Abstract Background: Current guidelines do not mandate routine evaluation of ER, PR, and HER2 in residual tumor after neoadjuvant therapy (NAT), including chemotherapy, targeted therapy, and immune checkpoint inhibitors, in breast cancer. There are no studies that evaluated the stability of these biomarkers in inflammatory breast cancer (IBC) after NAT. We examined expression of ER, PR, and HER2 by immunohistochemistry (IHC) in residual tumor after NAT in IBC and compared the values with baseline values to determine changes in biomarker status. Methods: We included 81 IBC patients with residual tumor in mastectomy specimens after NAT. IHC analysis was performed on routinely processed tissue sections of the residual invasive breast tumor using antibodies against ER (6F11, Leica), PR (16, Leica), and HER2 (4B5, Roche/Ventana). The American Society of Clinical Oncology/College of American Pathologists criteria for scoring ER/PR/HER2 were followed. The associations between expression of ER, PR, and HER2 (positive vs. not) at baseline in the core biopsy specimen obtained as standard of care and in residual tumor in the mastectomy specimen was measured with the kappa statistic and 95% confidence intervals (CIs), using the weighted kappa for the combination of ER/PR and HER2. Results: Of the 81 patients in the study, 63 (78%) had invasive ductal tumors, and 18 (22%) had other tumor types (mixed ductal and lobular, lobular, micropapillary, mucinous, and metaplastic). The IHC findings at baseline and after NAT and alterations in invasive tumor subtypes are summarized in Table 1. Alterations in ER, PR, ER/PR, and HER2 status occurred in 10%, 22%, 12%, and 12%, respectively, of IBC patients treated with NAT. After NAT, 15 patients had low and 14 had ultralow HER2 expression (29/81, 36%). Conclusions: 1.Alterations in ER/PR/HER2 status occurred in 22% that resulted in a change in invasive tumor subtype in 22% of IBC patients.2. Low levels of HER2 expression (HER2 low and ultralow) in 36% of IBC patients may provide options for targeted therapy.3.Evaluation of ER/PR/HER2 status in residual tumor after NAT in IBC may be considered to determine the altered expression of biomarkers, which has implications for prognosis and response to adjuvant therapy. Citation Format: S. Krishnamurthy, R. S. Tidwell, M. Kai, L. Villareal, H. Lopez, B. Lim, A. Nazrazadani, R. Layman, S. Saleem, S. X. Sun, A. Lucci, V. Valero, W. Woodward, MDACC Inflammatory Breast Cancer team. Stability of Estrogen receptor (ER), Progesterone receptor (PR), and Human epidermal growth factor receptor 2 (HER2) in Residual Invasive Tumor after Neoadjuvant Therapy in Inflammatory Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD2-02.
Krishnamurthy et al. (Tue,) studied this question.