Prognoses of Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy before Surgery: A Retrospective Analysis

SIMPLE SUMMARY: To date there is no specific analysis providing comprehensive available evidence that can guide clinical treatment options for patients with hormone receptor-positive and human epidermal growth factor receptor-2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). We conducted a retrospective study with 3070 consecutive HR+/HER2− BC patients after NAC and indicated that progesterone receptor (PR) negativity BC has a higher complete pathological response (pCR) and lower survival than PR positivity BC. PR may be used as an independent predictor for pCR and a prognosis of HR+/HER2− BC in the NAC setting. HER2-low tumors are not significantly associated with pCR or disease-free survival (DFS), but these patients have significantly lower overall survival (OS) than those with HER-0 tumors. Our research confirms the significance of PR and HER2 status associated with pCR and prognosis. ABSTRACT: Purpose: To evaluate the clinical characteristics, pathological response, and prognostic significance of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). Methods: A survival analysis was performed to detect the factors related to recurrence and death in 3070 consecutive patients with HR+/HER2− BC who received NAC from 2011 to 2022. All patients received current “standard of care” following neoadjuvant therapy based on guidelines, including surgery and adjuvant endocrine therapy. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC 2+ and fluorescence in-situ hybridization-negative. Results: The complete pathological response (pCR) (ypT0/is ypN0) rate was 14.5%. The clinical tumor size (cT), ER scores, PR status, and Ki67 levels were related to pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 82.6% and 90.4%, respectively. PR, Ki67 levels, and postmastectomy radiotherapy were independent factors for DFS and OS, and the extranodal extension (ENE) correlated with DFS. However, pCR and HER2 status were related to OS. The pCR rate in PR negativity BC was significantly higher than that in PR positivity BC (21.1% vs. 12.2%, p = 0.000), but PR negativity BC had a poorer prognosis than PR positivity BC. HER2-low BC showed high ER scores (over 50%), PR positivity, large ypT, ENE, and lymphovascular invasion but a lower pCR rate than HER2-zero BC. Patients with HER2-low BC had shorter OS than those with HER2-zero BC (p = 0.037). However, there was no difference in DFS. Conclusions: Depending on PR status and HER2 status, patients with ER positivity and HER2 negativity exhibit different pathologic complete response rates to neoadjuvant chemotherapy and long-term outcomes, especially patients with PR negativity or HER2-low status.