Breast cancer is a heterogeneous disease; risk factors may differ for histologically‐defined subgroups. Because most breast cancers are of ductal or lobular histology, previous studies have been limited in their ability to evaluate risk factors in rarer histologies, such as medullary, mucinous, and tubular, due to small sample sizes. We evaluated risk factors for histologically‐defined breast cancer subgroups (ductal, lobular, tubular, medullary, or mucinous) using population‐based data from the Breast Cancer Family Registry. Data were available for 3260 incident breast cancer cases (including 92 cases of medullary, 90 cases of mucinous, and 86 cases of tubular histology) and 2997 unrelated controls. Several reproductive factors were associated with the risk of mucinous breast cancer, whereas cigarette smoking and body mass index (BMI) were associated with the risk of medullary breast cancer. For the mucinous subtype, we observed positive associations with nulliparity (OR=2.54, 95%CI 1.17–5.50) and age at first birth (OR=1.08, 95%CI=1.02–1.14, for each additional year of age), and an inverse association with age at menarche (≥13 vs. ≤11) (OR=0.52, 95%CI 0.29–0.94). These reproductive factors were not associated with other histologic subtypes. Mucinous cases were less likely than controls to have used oral contraceptives (OC use ≤ 5 years: OR=0.50, 95%CI 0.28–0.92; OC use > 5 years, OR=0.45, 95%CI 0.24–0.84), and these findings did not differ by menopausal status. Oral contraceptive use was also inversely associated with tubular histology among premenopausal women only (OC use > 5 years, OR=0.35, 95%CI 0.14–0.87), but was not associated with other histologic subtypes when compared with controls. Medullary histology was inversely associated with smoking status (former smoker vs. never smoker, OR=0.30, 95%CI 0.14–0.62), and positively associated with BMI (OR=1.05, 95%CI 1.01–1.09, for each one‐unit increase in BMI). Other known breast cancer risk factors, such as hormone‐replacement therapy (HRT), breastfeeding history, and alcohol use, were not associated with the any of the rarer subtypes. Family history of breast cancer was associated with increased risk of all histologic subtypes. If replicated, these findings suggest different patterns for selected breast cancer risk factors, such as parity, oral contraceptive use, and smoking, by tumor histology.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B132.