Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27.

The limited information on predictors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NC) has resulted in controversy about the optimal use of adjuvant radiotherapy and the timing of sentinel lymph node biopsy. We examined patterns and predictors of LRR as first event in combined analysis of two National Surgical Adjuvant Breast and Bowel Project (NSABP) neoadjuvant trials. NC was either doxorubicin/cyclophosphamide (AC) alone or AC followed by neoadjuvant/adjuvant docetaxel. Lumpectomy patients received breast radiotherapy alone; mastectomy patients received no radiotherapy. Pathologic complete response was defined as the absence of invasive tumor in the breast. Multivariate analyses were used to identify independent predictors of LRR. The primary end point was time to LRR as first event. In 3,088 patients, 335 LRR events had occurred after 10 years of follow-up. The 10-year cumulative incidence of LRR was 12.3% for mastectomy patients (8.9% local; 3.4% regional) and 10.3% for lumpectomy plus breast radiotherapy patients (8.1% local; 2.2% regional). Independent predictors of LRR in lumpectomy patients were age, clinical nodal status (before NC), and pathologic nodal status/breast tumor response; in mastectomy patients, they were clinical tumor size (before NC), clinical nodal status (before NC), and pathologic nodal status/breast tumor response. By using these independent predictors, groups at low, intermediate, and high risk of LRR could be identified. Nomograms that incorporate these independent predictors were created. In patients treated with NC, age, clinical tumor characteristics before NC, and pathologic nodal status/breast tumor response after NC can be used to predict risk for LRR and to optimize the use of adjuvant radiotherapy.