Abstract P3-18-03: Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC)
Authors: Wang Kang , Duinmeijer Aafke , Matikas Alexios , Altena Renske , Johansson Hemming , Fredholm Hanna , Foukakis Theodoros 
Published: March 2022

Abstract
Background: Population-based studies have consistently shown improved long-term outcomes with breast conserving surgery (BCS) plus radiotherapy (RT) vs. mastectomy in primarily operated breast cancer (BC) patients. However, the survival impact of type of local therapy following modern neoadjuvant systemic therapy (NST) is unclear. Methods: The population-based Swedish National Breast Cancer Register (NKBC), a prospectively collected population-based cohort, was used to identify female BC patients who were diagnosed from January, 2007 until December, 2017 and received NST in the Stockholm region. Patients were divided into BCS+RT and mastectomy groups, and the prognostic factors reflecting the response to NST like pathologic complete response (pCR) and Neo-bioscore calculated by pre/postoperative TNM stage, nuclear grade, and receptors status, were used for stratification. Disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using inverse probability of treatment weighted (IPTW) Cox proportional hazards model, which enables covariates like age, St Gallen subtypes, cTNM and ypTNM stages to be balanced between the two groups. Results: Among 1,409 eligible women, 456 (32.4%) were treated with BCS+RT, and 953 (67.6%) with mastectomy. Overall, 87 (6.2%) local recurrences, 256 (18.2%) distant metastases, and 282 (20.0%) deaths occurred over a median follow-up of 61 months. Patients diagnosed during later years, younger patients, patients with earlier stage and higher-grade tumors were more likely to receive BCS+RT. After adjusting for age at diagnosis, Neo-bioscore, adjuvant chemotherapy and radiotherapy, significant improvements for BCS+RT compared with mastectomy were observed in DFS (weighted-multivariate hazard ratio (HR), 0.51; 95%CI, 0.28-0.93; median 5-year DFS: 79.1% vs 73.6%) and DMFS (HR, 0.44; 95%CI, 0.23-0.82; median 5-year DMFS: 83.7% vs 74.8%), but no difference was identified in LRFS (HR, 0.94; 95%CI, 0.29-3.07; median 5-year LRFS: 89.9% vs 92.0%) or OS (HR, 0.7; 95%CI, 0.34-1.45; median 5-year OS: 88.4% vs 81.2%). The DFS benefit was observed regardless of pCR status, but varied by Neo-bioscore. Patients with Neo-bioscore 4-7 treated with BCS+RT had better DFS (HR, 0.31; 95%CI, 0.12-0.81) compared with those undergoing mastectomy, whereas low-risk patients with Neo-bioscore 0-3 had similar DFS between the two groups. Both triple negative (N=252; HR for DFS, 0.26; 95%CI, 0.07-0.97) and HER2-positive (N=533; HR for DFS, 0.24, 95%CI, 0.09-0.68) BC patients benefited from BCS+RT, but not patients with luminal tumors (N=589; HR for DFS, 0.82, 95%CI, 0.31-2.18). Similarly, superior DFS with BCS+RT was also seen in patients with neoadjuvant anti-HER2 targeted therapy (N=505; HR, 0.19; 95%CI, 0.05-0.75) or neoadjuvant chemotherapy alone (N=594; HR, 0.47; 95%CI, 0.21-1.06), but not among those receiving neoadjuvant endocrine therapy (N=162; HR, 0.53; 95%CI, 0. 1-2.85). Conclusion: After adjusting for response to NST and other confounders, BCS+RT was associated with reduced risks of tumor recurrence or metastasis compared with mastectomy. This benefit was more pronounced in patients with high Neo-bioscore, indicating that Neo-bioscore rather than pCR status has the potential to tailor breast surgery after NST. Further studies with larger sample size or prospective randomized clinical trials are warranted to confirm our findings.
Citation Format: Kang Wang, Aafke Duinmeijer, Alexios Matikas, Renske Altena, Hemming Johansson, Hanna Fredholm, Theodoros Foukakis. Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-03.