INTRODUCTION: Benign breast disease (BBD) describes a heterogeneous group of premalignant lesions associated with an increased risk of breast cancer development, especially in those with proliferative BBD with atypia. Whether BBD is associated with higher all-cause mortality is unsettled. Therefore, we examined the association between incident BBD, BBD histotypes and all-cause and breast cancer-specific mortality among WHI participants.

METHODS: Included were 68,132 postmenopausal women enrolled in the WHI clinical trials from 1993-1998 at 40 US clinical centres, followed up through March 2019. In these trials, serial mammography was mandated and compliance was high. Cases were participants in the BBD ancillary study (AS)130 with incident BBD confirmed by central pathology review. The comparison group included all other clinical trial participants (intervention and control groups). Cox proportional hazard regression models, stratified by baseline age, clinical trial arms and WHI extension study participation, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality in association with BBD. Analyses were adjusted for age, race/ethnicity, education, income, smoking, BMI, waist circumference, energy intake, alcohol, physical activity, reproductive factors, family history of breast cancer, Gail model score, history of menopausal hormone therapy (MHT) use and history of comorbidities.

RESULTS: Compared to women without incident BBD (n=43,439), women with incident BBD (n=3,467) were younger (p<0.001), more likely to have a higher education level (p=0.003), higher income (p<0.001), lower BMI (p=0.003) and waist circumference (p=0.002), a Gail risk score of >1.75 (p<0.001), a family history of breast cancer (p<0.001) and used MHT (p<0.001). There were 737 deaths among the BBD case group and 8,949 deaths among the non-case group. In adjusted analyses, no association was observed between incident BBD and all-cause mortality (HR:0.92, 95%CI: 0.83, 1.01). In adjusted analyses stratified by BBD, compared to women without BBD, no association for all-cause mortality was observed for women with non-proliferative BBD (n=374; HR:0.96; 95%CI: 0.84, 1.09), proliferative BBD without atypia (n=309; HR:0.91, 95%CI: 0.79, 1.05) or proliferative BBD with atypia (n=54; HR:0.72, 95% CI: 0.51, 1.03). In secondary analyses, compared to women without incident BBD, women with incident BBD had a statistically significantly higher breast cancer-specific mortality both for BBD overall and for each BBD histotype.

CONCLUSIONS: In postmenopausal women, while a BBD diagnosis was associated with a statistically significant higher risk of breast cancer-specific mortality, irrespective of histotype, a BBD diagnosis was not associated with higher all-cause mortality.

Citation Format: Maeve Mullooly, Kathy Pan, Sowmya Vasan, Gretchen L. Gierach, Dorothy S. Lane, Aladdin H. Shadyab, Juhua Luo, Lihong Qi, Kathleen E. Bennett, Thomas E. Rohan, Rowan Chlebowski. Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 789.