Analysis of factors associated with loco-regional failure in breast cancer patients following neoadjuvant chemotherapy.

PURPOSE/

objectivesFor patients undergoing neoadjuvant chemotherapy (NAC), many clinical factors were identified to be associated with failure. Yet, for patients achieving pathologic complete response (pCR), it remains unknown what factors are associated with any subsequent failures. Our goal is to assess the patterns and predictors of locoregional failure (LRF), distant failure (DF), and invasive disease-free survival (IDFS) post-NAC, with a particular focus on those who achieved pCR. METHODS/MATERIALS: Between 2000 and 2021, we retrospectively reviewed 1115 consecutive patients in a single-institution database following NAC. Multivariable analysis was performed using the Cox proportional hazards model to identify the independent predictors of LRF, DF, and IDFS for the entire cohort and stratified by type of breast surgery. A univariable analysis was conducted to ascertain the independent predictors of any failure (IDFS) among patients who achieved pCR in both the breast and axilla.

resultsThe median follow-up was 8.0 years [interquartile range: 4.1-12.4 years]. For the entire cohort, the 15-year cumulative incidence rates were 9.7% for LRF and 27.4% for DF, and the 15 year IDFS was 69.6%. The 15-year IDFS rates were 73.6% and 67.2% in breast-conserving surgery (BCS) and mastectomy cohorts, respectively (HR = 0.76, p = 0.03). On multivariable analysis, we found that LVI, ECE, number of malignant LNs post-NAC, triple-negative disease (TNBC), and tumor size were associated with IDFS for mastectomy patients, while achieving pCR in the breast was associated with a decreased risk for any failure. For BCS patients, the number of malignant LNs post-NAC, and TNBC were associated with IDFS, while achieving pCR in the axilla was associated with a decreased risk for any failure. On univariable analysis, we found that cT3-4 vs. cT1-2 pre-NAC was significantly associated with inferior IDFS among patients who achieved pCR in both the breast and axilla (n = 209). Patients with cN0 pre-NAC had a lower, albeit non-significant, risk of IDFS events. In patients with cN-positive disease pre-NAC who achieved pCR in both the breast and axilla (n = 117), RNI or PMRT (n = 95) did not significantly impact IDFS compared to those without RNI or PMRT (n = 22), with a median time to IDFS post-pCR of 7.1 years vs. 7.8 years, respectively.

conclusionWe identified predictors of failure in this cohort, including among patients who achieved pCR. The median time to failure after pCR is around 7 years with or without adjuvant RNI/PMRT, highlighting the need to wait for mature results from the B51 trial and warranting further follow-up.