Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer

Context Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a fam ilial predisposition to breast cancer is less clear. Objective To determine whether the association between OC use and risk of b reast cancer is influenced by family history of the disease. Design and Setting Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the Univer sity of Minnesota Hospital. Follow-up data on families were collected by te lephone interview between 1991 and 1996. Participants A total of 394 sisters and daughters of the probands, 3002 gra nd daughters and nieces, and 2754 women who married into the families. Main Outcome Measure Relative risk (RR) of breast cancer associated with hi story of OC use by relationship to proband. Results After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sister s and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6 -6.7), but not among granddaughters and nieces of the probands (RR, 1.2, 95 % CI, 0.8-2.0) or among marry-ins (RR, 1.2, 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The el evated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations wer e likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the st atistical power to detect risk among women with a first-degree relative wit h breast cancer and OC use after 1975. Conclusions These results suggest that women who have ever used earlier for mulations of OCs and who also have a first-degree relative with breast canc er may be at particularly high risk for breast cancer. Further studies of w omen with a strong family history who have used more recent lower-dosage fo rmulations of OCs are needed to determine how women with a familial predisp osition to breast cancer should be advised regarding OC use today.