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Regional Nodal Irradiation for Clinically Node-Positive Breast Cancer Patients With Pathologic Negative Nodes After Neoadjuvant Chemotherapy

      Abstract

      Introduction

      Neoadjuvant chemotherapy (NAC) is increasingly used for operable breast cancer (BC). Appropriate radiation therapy (RT) fields (ie, whole breast [WB] ± regional nodal irradiation [RNI]) in patients who were clinically node positive (cN1) but convert to pathologically node negative (ypN0) after NAC are unknown and the subject of the accruing NSABP B-51 trial. We sought to compare outcomes between WB RT with or without RNI following breast conservation and sentinel lymph node biopsy (SLNB) alone in cN1, ypN0 women following NAC.

      Patients and Methods

      We identified all BC patients with cN1, ypN0 who underwent NAC followed by lumpectomy and SLNB between 2006 and 2015 in the National Cancer Database. RNI utilization was evaluated using Cochran-Armitage test. Overall survival between WB RT alone versus WB + RNI was compared using Kaplan-Meier with and without propensity score-based weighted adjustment and multivariable (MVA) Cox proportional hazards.

      Results

      From 2006 to 2015, RNI use increased from 48.13% to 62.13% (Pfor trend <.001). The 10-year survival for WB alone versus WB + RNI was 83.6% and 79.5%, respectively (P= .14). On MVA analysis, the addition of RNI compared to WB alone was not associated with a survival benefit (WB vs. WB + RNI: hazard ratio 0.80, 95% confidence interval, 0.58-1.11, P= .19). Results were unchanged after propensity score-based adjustment.

      Conclusion

      For women with cN1 BC who convert to ypN0 following NAC and breast conserving surgery with SLNB alone, more extensive RNI may not provide a long-term survival benefit. Prospective validation via the NSABP B-51 trial will be essential.

      Keywords

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      References

        • Bear HD
        • Anderson S
        • Brown A
        • et al.
        The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.
        J Clin Oncol. 2003; 21: 4165-4174
        • Fisher B
        • Brown A
        • Mamounas E
        • et al.
        Effect of preoperative chemotherapy on loco-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.
        J Clin Oncol. 1997; 15: 2483-2493
        • Golshan M
        • Cirrincione CT
        • Silkov VM
        • et al.
        Alliance for clinical trials in oncology. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).
        Ann Surg. 2015; 262: 434-439
        • Mamounas EP
        • Brown A
        • Anderson S
        • et al.
        Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.
        J Clin Oncol. 2005; 23: 2694-2702
        • Masuda N.
        • Lee S.J.
        • Ohtani S.
        • et al.
        Adjuvant capecitabine for breast cancer after preoperative chemotherapy.
        N Engl J Med. 2017; 376: 2147-2159
        • Gradishar WJ
        • Anderson BO
        • Abraham J
        • et al.
        Breast cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.
        J Natl Compr Canc Netw. 2020; 18(4): 452-478
        • Whelan TJ
        • Olivotto IA
        • Parulekar WR
        • et al.
        Regional nodal irradiation in early-stage breast cancer.
        N Engl J Med,. 2015; 373: 307-316
        • Poortmans PM
        • Collette S
        • Kirkove C
        • et al.
        Internal mammary and medial supraclavicular irradiation in breast cancer.
        N Engl J Med. 2015; 373: 317-327
        • Mamounas EP
        • Anderson SJ
        • Dignam JJ
        • et al.
        Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27.
        J Clin Oncol. 2012; 30: 3960-3966
        • Bilimoria KY
        • Stewart AK
        • Winchester DP
        • Ko CY.
        The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
        Ann Surg Oncol. 2008; 15: 683-690
        • Kantor O
        • Pesce C
        • Liederbach E
        • Wang CH
        • Winchester DJ
        • Yao K.
        Are the ACOSOG Z0011 Trial findings being applied to breast cancer patients undergoing neoadjuvant chemotherapy?.
        Breast J. 2017; 23: 554-562
        • Kuehn T
        • Bauerfeind
        • Fehm T
        • et al.
        Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicenter cohort study.
        Lancet Oncol. 2013; 14: 609-618
        • Boughey JC
        • Suman VJ
        • Miitendorf EA
        • et al.
        Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.
        JAMA. 2013; 310: 1455-1461
        • Budach W
        • Bolke E
        • Kammers K
        • Gerber PA
        • Nestle-Kramling C
        • Matuschek C.
        Adjuvant radiation therapy of regional lymph nodes in breast cancer – a meta-analysis of randomized trials- an update.
        Radiat Oncol. 2015; 10: 258
        • Dodwell D
        • Taylor C
        • McGale P
        • et al.
        Abstract GS4-02: regional lymph node irradiation in early stage breast cancer: an EBCTCG meta-analysis of 13,000 women in 14 trials.
        Cancer Res. 2019; 79: GS4-G02https://doi.org/10.1158/1538-7445.SABCS18-GS4-02
        • Darby SC
        • Ewertz M
        • McGale P
        • et al.
        Risk of ischemic heart disease in women after radiotherapy for breast cancer.
        N Engl J Med. 2013; 368: 987-998
        • Wang D
        • Yang X
        • He J
        • et al.
        Impact of regional nodal irradiation and hypofractionated whole-breast radiation on long-term breast retraction and poor cosmetic outcome in breast cancer survivors.
        Clin Breast Cancer. 2020; 20: e75-e81
        • Rusthoven CG
        • Rabinovitch RA
        • Jones BL
        • et al.
        The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis.
        Ann Oncol. 2016; 27: 818-827
        • Boughey JC
        • Suman VJ
        • Mitterndorf EA
        • et al.
        Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance).
        Ann Surg. 2015; 261: 547-552
        • Boughey JC
        • Ballman KV
        • Le-Petross HT
        • et al.
        Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance).
        Ann Surg. 2016; 263: 802-807
        • Caudle AS
        • Yang WT
        • Krishnamurthy S
        • et al.
        Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection.
        J Clin Oncol. 2016; 34: 1072-1078
        • Wong SM
        • Basik M
        • Florianova L
        • et al.
        Oncologic safety of sentinel lymph node biopsy alone after neoadjuvant chemotherapy for breast cancer.
        Ann Surg Oncol. 2021; 28(5): 2621-2629
        • Kahler-Ribeiro-Fontana S
        • Pagan E
        • Magnoni F
        • et al.
        Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.
        Eur J Surg Oncol. 2021; 47: 804-812
        • Luo J
        • Jin K
        • Chen X
        • et al.
        Internal mammary node irradiation (IMNI) improves survival outcome for patients with clinical stage II-III breast cancer after preoperative systemic therapy.
        Int J Radiat Oncol Biol Phys. 2019; 103: 895-904
        • Kim KH
        • Noh JM
        • Kim YB
        • et al.
        Does internal mammary node irradiation affect treatment outcome in clinical stage II-III breast cancer patients receiving neoadjuvant chemotherapy?.
        Breast Cancer Res Treat. 2015; 152: 589-599
        • McGale P
        • Cutter D
        • Darby SC
        • Henson KE
        • Jagsi R
        • Taylor CW.
        Can observational data replace randomized trials?.
        J Clin Oncol. 2016; 34: 3355-3357