do not increase breast cancer risk later in life [6,7]. Key findings included no breast cancer risk among current (OR, 1.0; 95% CI, 0.8-1.3) or former (OR, 0.9; 95% CI, 0.8-1.0) OC users and no risk associated with the duration of use or dose of estrogen.…”