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The effect of parity and oral contraceptive (OC) use on breast cancer risk differs by cancer subtype as defined by histology. Family history of breast cancer impacts decisions regarding both parity and oral contraceptive use; it is unknown whether reproductive risk factors are related to uncommon histologies in women with and without a strong family history. Methods: Using population-based data from the Breast Cancer Family Registry, we conducted analyses using unordered polytomous regression to determine the role of family history in associations between parity, OC use, and breast cancer histologic subtype, among 3,260 cases and 2,997 controls. Histologic types examined included ductal and lobular as well as the uncommon histologies of mucinous, tubular, and medullary cancer. Results: Twenty-eight percent of cases and 9% of controls had a family history (defined as at least 1 first-degree relative with breast cancer). Cases with and without family history were similar in regards to OC use (75% and 73%, respectively were ever-users) and parity (2.08 children in cases with family history, 2.10 in cases without). In a multivariable model, when compared with controls, OC use was inversely associated with tumors of mucinous histology (OR ¼ 0.43, 95% CI 0.23-0.79 for use !5 years vs. never use). There was a stronger inverse association with OC use and the mucinous subtype among those without a family history (OR ¼ 0.27, 95% CI 0.13-0.57), and a nonsignificant positive association in those with family history (OR ¼ 2.19, 95% CI 0.40-11.84). High parity (!3 children) was positively associated with medullary histology (OR ¼ 2.62, 95% CI 1.16-5.91, compared with nulliparity); the association was stronger among women without a family history (OR ¼ 4.31, 95% CI 1.67-11.12), and was not significantly associated among those with a family history (OR ¼ 0.36, 95% CI 0.06-2.29). Parity was inversely associated with the mucinous type (OR ¼ 0.45, 95% CI 0.21-0.96, compared with nulliparity), and this effect remained stable in women with and without family history. Conclusion: This study suggests that selected reproductive risk factors may only be related to uncommon breast cancer histologies among women without a family history of breast cancer.

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