Magnitude and Laterality of Breast Cancer Risk According to Histologic Type of Atypical Hyperplasia: Results from the Nurses' Health Study

Background: Atypical hyperplasia (AH) in a benign breast biopsy is associated with an increased breast cancer risk. However, the influence of the histologic type of AH on the magnitude and laterality of breast cancer risk is poorly defined.

Methods: The authors conducted a case-control study of benign breast disease and breast cancer risk nested within the Nurses' Health Study (395 cases, 1610 controls). Benign breast biopsy slides were reviewed and categorized as showing nonproliferative lesions, proliferative lesions without atypia, or AH. Slides that showed AH were categorized further as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH).

Results: The odds ratio (OR) for breast cancer among all women with AH was 4.1 (95% confidence interval [95% CI], 2.9-5.8). However, among premenopausal women, breast cancer risk was higher for women with ALH (OR, 7.3; 95% CI, 3.8-14.2) than for women with ADH (OR, 3.1; 95% CI, 2.0-4.8). Overall, 58.9% of invasive breast cancers that developed in women with AH were in the ipsilateral breast, and the frequency of ipsilateral breast cancer was similar for women with ALH (61.3%) and women with ADH (55.9%; P = .66).

Conclusions: Women with AH in a benign breast biopsy were at a substantially increased risk for the development of breast cancer. Among premenopausal women, the risk appeared to be greater for those with ALH than those with ADH. Because only approximately 60% of cancers that develop in women with AH occur in the ipsilateral breast, for the purposes of clinical management, these lesions are viewed best as markers of a generalized (bilateral) increase in breast cancer risk.