HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer

Purpose: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast diseas e was associated with an increased risk of subsequent breast cancer. Patients and Methods: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic a nd who were subsequently observed for the development of breast cancer, Pat ients who developed breast cancer formed the case group, and a matched samp le from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DN A or tissue for evaluation of HER-2/neu amplification and protein overexpre ssion, Results: Among the controls, seven benign tissues (4.5%) demonstrated low-l evel HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18 %) tissue specimens from cases exhibited amplification. HER-2/neu amplifica tion in benign breast biopsies was associated with an increased risk of bre ast cancer (odds ratio [OR] = 2.2; 95% confidence interval [CI], 0.9 to 5.8 ); this association approached statistical significance, The risks for brea st cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atyp ia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal h yperplasia, For women having both HER-2/neu amplification and a proliferati ve histopathologic diagnosis (either typical or atypical), the risk of brea st cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexp ression of the HER-2/neu protein product, defined as membrane staining in 1 0% or more of epithelial cells, was found in 30% of the breast tumors but w as not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to h ave had HER-2/neu amplification in their prior benign biopsy (P = .06, Fish er's exact test). Conclusion: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at subst antially increased risk for subsequent breast cancer. (C) 2000 by American Society of Clinical Oncology.