PMID- 22561335 OWN - NLM STAT- MEDLINE DCOM- 20121112 LR - 20220316 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 17 IP - 6 DP - 2012 TI - Association of HER-2 copy number and HER-2/CEP-17 ratio with neoadjuvant taxane-containing chemotherapy sensitivity in locally advanced breast cancer. PG - 792-800 LID - 10.1634/theoncologist.2011-0381 [doi] AB - 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. FAU - Yu, Ke-Da AU - Yu KD AD - Department of Breast Surgery, Cancer Center and Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai, P.R. China. FAU - Liu, Guang-Yu AU - Liu GY FAU - Zhou, Xiao-Yan AU - Zhou XY FAU - Zhou, Ying AU - Zhou Y FAU - Wu, Jiong AU - Wu J FAU - Chen, Can-Ming AU - Chen CM FAU - Shen, Zhen-Zhou AU - Shen ZZ FAU - Shao, Zhi-Ming AU - Shao ZM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120504 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antineoplastic Agents) RN - 0 (Bridged-Ring Compounds) RN - 0 (Taxoids) RN - 1605-68-1 (taxane) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Algorithms MH - Antineoplastic Agents/*therapeutic use MH - Axilla/pathology MH - Breast Neoplasms/*drug therapy/*genetics/pathology MH - Bridged-Ring Compounds/*therapeutic use MH - Carboplatin/therapeutic use MH - *Chromosomes, Human, Pair 17 MH - Female MH - Gene Dosage MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Logistic Models MH - Middle Aged MH - Neoadjuvant Therapy MH - Paclitaxel/therapeutic use MH - Prospective Studies MH - Receptor, ErbB-2/*genetics/metabolism MH - Taxoids/*therapeutic use MH - Young Adult PMC - PMC3380878 COIS- Disclosures: The authors indicated no financial relationships. Section Editors: Gabriel Hortobagyi: Allergan, Genentech, sanofi-aventis, Novartis (C/A); Novartis (RF); Kathleen Pritchard: Novartis, Roche, AstraZeneca, Pfizer, Abraxis, Boehringer-Ingelheim (C/A), (RF) Reviewer "A" : Genentech (C/A); Novartis, GlaxoSmithKline (RF) Reviewer "B": WntResearch Inc. (E); TIMP-1 as biomarker (IP); DAKO A/S, Exiqon A/S, WntResearch (C/A), The Danish Cancer Society, The Danish Strategic Research (RF); Exiqon A/S (O) Reviewer "C": Roche International (C/A); Roche Canada (H), (RF) Reviewer "D": None EDAT- 2012/05/09 06:00 MHDA- 2012/11/13 06:00 PMCR- 2013/06/01 CRDT- 2012/05/08 06:00 PHST- 2012/05/08 06:00 [entrez] PHST- 2012/05/09 06:00 [pubmed] PHST- 2012/11/13 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - theoncologist.2011-0381 [pii] AID - 3779434 [pii] AID - 10.1634/theoncologist.2011-0381 [doi] PST - ppublish SO - Oncologist. 2012;17(6):792-800. doi: 10.1634/theoncologist.2011-0381. Epub 2012 May 4.