Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05)

J M Noh, W Park, C-O Suh, K C Keum, Y B Kim, K H Shin, K Kim, E K Chie, S W Ha, S S Kim, S D Ahn, H S Shin, J H Kim, H-S Lee, N K Lee, S J Huh, D H Choi, J M Noh, W Park, C-O Suh, K C Keum, Y B Kim, K H Shin, K Kim, E K Chie, S W Ha, S S Kim, S D Ahn, H S Shin, J H Kim, H-S Lee, N K Lee, S J Huh, D H Choi

Abstract

Background: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT).

Methods: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated.

Results: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled.

Conclusions: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Figures

Figure 1
Figure 1
LRRFS (A), DFS (B), and OS (C) according to the ENI. No differences in treatment outcomes were observed.
Figure 2
Figure 2
LRRFS (A), DFS (B), and OS (C) according to pathologic T classification. Disease-free survival and OS were significantly affected by pathologic T classification.

References

    1. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N. 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.
    1. Boughey JC, Donohue JH, Jakub JW, Lohse CM, Degnim AC. Number of lymph nodes identified at axillary dissection: effect of neoadjuvant chemotherapy and other factors. Cancer. 2010;116:3322–3329.
    1. Chen AM, Meric-Bernstam F, Hunt KK, Thames HD, Oswald MJ, Outlaw ED, Strom EA, McNeese MD, Kuerer HM, Ross MI, Singletary SE, Ames FC, Feig BW, Sahin AA, Perkins GH, Schechter NR, Hortobagyi GN, Buchholz TA. Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience. J Clin Oncol. 2004;22:2303–2312.
    1. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–1716.
    1. Daveau C, Stevens D, Brain E, Berges O, Villette S, Moisson P, Gardner M, De la Lande B, Lasry S, Labib A, Le Scodan R. Is regional lymph node irradiation necessary in stage II to III breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2010;78:337–342.
    1. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB, Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. 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. J Clin Oncol. 1997;15:2483–2493.
    1. Fontein DB, van de Water W, Mieog JS, Liefers GJ, van de Velde CJ. Timing of the sentinel lymph node biopsy in breast cancer patients receiving neoadjuvant therapy – recommendations for clinical guidance. Eur J Surg Oncol. 2013;39:417–424.
    1. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–575.
    1. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, Buzdar AU, Smith IE, Symmans WF, Singh B, Winer EP. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814–819.
    1. Haffty BG, Hunt KK, Harris JR, Buchholz TA. Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. J Clin Oncol. 2011;29:4479–4481.
    1. Huang EH, Tucker SL, Strom EA, McNeese MD, Kuerer HM, Buzdar AU, Valero V, Perkins GH, Schechter NR, Hunt KK, Sahin AA, Hortobagyi GN, Buchholz TA. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol. 2004;22:4691–4699.
    1. Lyman GH, Giuliano AE, Somerfield MR, Benson AB, 3rd, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS, 3rd, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–7720.
    1. Mamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB, Geyer CE, Jr, Taghian A, Wickerham DL, Wolmark N. 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.
    1. McGuire SE, Gonzalez-Angulo AM, Huang EH, Tucker SL, Kau SW, Yu TK, Strom EA, Oh JL, Woodward WA, Tereffe W, Hunt KK, Kuerer HM, Sahin AA, Hortobagyi GN, Buchholz TA. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2007;68:1004–1009.
    1. National Comprehensive Cancer Network 2014. NCCN Clinical Practice Guidelines in Oncology; Breast Cancer - v.1, 2014 [cited 2013 December 29]. Available from .
    1. Neuman H, Carey LA, Ollila DW, Livasy C, Calvo BF, Meyer AA, Kim HJ, Meyers MO, Dees EC, Collichio FA, Sartor CI, Moore DT, Sawyer LR, Frank J, Klauber-DeMore N. Axillary lymph node count is lower after neoadjuvant chemotherapy. Am J Surg. 2006;191:827–829.
    1. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337:949–955.
    1. Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, Knowling MA, Coppin CM, Weir L, Gelmon K, Le N, Durand R, Coldman AJ, Manji M. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97:116–126.
    1. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–785.
    1. Reznik J, Cicchetti MG, Degaspe B, Fitzgerald TJ. Analysis of axillary coverage during tangential radiation therapy to the breast. Int J Radiat Oncol Biol Phys. 2005;61:163–168.
    1. Shim SJ, Park W, Huh SJ, Choi DH, Shin KH, Lee NK, Suh CO, Keum KC, Kim YB, Ahn SD, Kim SS, Ha SW, Chie EK, Kim K, Shin HS, Kim JH, Lee HS. 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) Int J Radiat Oncol Biol Phys. 2014;88:65–72.
    1. Weir L, Speers C, D'Yachkova Y, Olivotto IA. Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer. J Clin Oncol. 2002;20:1793–1799.

Source: PubMed

3
Sottoscrivi