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Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis

      Highlights

      • Intensified therapies predominated for surgery, chemotherapy, and radiotherapy.
      • Locoregional radiotherapy was associated with improved outcomes, and notably for improved locoregional relapse-free survival in triple-negative breast cancer.
      • Locoregional radiotherapy omission was a factor predicting lower breast cancer-specific survival and overall survival on multivariable analysis.

      Abstract

      Background

      Data guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment.

      Materials and Methods

      There were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS).

      Results

      Median follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes.

      Conclusion

      In this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.

      Keywords

      Abbreviations:

      RT (radiotherapy), NAC (neoadjuvant chemotherapy), LRRT (locoregional radiotherapy), LRRFS (locoregional relapse-free survival), BCSS (breast cancer specific survival), OS (overall survival), TNBC (triple negative breast cancer), pCR (pathologic complete response), BCS (breast conserving surgery), SNB (sentinel node biopsy), AND (axillary nodal dissection)
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