ABSTRACT
Background: More than 1 million women per year in the United States with benign breast biopsies are known to be at elevated risk for breast cancer (BC), with risk stratified on histologic categories of epithelial proliferation. Here we assessed women who had serial benign biopsies over time and how changes in the histologic classification affected BC risk. Methods: In the Mayo Clinic Benign Breast Disease Cohort of 13 466 women, 1414 women had multiple metachronous benign biopsies (10.5%). Both initial and subsequent biopsies were assessed histologically. BC risk for clinical and prognostic factors was assessed using subdistribution models to account for competing risks, and logistic regression/Wilcoxon/chi-square tests to assess covariates. All statistical tests were two-sided. Results: Breast cancer risk for women with serial biopsies, stratified by histologic category in the later biopsies, was similar to women with a single biopsy. We found that changes in histological category between initial and subsequent biopsy statistically significantly impacted BC risk. Women with nonproliferative initial findings and subsequent proliferative findings had an increased risk (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.06 to 2.94, P = .03) compared with no change. Among women with proliferative disease without atypia at initial biopsy, risk decreased if later biopsy regressed to nonproliferative (HR = 0.49, 95% CI = 0.25 to 0.98) and increased if later biopsy showed progression to atypical hyperplasia (HR = 1.49, 95% CI = 0.73 to 3.05) compared with no change ( P = .04). Conclusions: We found that breast cancer risk increases in women with progressive epithelial proliferation over time and decreases in women whose biopsies show less proliferation. This finding has important implications for effective clinical management of the 100 000 women per year who have multiple benign breast biopsies.
Subject(s)
Breast Diseases/pathology , Breast Neoplasms/etiology , Precancerous Conditions/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Breast Diseases/complications , Breast Diseases/diagnosis , Breast Diseases/epidemiology , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Cohort Studies , Disease Progression , Female , Humans , Middle Aged , Precancerous Conditions/diagnosis , Precancerous Conditions/epidemiology , Prognosis , Risk Factors , Young AdultABSTRACT
Breast papillomas may be single or multiple and associated with atypical ductal or lobular hyperplasias (ADH/ALH). The risk of breast carcinoma development in patients with papillomas, particularly those with multiple or atypical lesions, is incompletely defined. Fibrocystic lesions were histopathologically classified in a benign breast disease cohort of 9155 who underwent biopsy from 1967 to 1991, with papilloma assessment in 9108. Individuals with papillomas (N=480) were classified into 4 groups: single papilloma (SP, N=372), single papilloma with ADH or ALH (SP+A, N=54), multiple (>5) papillomas (MP, N=41), and multiple papillomas with ADH or ALH (MP+A, N=13). Those without papillomas were classified as nonproliferative (NP, N=6053), proliferative without atypia (PDWA, N=2308), and ADH/ALH [atypical hyperplasia (AH), N=267]. The relative risk of cancer development within our cohort was compared to that expected in the general population using standardized incidence ratios. The relative risk of breast cancer development associated with SP [2.04, 95% confidence interval (CI) 1.43-2.81] was greater than NP (1.28, 95% CI 1.16-1.42) but similar to PDWA (1.90, 95% CI 1.66-2.16). The risk associated with SP+A (5.11, 95% CI 2.64-8.92) was highly elevated but not substantively different than atypical hyperplasia (4.17, 95% CI 3.10-5.50). Patients with MP are at increased risk compared with PDWA or SP (3.01, 95% CI 1.10-6.55), particularly those with MP+A (7.01, 95% CI 1.91-17.97). There was a marginal increase in breast cancer risk (16%) among patients with proliferative disease if a papilloma was present, but this did not reach statistical significance (P=0.29). The observed frequency of ipsilateral (vs. contralateral) breast cancer development in papilloma subsets was not significantly different than other patient groups. We conclude that SP imparts a cancer risk similar to conventional proliferative fibrocystic change. The presence of papilloma in, or associated with, atypia does not modify the risk connotation of ADH/ALH overall. MP constitutes a proliferative breast disease subset having unique clinical and biologic behavior.
