Breast Cancer Risk and Progressive Histology in Serial Benign Biopsies

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.

Figure 1.

Incidence of breast cancer by histological impression in the multiple biopsy cohort. Cumulative incidence of breast cancer post–second biopsy by histologic impression category at second biopsy using the competing risk approach with death modeled as a competing event. The P value was calculated using a two-sided Gray’s test for equality. AH = atypical hyperplasia; NP = nonproliferative disease; PDWA = proliferative disease without atypia.

Figure 2.

Incidence of breast cancer by histological impression by change in histological impression. A) Cumulative incidence of breast cancer post–second biopsy by histologic progression at subsequent biopsy among women with nonproliferative disease at index biopsy. B) Cumulative incidence of breast cancer post–second biopsy by histologic progression at subsequent biopsy among women with proliferative disease without atypia at index biopsy. C) Cumulative incidence of breast cancer post–second biopsy by histologic progression at subsequent biopsy among women with atypical hyperplasia at index biopsy. All curves used the competing risk approach with death modeled as a competing event. Each P value was calculated using a two-sided Gray’s test for equality. AH = atypical hyperplasia; NP = nonproliferative disease; PDWA = proliferative disease without atypia.