Supplementary Material for: Neoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status

Introduction: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2) positive BC, and in estrogen receptor-positive (ER+)/ HER2- BC with high-risk features. In ER+/HER2- breast cancer, pathological complet rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status. Methods: Retrospective data analysis from Kartal Dr. Lütfi Kırdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. Results: Of 203 patients, 11.8% achieved pCR. Ki67 (p<0.001) and ER percentage (p<0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p=0.003, HR: 1.02) and ER percentage (p=0.019, HR: 0.97) as independent predictors of pCR probability. Conclusion: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤ 24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.