The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions Suzanne B. CoopeyEmanuele MazzolaJulliette M. BuckleyJohn Sharko • Ahmet K. BelliElizabeth M. H. KimFernanda Polubriaginof • Giovanni ParmigianiJudy E. GarberBarbara L. SmithMichele A. Gadd • Michelle C. SpechtAnthony J. GuidiConstance A. RocheKevin S. Hughes

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carci- noma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diag- nosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p \ 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p \ 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physi- cians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.