Axillary surgery efficacy for patients with breast cancer receiving neoadjuvant chemotherapy on NSABP B40 and B41.
Authors: Mailhot Vega Raymond , Deladisma Adeline M. , Mobley Erin Michele , Wang Shu , Morris Christopher G. , Oladeru Oluwadamilola Temilade , Brooks Eric , Gharia Bharatsinh M. , Spiguel Lisa R. , MacDonald Shannon M. , Mamounas Eleftherios P. , Mendenhall Nancy P. , Okunieff Paul G. , Lee Ji-Hyun , Neumayer Leigh A. , Bradley Julie Ann 
Published: June 2023

524 Background: Alliance A011202 is evaluating the efficacy of axillary lymph node dissection (ALND) compared to regional nodal irradiation (RNI) for patients with cN1 breast cancer who receive neoadjuvant chemotherapy (NCTX) that becomes ycN0 but remains pN+. In the absence of its publication, level I guidance does not exist regarding the optimal axillary surgery for patients receiving NCTX. We sought to evaluate outcomes across two national contemporary clinical NCTX trials based on axillary and breast response to NCTX, particularly if more aggressive surgery was associated with more favorable outcomes. Methods: With IRB approval (IRB201802781), we obtained data from NCTX trials NSABP B40 and B41. B40 enrolled women with HER2- disease, and B41 enrolled those with HER2+ disease. RNI and axillary surgery were selected at physician discretion and not protocolled. Patients received sentinel lymph node biopsy (SLNB), SLNB+ALND (S+ALND), or ALND. We examined outcomes of locoregional recurrence (LRR), distant recurrence (DR), disease free survival (DFS), and overall survival (OS). Univariable and multivariable analyses of B40 and B41 data were performed to evaluate the associations of axillary surgery with the outcomes above, adjusting for age, tumor subtype, mastectomy or not, breast pathologic complete response (pCR), axillary pCR, tumor subtype, regional nodal irradiation, and grade. Kaplan-Meier estimation was used for OS and DFS, with cumulative incidence function for LRR and DR. Results: Median follow-up for studies B40 and B41 were 4.5 and 5.1 years, respectively, including 1154 and 504 patients for analysis. A total of 786 (47%) patients were cN+, and of those, 377 had a pcR (48%). 440 (27%), 505 (31%), and 663 (41%) patients had SLNB, S+ALND, and ALND respectively. 855 (52%) and 803 (48%) patients had mastectomy and lumpectomy, respectively. 783 (51%) received RNI. For the 518 ypN+ patients on B40, 7/25 (SLNB), 69/234 (S+ALND), and 107/259 (ALND) experienced an event. DFS at 5 years was 71%, 68%, and 56% for the SLNB, S+ALND, and ALND groups respectively with ypN+ on B40. For the 112 ypN+ patients on B41, 3/6, 15/43, and 27/63 experienced an event. DFS at 5 years was 50%, 64%, and 55% for the SLNB, S+ALND, and ALND groups, respectively, with ypN+ on B41. In multivariable analyses for the combined population of B40 and B41 for LRR, DR, DFS, and OS, SLNB was never associated with a higher chance of relapse or inferior survival (HR > 1) compared to S+ALND or ALND. Conclusions: Among women prospectively treated on national trials with NCTX and axillary surgery and RNI selected at physician discretion, receipt of SLNB alone was not associated with a higher likelihood of recurrence compared to S+ALND or ALND. Anticipated results of A011202 will provide level I guidance on axillary surgery for patients with cN1 disease converting to cN0 post-NCTX.