Post-Mastectomy Radiotherapy After Neoadjuvant Chemotherapy in Breast Cancer: A Pooled Retrospective Analysis of Three Prospective Randomized Trials
- 103 Downloads
The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy.
A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%).
The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0–22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7–14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27–1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis.
Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.
The authors thank all participating centers for providing radiotherapy reports. This work was previously presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, USA, 29 May–2 June 2015.
Financial support for the original trials was provided by Amgen, Chugai, GlaxoSmithKline, Roche, and Sanofi-Aventis.
David Krug, Bianca Lederer, Fenja Seither, Valentina Nekljudova, Beyhan Ataseven, Jens-Uwe Blohmer, Serban Dan Costa, Carsten Denkert, Nina Ditsch, Bernd Gerber, Claus Hanusch, Joerg Heil, Jörn Hilfrich, Jens B. Huober, Christian Jackisch, Sherko Kümmel, Stefan Paepke, Christian Schem, Andreas Schneeweiss, Michael Untch, Jürgen Debus, Gunter von Minckwitz, Thorsten Kühn, and Sibylle Loibl have no conflicts of interest relevant to this study.
- 13.Huober J, Fasching PA, Hanusch C, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with non-responsive tumours to epirubicin/cyclophosphamide (EC) ± bevacizumab—results of the randomised GeparQuinto study (GBG 44). Eur J Cancer. 2013;49(10):2284–293.CrossRefGoogle Scholar
- 20.EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale P, Taylor C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935):2127–35.Google Scholar
- 21.Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39.Google Scholar
- 23.Garg AK, Strom EA, McNeese MD, et al. T3 disease at presentation or pathologic involvement of four or more lymph nodes predict for locoregional recurrence in stage II breast cancer treated with neoadjuvant chemotherapy and mastectomy without radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(1):138–45.CrossRefGoogle Scholar
- 27.Krug D, Baumann R, Budach W, et al. Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer: a systematic review. Strahlenther Onkol. 2018;21:2600–12.Google Scholar