Association of HER-2 Copy Number and HER-2/CEP-17 Ratio with Neoadjuvant Taxane-Containing Chemotherapy Sensitivity in Locally Advanced Breast Cancer

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to:Compare the clinical value of copy number–based fluorescence in situ hybridization (FISH) versus HER-2/CEP-17 ratio-based FISH in identifying patients who may benefit from taxane-containing neoadjuvant chemotherapy.Consider the implications of HER-2 copy number and aneusomy 17 when making treatment decisions in patients with locally advanced breast cancer. CME This article is available for continuing medical education credit at CME.TheOncologist.com Purpose. Aneusomy 17 causes inconsistency in fluorescence in situ hybridization (FISH)-based human epidermal growth factor receptor (HER)-2 status assessment using different algorithms (copy number or the HER-2/centromere enumerator probe 17 [CEP-17] ratio). We investigated the effects of FISH-based HER-2 status assessment and aneusomy 17 on responsiveness to neoadjuvant chemotherapy (NAC). Patients and Methods. This prospective study recruited 152 patients with locally advanced breast cancer who underwent four-cycle weekly paclitaxel plus carboplatin without trastuzumab. Results. The pathologic complete remission (pCR) rate in the breast and axilla was 24.3% (95% confidence interval [CI], 17.7%–32.0%). Although HER-2 status, assessed by either HER-2/CEP-17 ratio–based FISH or copy number–based FISH, was a predictor of NAC sensitivity, ratio–assessed HER-2 status had a poorer performance in determining patients' responsiveness to NAC (p = .029). Patients who were not HER-2 amplified when assessed using the HER-2/CEP-17 ratio but were HER-2 amplified when assessed using copy number (∼5%) were eventually proven to be responsive to NAC, with a pCR rate of 57% (95% CI, 18.4%–90.1%). In contrast, patients who were HER-2 amplified when assessed by the ratio but not HER-2 amplified when assessed using copy number (∼3%) were completely irresponsive. Higher HER-2 copy numbers represented increasing chances of a pCR (adjusted odds ratio, 3.09; 95% CI, 1.35–7.08), with an apparent gene–dose effect (p for trend < .001). Conclusion. It is likely that HER-2 copy number but not the HER-2/CEP-17 ratio determines NAC sensitivity. Additional studies to validate our findings are warranted.