PMID- 32002765 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20210402 IS - 1573-7217 (Electronic) IS - 0167-6806 (Print) IS - 0167-6806 (Linking) VI - 180 IP - 2 DP - 2020 Apr TI - Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma. PG - 321-329 LID - 10.1007/s10549-020-05546-0 [doi] AB - PURPOSE: Patients with HER2-positive breast cancer commonly receive anti-HER2 neoadjuvant chemotherapy and pathologic complete response (pCR) can be achieved in up to half of the patients. HER2 protein expression detected by immunohistochemistry (IHC) can be quantified using digital imaging analysis (DIA) as a value of membranous connectivity. We aimed to investigate the association HER2 IHC DIA quantitative results with response to anti-HER2 neoadjuvant chemotherapy. METHODS: Digitized HER2 IHC whole slide images were analyzed using Visiopharm HER2-CONNECT to obtain quantitative HER2 membranous connectivity from a cohort of 153 HER2+ invasive breast carcinoma cases treated with anti-HER2 neoadjuvant chemotherapy (NAC). HER2 connectivity and other factors including age, histologic grade, ER, PR, and HER2 fluorescence in situ hybridization (FISH) were analyzed for association with the response to anti-HER2 NAC. RESULTS: Eighty-three cases (54.2%) had pCR, while 70 (45.8%) showed residual tumor. Younger age, negative ER/PR, higher HER2 DIA connectivity, higher HER2 FISH ratio and copy number were significantly associated with pCR in univariate analysis. Multivariate analysis demonstrated only age, HER2 DIA connectivity, PR negativity, and HER2 copy number was significantly associated with pCR, whereas HER2 DIA connectivity had the strongest association. CONCLUSIONS: HER2 IHC DIA connectivity is the most important factor predicting pCR to anti-HER2 neoadjuvant chemotherapy in patients with HER2-positive breast cancer. FAU - Li, Aidan C AU - Li AC AD - Dublin Jerome High School, Dublin, OH, USA. FAU - Zhao, Jing AU - Zhao J AD - Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Zhao, Chao AU - Zhao C AD - Center for Biostatistics, Emory University, Atlanta, GA, USA. FAU - Ma, Zhongliang AU - Ma Z AD - Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Hartage, Ramon AU - Hartage R AD - Department of Pathology, The Ohio State University, Columbus, OH, USA. FAU - Zhang, Yunxiang AU - Zhang Y AD - Department of Pathology, Weifang People's Hospital, Weifang, China. FAU - Li, Xiaoxian AU - Li X AUID- ORCID: 0000-0002-0995-1721 AD - Department of Pathology, Emory University, Atlanta, GA, USA. xli40@emory.edu. FAU - Parwani, Anil V AU - Parwani AV AD - Department of Pathology, The Ohio State University, Columbus, OH, USA. Anil.Parwani@osumc.edu. LA - eng GR - P30 CA016058/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20200130 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Biomarkers, Tumor) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Biomarkers, Tumor/*metabolism MH - Breast Neoplasms/drug therapy/metabolism/*pathology MH - Female MH - Humans MH - Image Processing, Computer-Assisted/*methods MH - Immunohistochemistry/*methods MH - Middle Aged MH - Neoadjuvant Therapy/*methods MH - Receptor, ErbB-2/antagonists & inhibitors/*metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Treatment Outcome PMC - PMC8006811 MID - NIHMS1680480 OTO - NOTNLM OT - Anti-HER2 neoadjuvant chemotherapy OT - Breast carcinoma OT - HER2 immunohistochemistry OT - Pathologic complete response OT - Quantitative digital imaging analysis COIS- Conflict of interest All authors have no financial relationship to disclose. EDAT- 2020/02/01 06:00 MHDA- 2020/11/24 06:00 PMCR- 2021/04/01 CRDT- 2020/02/01 06:00 PHST- 2019/10/09 00:00 [received] PHST- 2020/01/21 00:00 [accepted] PHST- 2020/02/01 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2020/02/01 06:00 [entrez] PHST- 2021/04/01 00:00 [pmc-release] AID - 10.1007/s10549-020-05546-0 [pii] AID - 10.1007/s10549-020-05546-0 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2020 Apr;180(2):321-329. doi: 10.1007/s10549-020-05546-0. Epub 2020 Jan 30.