Abstract
Simple SummaryLittle is known about whether residual axillary disease after neoadjuvant chemotherapy carries a different prognostic value by breast cancer subtype. We retrospectively evaluated the axillary involvement (0, 1 to 3 positive nodes, ≥4 positive nodes) on surgical specimens from a cohort of 1197 patients treated with neoadjuvant chemotherapy, and analyzed its association with survival outcomes. Relapse free survival was significantly associated with the number of positive nodes, but this effect was different by breast cancer subtype (Pinteraction = 0.004). High risk patients were those with 4 or more nodes involved in the luminal subgroup, whereas patients with 1 node or more involved had a decreased prognosis in triple negative and HER2 positive breast cancer subgroups. The prognostic value of residual axillary disease should be interpreted according to breast cancer subtype to accurately stratify patients with a high risk of recurrence after neoadjuvant chemotherapy who should be offered second line therapies.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 (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). 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.
Highlights
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 breast cancers (BC) subtype
Our results show that the prognostic value of the number of post-Neoadjuvant chemotherapy (NAC) positive nodes differs according to BC subtype
Results from our study show that patients with luminal BC presenting post-NAC axillary residual disease up to 3 positive nodes had a similar prognosis to those with no axillary residual disease, while we evidenced a negative impact on survival outcomes when the number of nodes involved was 4 or above
Summary
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. Pathologic complete response (pCR) is defined as the absence of invasive cancer in the breast and axillary lymph nodes, and has been shown to be associated with a better long-term survival among BC patients treated with NAC. Nodal axillary response has been described as a superior prognostic parameter after NAC [12,13], overall pCR is more frequently used and has been adopted by the Food and Drug Administration and the European Medicines Agency as an important endpoint in BC neoadjuvant studies [14]
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