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

Abstract

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 post-diagnosis 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.

Keywords: Atypical proliferations; Biopsy; Breast cancer; Breast cancer risk; Lobular carcinoma in-situ; Mammography.

Fig. 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram of study selection process Footnote: ADH = atypical ductal hyperplasia, ALH = atypical lobular hyperplasia, LCIS = lobular carcinoma in situ, FEA = flat epithelial atypia, RCT = randomised controlled trial.

Fig. 2

Cumulative incidence of breast cancer following biopsy-proven diagnosis of lobular carcinoma in situ. Footnote: *Reported outcome is invasive breast cancer but not ductal carcinoma in situ. n = number of breast cancer cases, N = number of women at risk, CI = confidence interval.

Fig. 3

Overall incidence of breast cancer following biopsy-proven diagnosis of lobular carcinoma in situ (LCIS) or lobular neoplasia (LN), and estimated 5- and 10-year cumulative risk from meta-regression models. Reported follow-up for each study is the average follow-up period. Footnote: *Reported outcome is invasive breast cancer but not ductal carcinoma in situ. **Reported outcome is ipsilateral invasive breast cancer or ductal carcinoma in situ, and study included non-classic LCIS. n = number of breast cancer cases, N = number of women at risk, CI = confidence interval, LCIS = lobular carcinoma in situ, BC = breast cancer, LN = lobular neoplasia, ALH = atypical lobular hyperplasia.

Fig. 4

Overall incidence of breast cancer following biopsy-proven diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or ADH and/or ALH combined, and estimated 5- and 10-year cumulative risk from meta-regression models. Reported follow-up for each study is the average follow-up period. Footnote: *Reported outcome is invasive breast cancer but not ductal carcinoma in situ. n = number of breast cancer cases, N = number of women at risk, CI = confidence interval, ADH = atypical ductal hyperplasia, BC = breast cancer, ALH = atypical lobular hyperplasia.

Fig. 5

Overall incidence of breast cancer following biopsy-proven diagnosis of flat epithelial atypia (FEA), and estimated 5- and 10-year cumulative risk from meta-regression models. Reported follow-up for each study is the average follow-up period. Footnote: *Reported outcome is invasive breast cancer but not ductal carcinoma in situ. n = number of breast cancer cases, N = number of women at risk, CI = confidence interval, FEA = flat epithelial atypia, BC = breast cancer.