Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2

Background Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnanc y decreases the risk of early-onset hereditary breast cancer is unknown. Th ere is concern that pregnancy may increase breast-cancer risk in carriers o f BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnan cy is a risk factor for hereditary breast cancer. Methods We did a matched case-control study of breast cancer in women who c arry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who develope d breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or o ophorectomy, or who were diagnosed with ovarian cancer before the age at wh ich breast cancer was diagnosed in the matched case were excluded. Informat ion about pregnancies and pregnancy outcome was derived from a questionnair e completed by women in the course of genetic counselling. Findings A higher proportion of cases than controls had had a full term pre gnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). Th e mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differen ces in age at first birth or age at last birth between cases and controls. Interpretation Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carri ers who are nulliparous. Each pregnancy is associated with an increased can cer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.