The prognostic value of lymph node involvement after neoadjuvant chemotherapy is different among breast cancer subtypes

Abstract

IntroductionThe three different breast cancer subtypes (Luminal, HER2-positive and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype.MethodsWe retrospectively evaluated axillary involvement (0, 1 to 3 positive nodes, ≥ 4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into 3 classes (0; [1-3];4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.Results1197 patients were included in the analysis (luminal (n = 526, 43.9%), TNBCs (n = 376, 31.4%), HER2-positive BCs (n = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (Pinteraction= 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR=2.8; 95% CI [1.93;4.06], p<0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR=1.24, 95% CI = [0,86;1.79]). In patients with TNBC, both 1-3N+ and ≥ 4 N+ classes were associated with a decreased RFS (HR=3.19, 95%CI= [2.05; 4.98] and HR=4.83, 95%CI= [3.06; 7.63], respectively versus ypN0, p< 0.001). Similar decreased prognosis were observed among patients with HER2-positive BC (1-3N+: HR=2.7, 95%CI= [1.64; 4.43] and ≥ 4 N+: HR=2.69, 95%CI= [1.24; 5.8] respectively, p=0.003).ConclusionThe prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.