Neoadjuvant versus adjuvant chemotherapy in luminal B-like breast cancer: a subset analysis of the CANTO study

The benefit of neoadjuvant chemotherapy (NAC) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) remains uncertain, given low pathologically documented complete response (pCR) rates and limited long-term comparative data. We compared overall survival (OS) between NAC and adjuvant chemotherapy (AC) in luminal B-like breast cancer treated in routine practice.

Patients enrolled in the prospective French CANTO cohort between January 2012 and December 2018 with unilateral, nonmetastatic, grade 3 HR-positive/HER2-negative BC (cT2-T3N0-N3M0) treated with NAC followed by surgery or with primary surgery followed by AC were included. The primary endpoint was OS; secondary endpoints were distant recurrence-free survival (DRFS) and invasive disease-free survival; exploratory endpoints were BC-specific survival, locoregional recurrence-free survival (LRFS) and breast recurrence-free survival. Inverse probability of treatment weighting (IPTW) was applied, with weighted Kaplan-Meier estimates and Cox models.

Among 544 patients, 165 received NAC and 379 AC; median follow-up was 72 months. Breast-conserving surgery was more frequent after NAC (64% compared with 45%, P < 0.001) and the pCR rate was 19%. After IPTW, the hazard ratio for OS with NAC was 1.36 [95% confidence interval (CI) 0.94-1.97, P = 0.10] univariably and 1.62 (95% CI 1.10-2.38, P = 0.014) after multivariable adjustment. No difference was observed for DRFS (hazard ratio 1.05, 95% CI 0.80-1.38, P = 0.70). LRFS was worse with NAC (hazard ratio 2.29, 95% CI 1.15-4.58, P = 0.018) in 19 events. In interaction tests, the association with OS was confined to cN0 (hazard ratio 2.39) and cT2 (hazard ratio 1.94) disease and absent in cN+ (hazard ratio 0.83) and cT3 (hazard ratio 0.88) tumors.

NAC was associated with more locoregional recurrence without any difference in DRFS and the association with OS was confined to subgroups in whom a neoadjuvant indication is least established. These hypothesis-generating findings do not support the routine use of NAC in luminal B-like BC without an anticipated surgical benefit.