PMID- 36878823 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20230622 IS - 1938-0666 (Electronic) IS - 1526-8209 (Linking) VI - 23 IP - 4 DP - 2023 Jun TI - Breast Cancer With a HER2 FISH Group 2 Result: Should HER2 Tests be Repeated? PG - 415-422 LID - S1526-8209(23)00037-X [pii] LID - 10.1016/j.clbc.2023.02.006 [doi] AB - BACKGROUND: Breast cancer with fluorescence in situ hybridization (FISH) group 2 pattern (HER2 <4 and HER2/CEP17 ratio >/=2, a subset of monosomy CEP17) was historically considered HER2-positive, but mostly HER2-negative according to updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines unless 3+ by immunohistochemistry (IHC). Therapeutic relevance of this group remained elusive, therefore we assessed if repeat IHC and FISH can assist final HER2 classification. PATIENT AND METHODS: We retrospectively reviewed HER2 FISH performed at our institution from 2014 to 2018 and identified 23 of 3554 (0.6%) breast cancer cases with at least one-time measurement of HER2 FISH categorized as group 2. Repeat HER2 tests were performed for cases with available alternative tumor samples and compared with initial testing following 2018 ASCO/CAP guidelines. RESULTS: Only 1 of 23 group 2 cases was HER2-positive, 0/18 in primary and 1/5 in metastatic/recurrent tumors. Of 13 primary tumors with repeat HER2 results; 10 (77%) remained HER2-negative; 3 (23%) changed from HER2-negative (group 2 and IHC 2+) to HER2-positive (group 1 and IHC 2+). Among 8 of these 13 patients receiving neoadjuvant systemic therapy containing anti-HER2 agent, 3 (38%) achieved pathologic complete response (pCR). Two of 3 pCR cases were HER2-positive converters on repeat testing. Three pCR cases were ER-negative or -low positive and Ki67 >/=40%, while 5 partial responders were ER-positive and Ki67 <40% (P < .05). CONCLUSION: Breast cancer with HER2 FISH group 2 result may represent heterogeneous populations of tumor cells being originated de novo or preferentially selected secondary to therapy. Repeat HER2 tests on alternative samples may be considered to guide anti-HER2 therapy. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Wang, Minhua AU - Wang M AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Ding, Qingqing AU - Ding Q AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Gu, Jun AU - Gu J AD - The University of Texas MD Anderson Cancer Center, School of Health Professions, Houston, TX. FAU - Sfamenos, Steven M AU - Sfamenos SM AD - The University of Texas MD Anderson Cancer Center, School of Health Professions, Houston, TX. FAU - Huo, Lei AU - Huo L AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Tang, Zhenya AU - Tang Z AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Sun, Hongxia AU - Sun H AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Robinson, Melissa AU - Robinson M AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Tang, Guilin AU - Tang G AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Lim, Bora AU - Lim B AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Wu, Yun AU - Wu Y AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Albarracin, Constance T AU - Albarracin CT AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Sahin, Aysegul A AU - Sahin AA AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Chen, Hui AU - Chen H AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: hchen7@mdanderson.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230212 PL - United States TA - Clin Breast Cancer JT - Clinical breast cancer JID - 100898731 RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - 0 (Ki-67 Antigen) RN - 0 (Biomarkers, Tumor) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/genetics/therapy/pathology MH - In Situ Hybridization, Fluorescence/methods MH - Receptor, ErbB-2/genetics/analysis MH - Retrospective Studies MH - Ki-67 Antigen MH - Neoplasm Recurrence, Local/genetics MH - Biomarkers, Tumor/genetics/analysis OTO - NOTNLM OT - ASCO/CAP guidelines OT - FISH OT - HER2 amplification OT - Monosomy CEP17 OT - heterogeneity COIS- Disclosure All authors declare they have no conflicts of interest. EDAT- 2023/03/07 06:00 MHDA- 2023/05/29 06:42 CRDT- 2023/03/06 22:01 PHST- 2022/12/21 00:00 [received] PHST- 2023/02/08 00:00 [revised] PHST- 2023/02/09 00:00 [accepted] PHST- 2023/05/29 06:42 [medline] PHST- 2023/03/07 06:00 [pubmed] PHST- 2023/03/06 22:01 [entrez] AID - S1526-8209(23)00037-X [pii] AID - 10.1016/j.clbc.2023.02.006 [doi] PST - ppublish SO - Clin Breast Cancer. 2023 Jun;23(4):415-422. doi: 10.1016/j.clbc.2023.02.006. Epub 2023 Feb 12.