Advancing Evidence of the Associations between specific Benign Breast Diagnoses and Future Breast Cancer Risk

Benign breast disease (BBD) increases breast cancer risk; however, associations between specific BBD diagnoses and breast cancer risk are insufficiently studied.

We analyzed 131,075 benign breast biopsy episodes from 1994-2022 identified from eight Breast Cancer Surveillance Consortium registries. Pathological diagnoses were classified into 38 BBDs within 4 categories. For comparison, women with no prior breast biopsy and a negative screening mammogram (N=1,599,694) were identified. Associations of BBDs with invasive breast carcinoma and ductal carcinoma in situ (DCIS) were estimated using Fine-Gray competing risk models.

Over a median follow-up of 7.5 years, 35,251 invasive breast cancers and 9,743 DCIS cases occurred. Lobular carcinoma in situ was associated with a 5.61-fold (95% confidence interval [CI]: 4.10-7.68) increased risk of invasive carcinoma and an 8.82-fold (95% CI: 5.39-14.4) increased risk of DCIS. Among proliferative changes with atypia BBDs, invasive cancer hazard ratios (HRs) ranged from 2.76-4.85; DCIS HRs, 5.07-8.51. Among proliferative changes without atypia BBDs, invasive HRs ranged from near-null (papillomatosis) to moderate and strong associations (e.g., HR=1.55 for usual ductal hyperplasia and 2.84 for multiple papillomas); DCIS HRs=1.37-5.04. Nonproliferative BBDs were associated with low-to-moderate risk (invasive HRs=0.63 for atrophy to 2.16 for benign breast parenchyma; DCIS HRs=0.66-4.29). Most associations declined with increasing time since biopsy.

Associations between BBDs and breast cancer varied widely within commonly used histologic categories.

Advancing knowledge of specific BBD diagnoses may improve breast cancer risk prediction and support targeted screening and prevention strategies.