The Role of the Neo-Bioscore Staging System in Guiding the Optimal Strategies for Regional Nodal Irradiation Following Neoadjuvant Treatment in Breast Cancer Patients with cN1 and ypN0–1

  • Lu Cao
  • Cheng Xu
  • Youlia M. Kirova
  • Gang Cai
  • Rong Cai
  • Shu-Bei Wang
  • Kun-Wei Shen
  • Dan Ou
  • Jia-Yi Chen
Breast Oncology



The role of regional nodal irradiation (RNI) in patients with cN1 breast cancer following neoadjuvant treatment (NAT) is still controversial. The Neo-Bioscore staging system has shown promising prospect in assessing individual prognosis after NAT, and we sought to evaluate the role of Neo-Bioscore in guiding RNI following NAT.


Medical records of 163 women with cN1 and ypN0–1 disease treated with NAT between 2009 and 2014 were retrospectively reviewed and a Neo-Bioscore was assigned to each patient. Survivals were calculated using the Kaplan–Meier method and compared with the log-rank test. Multivariate analysis was used to identify independent predictors by using Cox proportional hazards models.


The median follow-up after surgery was 59.4 months. Of all 163 patients, 119 received RNI. At surgery, 36 patients (22.1%) had pathological complete response (pCR), while 89 patients (54.6%) achieved ypN0. In the whole cohort, RNI significantly improved distant metastasis-free survival (DMFS) on multivariable analysis. In the subgroup of patients with a Neo-Bioscore of 1–3, RNI significantly improved the 5-year DMFS rate of 97.0% versus 76.9% (p = 0.002), 5-year regional node recurrence-free survival rate of 95.5% versus 76.9% (p = 0.007), and 5-year overall survival rate of 100% versus 89.2% (p = 0.005). No significant difference in outcomes was found between the RNI and non-RNI groups in patients with a score of 4–6.


In patients with cN1 and ypN0–1, RNI was found to significantly improve DMFS following NAT. Patients with a Neo-Bioscore of 1–3 are more likely to benefit from RNI, however a large prospective study is needed to confirm this finding.



This study was supported in part by the National Natural Science Foundation of China (Grants 81172504, 81673102, and 81602791), National Key Research and Development Program of China (Grant 2016YFC0105409), Youth Foundation of Shanghai Health and Family Planning Commission (Grant 20164Y0066), and Clinical Research Plan of Shanghai Hospital Development Center (Grant 16CR1037B).




