Abstract

Abstract BACKGROUND Neoadjuvant chemotherapy (NAC) plays a crucial role in breast cancer treatment. Besides having prognostic relevance, this downstaging allows for more conservative breast surgery, now the standard of practice. This strategy of de-escalation in axillary surgery after NAC is less stablished, especially in cN+ that turn into ycN0 tumors, where axillary lymph node dissection (ALND) or targeted ALND (TAD) with previous referencing of metastatic lymph combined with sentinel lymph node biopsy (SLNB) are options. Assuming that nodal complete pathologic response (pCR) after NAC is dependent of tumor biology, we intent to identify molecular subtypes or biological factors associated with nodal pCR, and so identify which ones are the potential candidates for a more conservative axillary approach, such as SLNB. METHODS From 1st January of 2017 to 31st December of 2021, all patients with cN+, ypN+(sn) and cT4Nx invasive breast cancer, who were submitted to ALND after NAC at our center, were retrospectively evaluated. Nodal pCR defined by absence of axillary invasive disease. RESULTS 591 patients were submitted to ALND after NAC during this 5-year period. Clinicopathological characteristics are described in table 1. Overall nodal pCR rate was 39.8%. The greatest nodal pCR rate occurred in the Her2 type (66.2%), following luminal B Her2+ (56.4%), TN (54%) and at least luminal B Her2- (27.2%) and luminal A (20.5%) tumors - p < 0.001. On univariate analysis, the subtypes Her2type (OR 3.400, 95%CI 1.974-5.855, p< 0.001), luminal BHer2+ (OR 2.237, 95%CI 1.431-3.497, p< 0.001) and TN (OR 2.011, 95%CI 1.303-3.103, p 0.002) are all associated with higher rates of nodal pCR. On the other hand, luminal A (OR 0.346, 95%CI 0.195-0.617, p< 0.001) and luminal B Her2- subtypes (OR 0.384, 95%CI 0.271-0.545, p< 0.001) are associated with less nodal pCR. Ki67 (OR 1.027, 95%CI 1.020-1.035, p< 0.001) and tumoral pCR (OR 13.688, 95%CI 8.693-21.552, p< 0.001) are also associated with higher rates of nodal pCR. On multivariate analysis, the subtypes Her2type and Luminal B Her2+ remain independently associated with nodal pCR – OR 2.417, 95%CI 1.078-5.549, p 0.032 and OR 2.080, 95%CI 1.005-4.304, p 0.049, respectively – as well as Ki67% (OR 1.019, 95%CI 1.009-1.030, p< 0.001) and tumoral pCR (OR 9.425, 95%CI 5.750-15.449, p< 0.001). When considering Ki67, TN tumors with Ki67≥50% are also identified as an independently associated factor with pCR – OR 4.946, 95%CI 1.190-20.559, p 0.028. DISCUSSION AND CONCLUSION The overall nodal pCR after NAC is around 40% and it clearly differs between molecular subtypes, being superior in the Her2type (66.2%), luminal B Her2+ (56.4%) and TN (54%) and at least 2 times inferior in luminal A (20.5%) and B Her2- tumors (27.2%). Data reveal Her2 expression (Her2type and luminal B Her2+) as an independent factor associated with higher nodal pCR rates, as well as the Ki67% and the tumoral pCR, consistent with tumor biology. In this series, the remaining molecular subtypes do not correlate in a consistent way with nodal pCR, but there’s a trend for luminal A and B Her2- to influence it negatively, as opposed to TN, which appears to influence it positively. Besides that, the subgroup of TN tumors with high proliferative rates (Ki67≥50%,) appears to correlate with nodal pCR on multivariate analysis. Parallel to tumoral pCR, nodal pCR can represent a chance to make axillary surgery more conservative. ALDN has a relevant morbidity and TAD, although less aggressive, requires a series of technical procedures that are usually difficult to perform in hospital facilities due to logistic constraints. Recognizing the subtypes which have more consistent nodal pCR, the so-called “good responders”, can help to identify which ones are the potential candidates for a more conservative approach, as is SLNB. In this study, Her2+ tumors and eventually TN with high Ki67, appear as those with greater consistency in nodal pCR, being possible targets for this strategy. Potential Candidates for Conservative Axillary Surgery after Neoadjuvant Chemotherapy Table 1 - Clinicopathological characteristics Citation Format: Beatriz Pereira Gonçalves, Beatriz Costeira, Cátia Fernandes da Cunha, Rodrigo Oom, Cristina Costa, João Vargas Moniz, Nuno Abecasis, Catarina Rodrigues dos Santos. Potential Candidates for Conservative Axillary Surgery after Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-03.

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