Abstract

Abstract Background: Benign breast disease (BBD) is a term that encompasses a heterogeneous group of lesions with different levels of subsequent breast cancer risk. Large, epidemiologic follow-up studies have consistently shown that proliferative lesions without atypia are associated with a 1.5-2-fold increase in risk whereas atypical hyperplasias are associated with a 4-5-fold increase in risk. However, these data were derived primarily from populations of women who, for the most part, were biopsied before the widespread use of screening mammography and in whom these lesions were incidental findings. Whether or not similar levels of subsequent breast cancer risk are found when these lesions are detected in mammographically screened populations has not been previously investigated. Methods: To address this issue, we performed a nested case-control study within the Nurses’ Health Study (NHS) and NHSII BBD cohorts, including 488 women who had biopsy-proven BBD and on average 9 years later developed breast cancer (cases) and 1,908 women who had biopsy-proven BBD and did not develop breast cancer (controls). We performed logistic regression, adjusting for matching factors and potential confounders, to estimate odds ratios (OR) and 95% confidence intervals (CI) for developing subsequent breast cancer by BBD subtype. We stratified the analyses by the calendar time of BBD diagnosis (pre- vs. post-mammographic era [before vs. after 1985]) and the method of BBD detection (mammogram vs. self-exam/physician’s exam). Interaction tests were performed using the Wald test for product terms. Results: During the pre-mammographic era, proliferative lesions without atypia were associated with a 1.78-fold higher risk of breast cancer (95% CI=1.31-2.42) and atypical hyperplasia was associated with a 4.61-fold higher risk (95% CI=3.05-6.97) compared with nonproliferative lesions. The risk association was similar but slightly weaker during the post-mammographic era (proliferative lesions without atypia vs. nonproliferative: OR=1.14, 95% CI=0.74-1.76; atypical hyperplasia vs. nonproliferative: OR=3.54, 95% CI=2.14-5.88). When the analysis was stratified by the method of BBD detection, the risk association was similar but slightly attenuated in the stratum of BBDs found on self-exam or physician’s exam (atypical hyperplasia vs. nonproliferative: OR=4.16, 95% CI=2.81-6.16; proliferative without atypia vs nonproliferative: OR=1.54, 95% CI= 1.15-2.07) than in the stratum of BBDs found on mammography (atypical hyperplasia vs. nonproliferative: OR=5.54, 95% CI=2.57-12.0; proliferative without atypia vs nonproliferative: OR=1.15, 95% CI=0.80-3.31). The interaction by calendar time of BBD diagnosis and the method of BBD detection was not statistically significant (p-interaction=0.51 when stratified by pre- (before 1985) vs. post-mammography era (since 1985) and p-interaction=0.09 when stratified by the method of benign breast disease detection). Conclusions: Our data suggest that the risk associated with BBD subtypes initially reported from women biopsied in the pre-mammographic era remain valid for BBD detected after the widespread use of screening mammography was established. Citation Format: Francisco Beca, Hannah Oh, Laura C Collins, Rulla M Tamimi, Stuart J Schnitt. The impact of mammographic screening on the subsequent breast cancer risk associated with biopsy-proven benign breast disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-05.

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