A pooled analysis of nine prospective neoadjuvant breast cancer trials that aimed to identify independent predictors of Locoregional recurrence risk after neoadjuvant chemotherapy has been published in European Journal of Cancer.
In the neoadjuvant setting, pathological complete response (pCR) is a strong prognostic factor for recurrence and survival particularly in the most aggressive breast cancer (BC) subtypes, such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC (TNBC) Although neoadjuvant chemotherapy (NACT) is an option to allow for breast-conserving surgery (BCS) or to study new drugs and regimens, limited information about predictors of locoregional recurrence risk (LRR) is described in this setting. Therefore, the main aim of this pooled analysis was to estimate the cumulative LRR incidence rates after NACT overall and within subgroups and to identify potential predictors of LRR in this setting. A total of 10,075 women with primary BC from nine neoadjuvant trials were included. The primary outcome was the cumulative incidence rate of LRR as the first event after NACT. Distant recurrence, secondary malignancy or death were defined as competing events. For identifying LRR predictors, surgery type, pCR, BC subtypes and other potential risk factors were evaluated. The median follow-up in the entire cohort was 67 months (range 0-215 months). The location of the first relapse was locoregional in 9.5% of patients, distant in 14.5% and both in 1.7%. Overall, 5-year cumulative LRR incidence rates were 7.8% among patients treated with BCS and 11.3% with mastectomy; 4.1% in patients achieving pCR vs 9.5% in non-pCR patients; 6.0% in hormone receptor-positive/HER2-negative, 7.6% in hormone receptor-positive/HER2-positive, 10.5% in hormone receptor-negative/HER2-positive and 14.4% in TNBC. Younger age, clinically positive lymph nodes, G3 tumors, non-pCR and TNBC but not surgery type were significant independent predictors of LRR in multivariate analysis. Among BC subtypes, 5-year cumulative LRR rates were associated with higher risk in non-pCR versus pCR patients, which was significant for hormone receptor-positive/HER2-negative (5.9% vs 3.9%; hazard ratio [HR]=2.32 [95%CI 1.22-4.43]; p=0.011); hormone receptor-negative/HER2-positive (14.8% vs 3.1%; HR=4.26 [94%CI 2.35-7.71]; p<0.001) and TNBC (18.5% vs 4.2%; HR=4.10 [95%CI 2.88-5.82]; p<0.001) but not for hormone receptor-positive/HER2-positive (8.1% vs 4.8%; HR=1.56 [95%CI 0.85-2.85]; p=0.150). Within non-pCR subgroup, LRR risk was higher for hormone receptor-negative/HER2-positive and TNBC vs hormone receptor-positive/HER2-negative BC (HR=2.05 [95%CI 1.54-2.73]; p<0.001 and HR=2.77 [95%CI 2.27-3.39]; p<0.001, respectively). The results from this pooled analysis might contribute to the decision of adjuvant radiotherapy after mastectomy in high-risk patients. Hence, there is a clear need to investigate better multimodality therapies in the post-neoadjuvant setting for high-risk patients.
Werutsky G, Untch M, Hanusch C, Fasching PA, Blohmer JU, Seiler S, Denkert C, Tesch H, Jackisch C, Gerber B, Schneeweiss A, Link T, Krug D, Huober J, Rhiem K, Kühn T, Vladimirova V, Nekljudova V, Loibl S. Locoregional recurrence risk after neoadjuvant chemotherapy: A pooled analysis of nine prospective neoadjuvant breast cancer trials. Eur J Cancer. 2020;130:92-101.