Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact.
Adult; Aged; Breast Neoplasms; Chromosomes, Human, Pair 17; Female; Gene Amplification; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Monosomy; Prognosis; Receptor, ErbB-2; Trastuzumab; Aneusomy 17; CEP17; Chromosome 17; FISH; HER2; HER2-amplified; Monosomy 17; Polysomy 17; Trastuzumab
PURPOSE: HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment.
METHODS: From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0.
RESULTS: Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH.
CONCLUSIONS: In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.
Women & Children
Earle A. Chiles Research Institute
Page, David B; Wen, Hannah; Brogi, Edi; Dure, Dana; Ross, Dara; Spinelli, Kateri J; Patil, Sujata; Norton, Larry; Hudis, Clifford; and McArthur, Heather L, "Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact." (2018). Articles, Abstracts, and Reports. 826.