Mutlay SAYAN, Irina VERGALASOVA, Mridula GEORGE, Maria KOWZUN, Lindsay POTDEVIN, Shicha KUMAR, Bruce HAFFTY, Nisha OHRI

Patterns of postmastectomy radiation therapy in clinically node-positive breast cancer patients with pathologically negative lymph nodes after neoadjuvant chemotherapy

Background/aim: To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node-positive breast cancer who are pathologically node-negative (ypN0) after neoadjuvant chemotherapy (NAC). Materials and methods: Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive nonmetastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. Results: The study included 8766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and a greater number of lymph nodes examined. The unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p = NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). Conclusion: The delivery of PMRT has increased over time in women presenting with clinically node-positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

PDF

___

1. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. New England Journal of Medicine 1997; 337 (14): 949-955. doi: 10.1056/NEJM199710023371401
2. Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999; 353 (9165): 1641-1648. doi: 10.1016/S0140- 6736(98)09201-0
3. McGale P, Taylor C, Correa C, Cutter D, Duane F 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): 2127-2135. doi: 10.1016/S0140- 6736(14)60488-8
4. Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ et al. NRG Oncology/NSABP B-51/RTOG 1304: Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to whole breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCR-FI) in patients (pts) with pathologically positive axillary (PPAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC). Journal of Clinical Oncology 2019; 37 (15): 600-600. doi: 10.1200/JCO.2019.37.15_suppl.TPS600
5. Mamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB 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. Journal of Clinical Oncology 2012; 30 (32): 3960-3966. doi: 10.1200/JCO.2011.40.8369
6. Huang EH, Tucker SL, Strom EA, McNeese MD, Kuerer HM et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. Journal of Clinical Oncology 2004; 22 (23): 4691- 4699. doi: 10.1200/JCO.2004.11.129
7. Buchholz TA, Tucker SL, Masullo L, Kuerer HM, Erwin J et al. Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. Journal of Clinical Oncology 2002; 20 (1): 17-23. doi: 10.1200/ JCO.2002.20.1.17
8. Wright JL, Takita C, Reis IM, Zhao W, Saigal K et al. Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation. Cancer 2013; 119 (1): 16-25. doi: 10.1002/cncr.27717
9. Mougalian SS, Soulos PR, Killelea BK, Lannin DR, Abu-Khalaf MM et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer 2015; 121 (15): 2544-2552. doi: 10.1002/cncr.29348
10. Bonadonna G, Veronesi U, Brambilla C, Ferrari L, Luini A et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. Journal of the National Cancer Institute 1990; 82 (19): 1539-1545. doi: 10.1093/ jnci/82.19.1539
11. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. Journal of Clinical Oncology 1997; 15 (7): 2483-2493. doi: 10.1200/ JCO.1997.15.7.2483
12. Shim SJ, Park W, Huh SJ, Choi DH, Shin KH et al. The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). International Journal of Radiation Oncology Biology Physics 2014; 88 (1): 65-72. doi: 10.1016/j.ijrobp.2013.09.021
13. Le Scodan R, Selz J, Stevens D, Bollet MA, De La Lande B et al. Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. International Journal of Radiation Oncology Biology Physics 2012; 82 (1): 1-7. doi: 10.1016/j. ijrobp.2010.12.054
14. McGuire SE, Gonzalez-Angulo AM, Huang EH, Tucker SL, Kau SC et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. International Journal of Radiation Oncology Biology Physics 2007; 68 (4): 1004-1009. doi: 10.1016/j.ijrobp.2007.01.023
15. Whelan TJ, Olivotto I, Ackerman JW, Chapman JW, Chua B et al. NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer. Journal of Clinical Oncology 2011; 29 (18): 1003-1003. doi:10.1200/jco.2011.29.18_suppl. lba1003
16. Poortmans P, Fourquet A, Collette L, Struikmans H, Bartelink H et al. Irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer: state of the day of EORTC phase III trial 22922/10925 with 4004 patients. European Journal of Cancer Supplements 2010; 8 (3): 54. doi: https://doi.org/10.1016/S1359-6349(10)70033-1