Family history, age, and risk of breast cancer: prospective data from the Nurses' Health Study

Women may have a higher risk of developing breast cancer if their mother or sister have had the disease. The increase in risk associated with a family history of breast cancer may be smaller than previously thought. Among 117,988 women between 30 and 55 years old in 1976 who were followed until 1988, 2,389 developed invasive breast cancer. The highest risk of breast cancer occurred among women whose mother was diagnosed with breast cancer before the age of 40. These women had twice the risk of developing breast cancer as women with no maternal history of breast cancer. The risk of breast cancer was also higher among women whose mother was diagnosed with breast cancer after the age of 70 or whose sister had breast cancer. However, only 2.5% of the women diagnosed with breast cancer had a family history of the disease.
Objective.-To examine the risk of breast cancer as influenced by a maternal history of breast cancer, the mother's age of diagnosis, or a sister's history of breast cancer. Design.-Prospective cohort study with biennial follow-up. Setting/Participants.-117 988 women in the Nurses' Health Study aged 30 to 55 years in 1976, followed up through 1988 (1.3 million person-years of follow-up). Results.-We identified 2389 incident cases of invasive breast cancer. Compared with women without a maternal history of breast cancer, the age-adjusted relative risk (RR) of breast cancer was highest among women whose mother was diagnosed before the age of 40 years (RR, 2.1 [95% confidence interval, 1.6 to 2.8]). The RR decreased with advancing maternal age at time of diagnosis to 1.5 (95% confidence interval, 1.1 to 2.2) for maternal diagnosis after the age of 70 years. Having a sister with a history of breast cancer also was related to increased risk; for women with one sister with breast cancer compared with those with one sister without such a history, the age-adjusted RR was 2.3 (95% confidence interval, 1.6 to 3.4). Women whose mother and sister both had a history of breast cancer had an RR of 2.5 (95% confidence interval, 1.5 to 4.2) compared with those without a family history. These associations did not differ appreciably when stratified by age; menopausal status; history of benign breast disease; body mass index; age at menarche; or parity or age at first birth of the women at risk. The results remained unchanged when we controlled for these risk factors in multivariate models. despite slightly greater mammography surveillance and earlier detection of tumors among women with a family history of breast cancer, detection bias is unlike to account for more than a small part of the observed association. Conclusions.--Risk of breast cancer is approximately doubled among women whose mother had breast cancer diagnosed before the age of 40 years or who have a sister with breast cancer, and remains elevated even for those whose mothers were diagnosed with breast cancer at the age of 70 years or older. However, the risk associated with a mother or sister history of breast cancer is smaller than suggested by earlier retrospective studies. Overall, within this population of middle-aged women, only 2.5% of breast cancer cases are attributable to a positive family history. (JAMA. 1993;270:338-343)