Atypical ductal or lobular hyperplasia, lobular carcinoma in-situ, flat epithelial atypia, and future risk of developing breast cancer: Systematic review and meta-analysis

Background: Biopsy-proven breast lesions such as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS) and flat epithelial atypia (FEA) increase subsequent risk of breast cancer (BC), but long-term risk has not been synthesized. A systematic review was conducted to quantify future risk of breast cancer accounting for time since diagnosis of these high-risk lesions. Methods: A systematic search of literature from 2000 was performed to identify studies reporting BC as an outcome following core-needle or excision biopsy histology diagnosis of ADH, ALH, LCIS, lobular neoplasia (LN) or FEA. Meta-analyses were conducted to estimate cumulative BC incidence at five-yearly intervals following initial diagnosis for each histology type. Results: Seventy studies reporting on 47,671 subjects met eligibility criteria. BC incidence at five years postdiagnosis with a high-risk lesion was estimated to be 9.3 % (95 % CI 6.9-12.5 %) for LCIS, 6.6 % (95 % CI 4.4-9.7 %) for ADH, 9.7 % (95 % CI 5.3-17.2 %) for ALH, 8.6 % (95 % CI 6.5-11.4 %) for LN, and 3.8 % (95 % CI 1.2-11.7 %) for FEA. At ten years post-diagnosis, BC incidence was estimated to be 11.8 % (95 % CI 9.0-15.3 %) for LCIS, 13.9 % (95 % CI 7.8-23.6 %) for ADH, 15.4 % (95 % CI 7.2-29.3 %) for ALH, 17.0 % (95 % CI 7.2-35.3 %) for LN and 7.2 % (95 % CI 2.2-21.2 %) for FEA. Conclusion: Our findings demonstrate increased BC risk sustained over time since initial diagnosis of high-risk breast lesions, varying by lesion type, with relatively less evidence for FEA.