Abstract PO3-02-07: HER2-low status in inflammatory breast cancer (IBC) is associated with hormone receptors positivity but not with pathological response to neoadjuvant chemotherapy or overall survival

Abstract Background: Half of HER2-negative breast cancers (BC) show HER2-low expression. The strong efficacy of recent anti-HER2 antibody-drug conjugates (ADC) in HER2-low tumors has risen the interest of HER2-low as a proper BC subtype. However, HER2-low non-inflammatory breast cancer (non-IBC) appears to have only marginal clinicopathological differences compared to HER2-0. Little is known about HER2-low clinical significance in IBC. Methods: Data from patients diagnosed with HER2-negative IBC between 1990 and 2021 were collected from the Institut Paoli-Calmettes European Comprehensive Cancer Center database. Two tumor groups were defined (HER2-low and HER2-0). HER2-low tumors were defined by HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-0 by IHC score of 0+. Hormone Receptor (HR) status was determined according to the French guidelines (oestrogen and/or progesterone receptors by IHC with a 10% threshold for HR-positivity). Clinicopathological characteristics, pCR (defined as ypT0/ypTis and pN0sn or ypN0), and OS rates were compared between the two tumor groups. Results: The individual data of 256 IBC patients were analyzed. Thirty-seven percent of tumors were HER2-low and 63% were HER2-0. Among patients with stage III (n = 226) and stage IV (n = 30) IBC, 35% and 53% had HER2-low tumors, respectively. HR positivity, age over 50 years, SBR grade, and menopausal status were associated with HER2-low in univariate analysis, but only HR positivity remained significant in a binary logistic regression (OR: 1.95 1.06-3.58; p=3.15E-02). In stage III patients, the pCR rate after neoadjuvant chemotherapy was similar in HER2-low (24%) and HER2-0 (29%) patients (p=0.550). No difference was observed by analyzing pCR by HR status. In univariate analysis, overall survival was affected by the clinical axillary lymph node invasion the presence of metastasis, the pathological type and menopausal status, but not by HER2 status. Conclusion: In IBC, HER2-low is associated with HR positivity but has no effect on pathological response to chemotherapy and overall survival in our retrospective cohort, consistently with data available in non-IBC patients. Of 256 IBC patients, 37% were HER2-low. These results may be useful to design future clinical trials testing anti-HER2 ADCs in IBC. Citation Format: Alexandre de Nonneville, Pascal FINETTI, Laurys Boudin, Lucas Usclade, Patrice Viens, Frederic VIRET, Emilie Mamessier, Anthony Gonçalves, François BERTUCCI. HER2-low status in inflammatory breast cancer (IBC) is associated with hormone receptors positivity but not with pathological response to neoadjuvant chemotherapy or overall survival abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-07.