The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes

Lucie Laot; Enora Laas; Noemie Girard; Elise Dumas; Eric Daoud; Beatriz Grandal; Jean-Yves Pierga; Florence Coussy; Youlia Kirova; Elsy El-Alam; Guillaume Bataillon; Marick Lae; Florence Llouquet; Fabien Reyal; Anne-Sophie Hamy

doi:10.3390/cancers13020171

The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes

Cancers (Basel). 2021 Jan 6;13(2):171. doi: 10.3390/cancers13020171.

Authors

Affiliations

¹ Department of Surgical Oncology, Institute Curie, University Paris, 75005 Paris, France.
² Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, INSERM, University Paris, 75005 Paris, France.
³ Department of Medical Oncology, Institute Curie, University Paris, 75005 Paris, France.
⁴ Department of Radiotherapy, Institute Curie, University Paris, 75005 Paris, France.
⁵ Department of Tumor Biology, Institute Curie, University Paris, 75005 Paris, France.
⁶ Henri Becquerel Cancer Center, Department of Pathology, INSERM U1245, UniRouen Normandy University, 76130 Rouen, France.

Abstract

Introduction: The 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.

Methods: We retrospectively evaluated the 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 three classes (0; 1 to 3; 4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.

Results: 1197 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 (P_interaction = 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).

Conclusion: The 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.

Keywords: breast cancer; neoadjuvant chemotherapy; nodal involvement; number of positive nodes; prognostic; residual axillary disease.