PMID- 26659222 OWN - NLM STAT- MEDLINE DCOM- 20161007 LR - 20220316 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 21 IP - 1 DP - 2016 Jan TI - High HER2/Centromeric Probe for Chromosome 17 Fluorescence In Situ Hybridization Ratio Predicts Pathologic Complete Response and Survival Outcome in Patients Receiving Neoadjuvant Systemic Therapy With Trastuzumab for HER2-Overexpressing Locally Advanced Breast Cancer. PG - 21-7 LID - 10.1634/theoncologist.2015-0101 [doi] AB - BACKGROUND: The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER2+ locally advanced breast cancer (LABC). PATIENTS AND METHODS: The present retrospective study included 555 patients with HER2+ LABC who had undergone NST and definitive surgery (1999-2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 3+ and/or HER2 FISH ratio of >/=2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio, either as a continuous variable or with a cutoff of >/=7.0, would predict for pCR (no invasive disease in the breast and no tumor in the ipsilateral axillary lymph nodes), RFS, and/or OS. RESULTS: The pCR group's median HER2 FISH ratio was significantly higher than that of the non-pCR group (6.4 vs. 5.2; p = .003). The logistic regression model demonstrated that the independent predictors of pCR included a high HER2 FISH ratio as a continuous variable (p = .04). The multicovariate Cox proportional hazard model showed that a high HER2 FISH ratio (with a cutoff of >/=7.0 or as a continuous variable) was a significant prognostic indicator of longer RFS time (p = .047 and p = .04, respectively). Similarly, a high HER2 FISH ratio of >/=7.0 was associated with longer OS (p = .06). CONCLUSION: A high HER2 FISH ratio is a predictor of pCR in patients with HER2+ LABC who receive NST-T. IMPLICATIONS FOR PRACTICE: This study demonstrated the optimal predictive and prognostic value of a HER2/centromeric probe for chromosome 17 FISH ratio for primary HER2+ breast cancer treated with trastuzumab combined with neoadjuvant systemic treatment (NST-T). This suggests that a high HER2 FISH ratio is a potential indicator for a high pathologic complete response rate and a better prognosis when patients are treated with NST-T. CI - (c)AlphaMed Press. FAU - Kogawa, Takahiro AU - Kogawa T AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Fouad, Tamer M AU - Fouad TM AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Liu, Diane D AU - Liu DD AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Wu, Jimin AU - Wu J AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Shen, Yu AU - Shen Y AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Masuda, Hiroko AU - Masuda H AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Fujii, Takeo AU - Fujii T AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Chavez-MacGregor, Mariana AU - Chavez-MacGregor M AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Alvarez, Ricardo H AU - Alvarez RH AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Hortobagyi, Gabriel N AU - Hortobagyi GN AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Valero, Vicente AU - Valero V AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Ueno, Naoto T AU - Ueno NT AD - Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA nueno@mdanderson.org. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151209 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage MH - Breast Neoplasms/*drug therapy/*genetics/pathology MH - Centromere/*genetics MH - Chromosomes, Human, Pair 17 MH - Disease-Free Survival MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - *Neoadjuvant Therapy MH - Paclitaxel/administration & dosage MH - Prognosis MH - Receptor, ErbB-2/*biosynthesis/genetics MH - Retrospective Studies MH - Trastuzumab/administration & dosage PMC - PMC4709200 OTO - NOTNLM OT - HER2+ breast cancer OT - HER2/centromeric probe for chromosome 17 fluorescence in situ hybridization ratio OT - Pathologic complete response OT - Predictive factor OT - Trastuzumab COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2015/12/15 06:00 MHDA- 2016/10/08 06:00 PMCR- 2017/01/01 CRDT- 2015/12/15 06:00 PHST- 2015/09/17 00:00 [received] PHST- 2015/09/21 00:00 [accepted] PHST- 2015/12/15 06:00 [entrez] PHST- 2015/12/15 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - theoncologist.2015-0101 [pii] AID - T15101 [pii] AID - 10.1634/theoncologist.2015-0101 [doi] PST - ppublish SO - Oncologist. 2016 Jan;21(1):21-7. doi: 10.1634/theoncologist.2015-0101. Epub 2015 Dec 9.