Predictors of Pathological Complete Response in Hormone Receptor-Negative HER2-Positive Breast Cancer Receiving Neoadjuvant Therapy
Aykut Özmen, Gökmen Umut ErdemNeoadjuvant anti-HER2-based therapy has significantly improved pathological complete response (pCR) rates in HER2-positive breast cancer. Hormone receptor-negative/HER2-positive (HR-/HER2+) tumors are known to demonstrate higher sensitivity to chemotherapy and HER2-targeted agents; however, predictive factors associated with pCR within this biologically distinct subgroup remain insufficiently defined. This study aimed to evaluate clinicopathological and laboratory factors associated with pCR in HR-/HER2+ breast cancer patients treated with neoadjuvant therapy. MethodsObjectives
Objectives: Neoadjuvant anti-HER2-based therapy has significantly improved pathological complete response (pCR) rates in HER2-positive breast cancer. Hormone receptor-negative/HER2-positive (HR-/HER2+) tumors are known to demonstrate higher sensitivity to chemotherapy and HER2-targeted agents; however, predictive factors associated with pCR within this biologically distinct subgroup remain insufficiently defined. This study aimed to evaluate clinicopathological and laboratory factors associated with pCR in HR-/HER2+ breast cancer patients treated with neoadjuvant therapy. Methods: This study retrospectively evaluated 57 patients with HR-negative/HER2-positive breast cancer who underwent neoadjuvant HER2-targeted treatment followed by curative-intent surgery at XXX between January 2020 and January 2024. Data regarding patient characteristics, tumor features, laboratory measurements, treatment patterns, and surgical management were extracted from electronic health records and analyzed retrospectively. Pathological complete response was defined as ypT0/isN0. Univariate and multivariate logistic regression analyses were performed to identify predictors associated with pCR. Results: Among 57 patients, 40 (70.2%) achieved pCR. The pCR cohort predominantly consisted of patients with histological grade III tumors (85.0% vs. 15.0% for grade I–II, p=0.002) and normal baseline CA 15-3 levels (87.5% vs. 12.5% for elevated, p=0.01). Other variables, including age, body mass index, menopausal status, tumor size, nodal status, Ki-67 index, CEA levels, and inflammatory markers, showed no significant association with pCR. Multivariate analysis confirmed grade III disease (OR: 9.0; 95% CI: 2.14–37.9; p=0.003) and normal CA 15-3 levels (OR: 7.1; 95% CI: 1.54–32.8; p=0.01) as independent predictors of pCR. Conclusion: In HR-/HER2+ breast cancer, high histological grade and normal baseline CA 15-3 levels independently predict pCR following neoadjuvant anti-HER2 therapy. These findings can optimize risk stratification and personalize treatment in this aggressive subtype. Keywords: CA 15-3, HER2-positive breast cancer, histological grade, hormone receptor-negative, neoadjuvant therapy, pathological complete response
Cite This Article
Özmen A, Erdem G. Predictors of Pathological Complete Response in Hormone Receptor-Negative HER2-Positive Breast Cancer Receiving Neoadjuvant Therapy. EJMI. 2026; 10(3): 312-318
Corresponding Author: Aykut Özmen