Characteristics of breast ducts in normal risk and high risk women and their relationship to ductal cytologic atypia

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal risk (NR) or at high-risk (HR) for sporadic breast cancer. Breast ductal cells were collected and studied cytologically and by gene expression profiling, and breast ductal architectural changes were studied by breast ductal endoscopy (BDE) and breast MRI. One-hundred-forty subjects were studied, 70 at HR (RR, 2.0 - 4.6) and 70 at NR. Cytologic atypia was present in 22.9% of HR and 25.7% of NR subjects. Ductal endoscopy was performed in 89 subjects and revealed benign intraductal abnormalities, primarily intraductal fibrous webbing suggesting chronic inflammation, in 40.4% of HR and 5.4% of NR subjects, respectively (P2 = 0.0002). Two HR subjects with atypia and no NR subjects with atypia developed invasive breast cancer. Gene expression profiling of ductal cells showed comparable gene expression profiles without enriched expression of previously defined oncogenic signatures in subjects with cellular atypia compared to those without atypia, and in HR subjects compared with NR subjects (FDR>0.5). Cytologic ductal atypia in normal risk subjects does not appear to be of clinical significance. Atypia in women at high-risk may be associated with benign and malignant breast ductal abnormalities; these characteristics of high-risk ductal cells may not be reflected in gene expression profiles. Copyright ©2020, American Association for Cancer Research.

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