Effect of Family History, Body-Fat Distribution, and Reproductive Factors on the Risk of Postmenopausal Breast Cancer

BACKGROUND: A family history of breast cancer reflects shared cultural factors, genetic predisposition, or both. There is evidence that the estimated risk associated with a family history of breast cancer increases multiplicatively in combination with other risk factors. We examined the combined effect of family history and anthropometric and reproductive factors on the risk of breast cancer in postmenopausal women. METHODS: Using data from a prospective cohort study, we studied 37,105 women 55 to 69 years of age to determine whether known risk factors for breast cancer are modified by a reported family history at the time of entry into the study. RESULTS: During the first 4 years of follow-up, 493 new breast cancers were diagnosed. The association of the waist-to-hip ratio (the circumference of the waist divided by that of the hips) with the risk of breast cancer was limited predominantly to women with a family history of breast cancer; the age-adjusted relative risk of breast cancer for the women above the fourth quintile for waist-to-hip ratio as compared with those below the first quintile was 3.2 in women with a family history of breast cancer and 1.2 for women without such a family history. An interaction was observed between a family history of breast cancer and the number of live-born children; the protective effect of higher parity was observed primarily among women with a family history of breast cancer. Similarly, the age-adjusted relative risk of breast cancer associated with a late age at first pregnancy (i.e., greater than or equal to 30 years) was 5.8 for women with a family history of breast cancer and 2.0 for women without such a family history. CONCLUSIONS: The increase in the risk of breast cancer associated with a high waist-to-hip ratio, low parity, or greater age at first pregnancy is more pronounced among women with a family history of breast cancer. These findings suggest etiologic differences between familial breast cancer and the sporadic form.