PMID- 36077795 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 17 DP - 2022 Aug 31 TI - Can HER2 1+ Breast Cancer Be Considered as HER2-Low Tumor? A Comparison of Clinicopathological Features, Quantitative HER2 mRNA Levels, and Prognosis among HER2-Negative Breast Cancer. LID - 10.3390/cancers14174250 [doi] LID - 4250 AB - Background: Human epidermal growth factor receptor 2 (HER2)-low tumor is a new entity defined as HER2 immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization (FISH)-negative. We aimed to evaluate whether HER2 mRNA levels tested by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) could better define HER2-low tumors. Patients and methods: Consecutive breast cancer patients with hormonal receptor-positive, HER2-negative diseases, and HER2 mRNA results were included. Clinicopathologic features, HER2 mRNA expression level, and prognosis were compared among HER2 0, 1+ and 2+/FISH- groups. Concordance of the HER2 category between qRT-PCR and IHC/FISH was analyzed for each group. Results: 2296 patients were included: 368 (16.0%) HER2 0, 911 (39.7%) 1+, and 1017 (44.3%) 2+/FISH- tumors. HER2 1+ cases shared similarities with HER2 0 tumors in terms of clinicopathologic features (all p > 0.05), whereas IHC 2+/FISH- cases were less often non-IDC (p = 0.045), node-negative (p = 0.044), and Ki-67 < 14% (p <0.001). The mRNA expression was similar between HER2 0 and 1+ cases (p = 0.063), and both were lower than 2+/FISH- cases (p < 0.001). A poor concordance rate was found between IHC/FISH and qRT-PCR for HER2 0 and HER2-low cases (Cohen's kappa 0.126, p < 0.001). No survival difference was observed among these groups, whether stratified by HER2 IHC/FISH status or mRNA level (all p > 0.05). Conclusions: HER2 1+ cases had similar clinicopathological features to HER2 0 breast cancers, and both were different from HER2 2+/FISH- cases. HER2 mRNA levels were comparable between HER2 0 and 1+ tumors, and both were significantly lower than IHC 2+/FISH- tumors. Neither IHC nor qRT-PCR may be optimal to quantify HER2-low expression, especially for HER2 1+ patients. FAU - Shu, Lan AU - Shu L AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China. FAU - Tong, Yiwei AU - Tong Y AUID- ORCID: 0000-0001-5131-9095 AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China. FAU - Li, Zhuoxuan AU - Li Z AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China. FAU - Chen, Xiaosong AU - Chen X AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China. FAU - Shen, Kunwei AU - Shen K AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China. LA - eng GR - 81772797, 82072937/National Natural Science Foundation of China/ GR - 20172007/Shanghai Municipal Education Commission/ GR - 21YF1427400/Science and Technology Commission of Shanghai Municipality/ PT - Journal Article DEP - 20220831 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9455006 OTO - NOTNLM OT - HER2-low OT - breast cancer OT - immunohistochemistry OT - mRNA level OT - prognosis COIS- The authors declare no conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/10 06:01 PMCR- 2022/08/31 CRDT- 2022/09/09 01:11 PHST- 2022/08/10 00:00 [received] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/09/09 01:11 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/10 06:01 [medline] PHST- 2022/08/31 00:00 [pmc-release] AID - cancers14174250 [pii] AID - cancers-14-04250 [pii] AID - 10.3390/cancers14174250 [doi] PST - epublish SO - Cancers (Basel). 2022 Aug 31;14(17):4250. doi: 10.3390/cancers14174250.