Progression From Benign Breast Disease To Cancer In Women With A Family History Of Breast Cancer

Abstract Background: In the general population, benign breast disease (BBD) is an established risk factor for breast cancer, with increased risks ranging from 20 to 50% for atypical proliferative subtypes. There is limited data on the incidence of atypical hyperplasia (AH) and its association with breast cancer risk specifically among women with a strong family history (FH). Methods: In an ongoing, prospective cohort of women with a FH of breast cancer and/or a BRCA1/2 mutation who attend the Breast and Ovarian Surveillance Service (BOSS) at Johns Hopkins (N=1,132), we identified 259 pathology confirmed incident BBD cases diagnosed between 1959 to 2010. Slides were obtained for re-review and evaluation of specific histologic features. Cox proportional hazards models were used to estimate the risk of breast cancer relative to BBD subtype. Results: Of the incident BBD diagnoses, 61.4% were non-proliferative, 26.3% were proliferative without atypia, and 12.4% were AH. AH cases were diagnosed at an older age (p-value=0.04) and were less likely to have a strong FH (p-value=0.01) as compared to non-atypical subtypes. Sixty-one BBD cases progressed to cancer and the median time to diagnosis was significantly shorter for cases of AH (4.2 years) than for non-proliferative disease (8.8 years) (p<0.01). Women with AH were 2.36 (95% confidence interval (CI): 1.15, 4.87) times more likely to develop in-situ or invasive breast cancer compared to non-proliferative cases, adjusting for age and year of incident BBD. In models additionally adjusting for BRCA1/2 mutation status and degree of FH, women with AH had a 4.5-fold (95% CI: 2.16, 9.53) increased risk of breast cancer. BBD subtype and degree of FH were found to be independent risk factors for breast cancer. Prophylactic mastectomy and tamoxifen use post BBD diagnosis did not differ by BBD subtype or the total number of BBD diagnoses. Conclusion: Given the high incidence of AH in this cohort and the increased risk of breast cancer associated with this subtype, AH may be a viable target for preventative strategies in women with a FH of breast cancer. Further, AH does not seem to track with a stronger FH, suggesting two different breast cancer pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3568. doi:1538-7445.AM2012-3568