  1. 1.
    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer, Version 1. 2018. Accessed 20 Mar 2018.
  2. 2.
    Cao L, Ou D, Shen KW, et al. Outcome of postmastectomy radiotherapy after primary systemic treatment in patients with clinical T1-2N1 breast cancer. Cancer Radiother. 2018;22(1):38–44.CrossRefGoogle Scholar
  3. 3.
    Beriwal S, Shinde A, Rajagopalan MS, Kannan N, Heron DE, Deutsch M. Recommendations for post-mastectomy radiation therapy after neo-adjuvant chemotherapy: an International Survey of Radiation Oncologists. The Breast J. 2013;19(6):683–4.CrossRefGoogle Scholar
  4. 4.
    White J, Mamounas E. Locoregional radiotherapy in patients with breast cancer responding to neoadjuvant chemotherapy: a paradigm for treatment individualization. J Clin Oncol. 2014;32(6):494–5.CrossRefGoogle Scholar
  5. 5.
    Shim SJ, Park W, Huh SJ, 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). Int J Radiat Oncol Biol Phys. 2014;88(1):65–72.CrossRefGoogle Scholar
  6. 6.
    Fowble BL, Einck JP, Kim DN, et al. Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II–III breast cancer. Int J Radiat Oncol Biol Phys. 2012;83(2):494–503.CrossRefGoogle Scholar
  7. 7.
    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;194(7):607–18.CrossRefGoogle Scholar
  8. 8.
    Mittendorf EA, Vila J, Tucker SL, et al. The neo-bioscore update for staging breast cancer treated with neoadjuvant chemotherapy: incorporation of prognostic biologic factors into staging after treatment. JAMA Oncol. 2016;2(7):929–36.CrossRefGoogle Scholar
  9. 9.
    Bergquist JR, Murphy BL, Storlie CB, Habermann EB, Boughey JC. Incorporation of treatment response, tumor grade and receptor status improves staging quality in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2017;24(12):3510–7.CrossRefGoogle Scholar
  10. 10.
    Donovan CA, Giuliano AE. Evolution of the staging system in breast cancer. Ann Surg Oncol. 2017;24(12):3469–70.CrossRefGoogle Scholar
  11. 11.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736–47.CrossRefGoogle Scholar
  12. 12.
    Kestin LL, Sharpe MB, Frazier RC, et al. Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience. Int J Radiat Oncol Biol Phys. 2000;48(5):1559–68.CrossRefGoogle Scholar
  13. 13.
    Radiation Therapy Oncology Group. Breast cancer contouring atlas. Accessed 5 Oct 2018.
  14. 14.
    Cox DR. Regression models and life tables. J R Stat Soc. 1972;34:187–220.Google Scholar
  15. 15.
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81.CrossRefGoogle Scholar
  16. 16.
    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(32):3960–6.CrossRefGoogle Scholar
  17. 17.
    Cao L, Cai G, Xu F, et al. Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy. Medicine (Baltimore). 2016;95(32):e4230.CrossRefGoogle Scholar
  18. 18.
    Mannino M, Yarnold JR. Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever be safely withheld? Radiother Oncol. 2009;90(1):14–22.CrossRefGoogle Scholar
  19. 19.
    Kiess AP, McArthur HL, Mahoney K, et al. Adjuvant trastuzumab reduces locoregional recurrence in women who receive breast-conservation therapy for lymph node-negative, human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2012;118(8):1982–8.CrossRefGoogle Scholar
  20. 20.
    Kyndi M, Overgaard M, Nielsen HM, Sorensen FB, Knudsen H, Overgaard J. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol. 2009;90(1):74–9.CrossRefGoogle Scholar
  21. 21.
    Daveau C, Stevens D, Brain E, et al. 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(2):337–42.CrossRefGoogle Scholar
  22. 22.
    Bae SH, Park W, Huh SJ, et al. Radiation treatment in pathologic n0–n1 patients treated with neoadjuvant chemotherapy followed by surgery for locally advanced breast cancer. J Breast Cancer. 2012;15(3):329–36.CrossRefGoogle Scholar
  23. 23.
    Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–16.CrossRefGoogle Scholar
  24. 24.
    Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373(4):317–27.CrossRefGoogle Scholar
  25. 25.
    Thorsen LB, Offersen BV, Dano H, et al. DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol. 2016;34(4):314–20.CrossRefGoogle Scholar
  26. 26.
    Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–106.CrossRefGoogle Scholar
  27. 27.
    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.CrossRefGoogle Scholar
  28. 28.
    Darby S, McGale P, et al. 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(9804):1707–16.CrossRefGoogle Scholar
  29. 29.
    Stecklein SR, Park M, Liu DD, et al. Long-term impact of regional nodal irradiation in patients with node-positive breast cancer treated with neoadjuvant systemic therapy. Int J Radiat Oncol Biol Phys. 2018;102(3):568–77.CrossRefGoogle Scholar
  30. 30.
    Valachis A, Mamounas EP, Mittendorf EA, et al. Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: an international collaboration and individual patient meta-analysis. Cancer. 2018;124(14):2923–30.CrossRefGoogle Scholar
  31. 31.
    Kyndi M, Sorensen FB, Knudsen H, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26(9):1419–26.CrossRefGoogle Scholar
  32. 32.
    Poortmans P. Postmastectomy radiation in breast cancer with one to three involved lymph nodes: ending the debate. Lancet. 2014;383(9935):2104–6.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Lu Cao
    • 1
    • 2
  • Cheng Xu
    • 2
  • Youlia M. Kirova
    • 3
  • Gang Cai
    • 2
  • Rong Cai
    • 2
  • Shu-Bei Wang
    • 2
  • Kun-Wei Shen
    • 4
  • Dan Ou
    • 2
  • Jia-Yi Chen
    • 2
  1. 1.Shanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  3. 3.Department of Radiation OncologyInstitut CurieParisFrance
  4. 4.Comprehensive Breast Health Center, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina

Personalised recommendations