Abstract PS3-09-22: Er expression and age as key determinants of pathologic complete response (pcr) following neoadjuvant chemotherapy in patients with hormone receptor-positive, her2-negative early breast cancer. real world data

Abstract Background: Neoadjuvant chemotherapy remains a cornerstone in the treatment of patients with early-stage breast cancer and improves survival outcomes. Achievement of pathological complete response (pCR) have always been considered as a surrogate marker for better survival in patients with breast cancer and has been used as a primary endpoint in multiple clinical trials. However, patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative disease typically achieve low rates of pCR. Better understanding of the potential clinical and pathological variables affecting pCR in such population is important. Methods: This was a retrospective cohort analysis we conducted using electronic clinical and pathological data from patients diagnosed with early-stage breast cancer at one institution. All eligible patients included in the analysis had early HR+/HER2-negative disease: stage I, II, or III as per the American Joint Committee on Cancer (AJCC) 8th edition. Estrogen receptor (ER) expression by immunohistochemistry was stratified as: High (ER 50%), intermediate (11-50%), low (1-10%) and negative (0%). Multivariable logistic regression was performed to identify independent predictors of pCR. We used multivariable logistic regression analysis to identify independent clinical and/or pathological predictors for pCR. Results: Out of 2724 patients included in the analysis; 1039 patients were treated with neoadjuvant chemotherapy. Median age was 50 (22-83) years. Most (n= 864, 83.1%) patients had invasive ductal carcinoma (IDC), while (n= 92, 8.8%) patients had invasive lobular carcinoma (ILC). Majority (n=870, 83.7%) patients had high ER-expression; 44 patients (4.2%) intermediate ER-expression, 59 patients (5.6%) low ER-expression, while 63 patients (6%) had ER-negative (but PR-positive) disease. 758 (72.9%) had clinical node-positive disease. The overall pCR rate in this population was 10.9% (n=114). Younger age was significantly associated with higher pCR rates: 15.0% in patients 45 years, compared to 8.7% in those aged 45-64 (adjusted OR: 0.52; 95% CI: 0.33-0.81; p=0.004), and 4.9% in patients ≥65 years. Histological subtype was not a significant predictor of pCR. Patients with ILC had a lower pCR rate (5.4%) compared to those with IDC (10.5%), but this difference was not statistically significant (adjusted OR: 0.90; 95% CI: 0.30-2.19; p=0.838). ER expression was a strong independent predictor of pCR. Compared to tumors with high ER expression (pCR rate: 6.4%), significantly higher pCR rates were observed in tumors with low ER expression (42.4%; OR: 10.35; p0.001) and ER-negative/PR-positive tumors (39.7%; OR: 8.96; p0.001). Tumors with intermediate ER expression also showed an increased pCR rate (18.2%; OR: 2.40; p=0.042). Clinical nodal status was not independently associated with pCR. Additionally, patients with HER2-zero tumors had higher pCR rates compared to those with HER2-low disease (IHC 1+ or 2+ with negative FISH), although this difference did not reach statistical significance. Conclusion: Our analysis showed consistent findings with previously published data worldwide informing a low rate of pCR in this population. This confirms that HR+ breast cancer carries a significant resistance to chemotherapy and validates ER-expression as an important biomarker for responsiveness to chemotherapy. Younger age and lower ER-expression are strong independent predictors of response. Such findings could influence tailored treatment approaches and the use of personalized therapeutics, as well as exploring different neoadjuvant strategies using targeted agents among others. Citation Format: M. Horani, F. Tamimi, T. Al-Batsh, O. El Khatib, B. Sharaf, Y. Al-Masri, A. Ghanem, Q. Jawarneh, M. AL-yag'oub, A. Jaffal, R. Khader, S. Abdel-Razeq, A. Alanani, M. El-Atrash, M. Abunasser, H. Abdel-Razeq. Er expression and age as key determinants of pathologic complete response (pcr) following neoadjuvant chemotherapy in patients with hormone receptor-positive, her2-negative early breast cancer. real world data 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 PS3-09-22.