Axillary Response in Patients Undergoing Neoadjuvant Endocrine Treatment for Node-Positive Breast Cancer: Systematic Literature Review and NCDB Analysis

Background: Several studies have proven that neoadjuvant endocrine therapy (NET) has a similar beneficial therapeutic effect in estrogen-positive (ER⁺) breast cancer (BC) with improved breast conservation rate in patients undergoing NET versus neoadjuvant chemotherapy (NAC). The impact of axillary complete pathologic response (pCR) is less clear. We evaluate the impact of NET on axillary downstaging and surgical management. Methods: Using the National Cancer Database (NCDB), we identified all patients with node positive (N⁺), ER⁺, HER²⁻ BC undergoing NET and performed a systemic review of literature using PRISMA guidelines. Results: The literature review identified 1479 clinically N⁺ patients in four studies, 148 of whom had axillary pCR (10.0%). In the two studies of patients with invasive lobular carcinoma (ILC), 7.8% (69/883) of clinically N⁺ patients had axillary pCR. The NCDB query identified 4580 female patients with clinically N⁺ ER⁺ HER²⁻ BC who underwent NET from 2010 to 2016 with mean age of 61.4 years. Patients who achieved a pCR were more likely to have N1 disease (p 0.008), moderately differentiated tumors (p 0.003), and ductal histology (p 0.04). There was no statistically significant difference in race, comorbidity score, education, income, hospital setting, or clinical tumor stage. Of the 4580 total patients, 663 (14.48%) had an axillary pCR (pN0) after NET, and 3917 (85.52%) remained pN+. Conclusions: We found that patients who underwent NET for N⁺ disease had a higher axillary pCR than previously reported (10%) in smaller studies. Although NET is not a common treatment option for women with N⁺ ER⁺ HER²⁻ BC, it may be a suitable option for axillary downstaging, which is currently underutilized.