Impact of HER2-low status on clinicopathological characteristics and pathological complete response in luminal and triple-negative early breast cancer

BackgroundHER2-low has become a clinically relevant biomarker in metastatic breast cancer. The importance of this feature in early breast cancer is investigated intensively. The present study aimed to evaluate the clinicopathological characteristics and the relationship between HER2-low status and pCR in breast cancer patients receiving neoadjuvant therapy (NAT).MethodsConsecutive patients with early HER2-negative breast cancer who underwent operation after NAT from January 2018 to December 2023 were enrolled in this study. The clinicopathological characteristics and response to NAT were retrospectively analyzed and compared between HER2-low and HER2-0 in two separate groups: luminal and triple-negative breast cancer (TNBC). pCR was defined as ypTis/0ypN0.ResultsThis study involved 958 patients who received NAT, including 655 luminal and 303 TNBC patients. All TNBC and 400 (61,0%) luminal patients received neoadjuvant chemotherapy, and the remaining hormone therapy in that setting. HER2-low accounted for 60.0% tumors. The proportion of luminal cancer in HER2-low cases was higher than in HER2-0 population (77.9 % vs. 54.0 %, p < 0.001). No clinical or histopathological characteristics of tumors differed significantly between HER2-0 and HER2-low either among luminal or TNBC patients. pCR rate of HER2-low tumors was significantly lower than HER2-0 cancers in TNBC patients (43.3 % vs. 61.9 %, p = 0.001). In luminal cancer there was no correlation between pCR rate and HER2 status (12.5% in HER2-low vs 11.1% in HER2-0; p = 0.610). Multivariate analysis showed that in TNBC cohort HER2-0 (p = 0.002), higher Ki67 (p <0.001) and cT1/2 (p = 0.008) were significantly associated with pCR rate, whereas among patients with luminal cancer neoadjuvant chemotherapy (p <0.001), histological grade 3 (p = 0.010) and higher Ki67 (p<0,001) significantly increased pCR rate.ConclusionsOur results suggest that HER2-low TNBC patients experience lower pCR rate after NAT. In our cohort, high Ki67 had predictive effect for pCR in the entire HER2-negative breast cancer patients.Legal entity responsible for the studyKatarzyna Pogoda.FundingHas not received any funding.DisclosureK. Pogoda: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Gilead, Novartis, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Sandoz, AstraZeneca; Financial Interests, Personal, Full or part-time Employment, Assistant Professor: Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Financial Interests, Personal and Institutional, Other, SI: Novartis, Roche, Eli Lilly, AstraZeneca; Non-Financial Interests, Other, Breast Cancer Group - Steering Committee Member, Quality of Life Group: EORTC; Non-Financial Interests, Member: Polish Society of Clinical Oncology, Polish Society of Oncology. W. Olszewski: Financial Interests, Personal, Invited Speaker: AstraZeneca, Gilead, Roche, MSD. A. Niwinska: Financial Interests, Personal, Invited Speaker: Novartis, Gilead. I. Lemanska: Financial Interests, Personal, Invited Speaker: Lilly, Novartis. A. Konieczna: Financial Interests, Personal, Invited Speaker: Novartis, AstraZeneca, Gilead. A. Balata: Financial Interests, Personal, Invited Speaker: Novartis. Z. Nowecki: Financial Interests, Personal, Invited Speaker: Gilead. All other authors have declared no conflicts of interest.