Axillary Lymph Node Status, Adjusted for Pathologic Complete Response in Breast and Axilla after Neoadjuvant Chemotherapy, Predicts Differential Disease-Free Survival in Breast Cancer

Background: Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pCR) information into axillary lymph node restaging after neoadjuvant chemotherapy (NAC) adds significance to its prognostic values. Methods: Patients included in the analysis had stage II or III disease, with post-NAC axillary lymph node dissection (ALND), without sentinel lymph node biopsy before completion of NAC, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pCR in both breast and axilla into ypN0(pCR) and ypN0(non-pCR). Univariate and multivariate survival analyses were performed. Results: Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (HR+) and negative for the human epidermal growth factor receptor (HER2–), 101 had tumours that were positive for HER2 (HER2+), and 55 had tumours that were triple-negative. The rate of pCR in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pCR patients, the pCR patients had better disease-free survival (DFS) and overall survival (OS): p = 0.002 for DFS and p = 0.011 for OS. In non-pCR patients, DFS and OS were similar in the ypN0(non-pCR) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pCR) (n = 75), ypN0– 1(non-pCR) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year DFS was 98%, 91%, and 56%, and the 3-year OS was 100%, 91%, and 82% respectively. The differences in DFS and OS between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pCR were the only two independent factors predicting DFS. Conclusions: Axillary lymph node status after NAC, adjusted for pCR in breast and axilla, predicts differential DFS in patients without prior sentinel lymph node biopsy.