Degnim · Cancer 2016 · retrospective cohort study · n=1174

Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women.

Cited 60 times in the scientific literature.

Level 3 - non-randomized controlled study

Observational cohort study assessing cancer risk across histological strata in two independent cohorts.

PubMed 27352219 · doi:10.1002/cncr.30153 · record verified 2026-08-26

What was done

Histological samples containing atypical hyperplasia (AH) were analyzed from two independent cohorts of women with benign breast disease: the Mayo Clinic cohort (708 subjects) and the Nashville cohort (466 subjects), totaling 1,174 women. Pathologists quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). Breast cancer risk was then stratified by the number of foci (1, 2, or 3 or more) within each histological subtype.

What was found

In the Mayo cohort, increasing AH foci correlated with elevated relative risks (RR) of breast cancer for ADH (RR 2.61 for 1 focus, 5.21 for 2 foci, 6.36 for 3 or more foci; P for trend = .006) and for ALH (RR 2.56, 3.50, and 6.79, respectively; P for trend = .001). In the Nashville cohort, relative risks for ADH were 2.70 for 1 focus, 5.17 for 2 foci, and 15.06 for 3 or more foci (P for trend < .001); for ALH, relative risks were 2.61, 3.48, and 4.02, respectively (P for trend = .148). In combined analysis, breast cancer risk rose significantly across 1, 2, and 3 or more foci for both ADH (RR 2.65, 5.19, and 8.94; P < .001) and ALH (RR 2.58, 3.49, and 4.97; P = .001).

Why it matters

Quantifying the multifocality or extent of atypia in benign breast biopsies provides a clear dose-response stratification for future breast cancer risk, which can refine clinical risk assessment and guide personalized screening or chemoprevention strategies.

Limits

The abstract does not report confidence intervals, duration of follow-up, patient demographics, or potential confounding variables such as family history and hormonal exposures. Findings rely on retrospective cohort data, and the trend for ALH alone did not achieve statistical significance in the Nashville cohort.

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