Abstract P1-04-03: Prognostic and predictive implications of monosomy 17 in curable HER2-amplified breast cancer
Authors: Page David , Wen Yong H , Dure Dana , Hudis Clifford , Brogi Edi , McArthur Heather 
Published: May 2015

Background: Monosomy of chromosome 17 is identified in approximately 6% of HER2-amplified breast cancers. Monosomy 17 has been retrospectively associated with inferior response to trastuzumab in the metastatic setting. The adverse impact of monosomy 17 could be related to the loss of putative genes encoding DNA-binding regulatory proteins, such as ROX or TOP2A. To date, the prognostic or predictive significance of monosomy 17 in women with potentially curable HER2-positive breast cancer has not been fully evaluated.

Methods: Through a search of institutional databases, we identified women with HER2+ breast carcinoma with monosomy 17 by fluorescence in situ hybridization (FISH) and treated at our center between 1/1/00 and 6/1/11. HER2-amplification was defined as a HER2/CEP17 copy ratio ≥2.0, and monosomy 17 was defined as the presence of ≤1.4 CEP17 copies/cell. Clinical outcomes were determined by chart review, defined by Standardized Definitions for Efficacy (STEEP). Differences in treatment and other disease characteristics were compared by the log-rank test.

Results: We identified 99 women with stage I-III HER2-positive breast cancer showing monosomy 17 by FISH: 51% (n=50) were treated with trastuzumab plus chemotherapy (tras/chemo), 31% (n=31) with chemotherapy (chemo alone), and 18% (n=18) with neither (no tras/chemo). An adjuvant anthracycline was administered in 82% of women in the tras/chemo group and 97% of women in the chemo group. The 3 treatment groups were balanced for age (median: tras/chemo 49y; chemo 53y; neither 56y), but were not balanced for hormone receptor (HR)-status (HR+: tras/chemo 96%; chemo 81%; neither 78%, p=0.04) or TNM stage (stage III: tras/chemo 16%; chemo 27%; neither 0%, p=0.01). With a median follow-up of 7y (0.16-13.4y), 4y distant relapse free survival (DRFS) was 100% for the tras/chemo group, 87% for the chemo alone group, and 80% for the no tras/chemo group (p=0.018); and 4y overall survival (OS) was 100% for the tras/chemo group, 93% for the chemo alone group, and 81% for the no tras/chemo group (p=0.005).

Conclusions: Here we report the largest retrospective series of patients with curable HER2-amplified breast cancer and monosomy 17. HER2-amplified monosomy 17 does not appear to adversely affect survival in the curative setting, with outcomes comparable to those reported in large phase III adjuvant trastuzumab trials. Despite receiving less anthracycline-based chemotherapy, better OS and DRFS were observed in women treated with tras/chemo compared with women treated with chemo alone, thereby supporting the critical role of trastuzumab in this patient population, despite data to the contrary from the metastatic setting.

Citation Format: David Page, Yong H Wen, Dana Dure, Clifford Hudis, Edi Brogi, Heather McArthur. Prognostic and predictive implications of monosomy 17 in curable HER2-amplified breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-04-03.