Skip to main content

Advertisement

SpringerLink
Log in

The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

A Correction to this article was published on 26 February 2021

This article has been updated

Abstract

Background

The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype.

Patients and Methods

We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups.

Results

A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2−/HR+), HER2-positive (HER2+)/HR+, and HER2−/HR-negative (HR−) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034–0.379; p < 0.001), 0.159 (95% CI 0.038–0.671; p = 0.017), and 0.243 (95% CI 0.088–0.676; p = 0.007), respectively, but not for the HER2+/HR− subtype (p = 0.468).

Conclusions

We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3

Similar content being viewed by others

Change history

References

  1. Overgaard M, Hansen PS, Overgaard J, et al. 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(14):949–55.

  2. Overgaard M, Jensen MB, Overgaard J, 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):1641–48.

    Article  CAS  Google Scholar 

  3. McGale P, Taylor C, Correa 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.

    Article  CAS  Google Scholar 

  4. Mougalian SS, Soulos PR, Killelea BK, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015;121(15):2544–52.

    Article  Google Scholar 

  5. Huang EH, Tucker SL, Strom EA, et al. 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(23):4691–99.

    Article  Google Scholar 

  6. Miyashita M, Niikura N, Kumamaru H, et al. Role of postmastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer patients: a study from the Japanese breast cancer registry. Ann Surg Oncol. 2019;26(8):2475–85.

    Article  Google Scholar 

  7. McGuire SE, Gonzalez-Angulo AM, Huang EH, et al. 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(4):1004–9.

    Article  Google Scholar 

  8. Meattini I, Cecchini S, Di Cataldo V, et al. Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy. Biomed Res Int. 2014;2014:719175.

    Article  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. Krug D, Lederer B, Seither F, et al. Post-mastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer: a pooled retrospective analysis of three prospective randomized trials. Ann Surg Oncol. 2019;26(12):3892–901.

    Article  Google Scholar 

  11. 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(5):818–27.

    Article  CAS  Google Scholar 

  12. Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J. 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.

    Article  CAS  Google Scholar 

  13. Tseng YD, Uno H, Hughes ME, et al. Biological subtype predicts risk of locoregional recurrence after mastectomy and impact of postmastectomy radiation in a large national database. Int J Radiat Oncol Biol Phys. 2015;93(3):622–30.

    Article  Google Scholar 

  14. Scheer AS, Zih FS, Maki E, Koch CA, McCready DR. Post-mastectomy radiation: should subtype factor into the decision? Ann Surg Oncol. 2016;23(8):2462–70.

    Article  Google Scholar 

  15. Laurberg T, Tramm T, Nielsen T, et al. Intrinsic subtypes and benefit from postmastectomy radiotherapy in node-positive premenopausal breast cancer patients who received adjuvant chemotherapy – results from two independent randomized trials. Acta Oncol. 2018;57(1):38–43.

    Article  Google Scholar 

  16. Cho WK, Park W, Choi DH, et al. The benefit of post-mastectomy radiotherapy in ypN0 patients after neoadjuvant chemotherapy according to molecular subtypes. J Breast Cancer. 2019;22(2):285–96.

    Article  Google Scholar 

  17. Balachandran VP, Gonen M, Smith JJ, DeMatteo RP. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015;16(4):e173-180.

    Article  Google Scholar 

  18. Albert JM, Liu DD, Shen Y, et al. Nomogram to predict the benefit of radiation for older patients with breast cancer treated with conservative surgery. J Clin Oncol. 2012;30(23):2837–43.

    Article  Google Scholar 

  19. Luo C, Zhong X, Deng L, Xie Y, Hu K, Zheng H. Nomogram predicting locoregional recurrence to assist decision-making of postmastectomy radiation therapy in patients with T1-2N1 breast cancer. Int J Radiat Oncol Biol Phys. 2019;103(4):905–12.

    Article  Google Scholar 

  20. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.

    Article  CAS  Google Scholar 

  21. Frati A, Chereau E, Coutant C, et al. Comparison of two nomograms to predict pathologic complete responses to neoadjuvant chemotherapy for breast cancer: evidence that HER2-positive tumors need specific predictors. Breast Cancer Res Treat. 2012;132(2):601–7.

    Article  CAS  Google Scholar 

  22. Buchholz TA, Tucker SL, Masullo L, et al. Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. J Clin Oncol. 2002;20(1):17–23.

    Article  CAS  Google Scholar 

  23. Wang X, Xu L, Yin Z, et al. Locoregional recurrence-associated factors and risk-adapted postmastectomy radiotherapy for breast cancer staged in cT1-2N0-1 after neoadjuvant chemotherapy. Cancer Manag Res. 2018;10:4105–12.

    Article  Google Scholar 

  24. Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS. Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst. 2005;97(6):419–24.

    Article  Google Scholar 

  25. 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(11):987–98.

    Article  CAS  Google Scholar 

  26. Ohri N, Moshier E, Ho A, et al. Postmastectomy radiation in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy: usage rates and survival trends. Int J Radiat Oncol Biol Phys. 2017;99(3):549–59.

    Article  Google Scholar 

  27. He L, Lv Y, Song Y, Zhang B. The prognosis comparison of different molecular subtypes of breast tumors after radiotherapy and the intrinsic reasons for their distinct radiosensitivity. Cancer Manag Res. 2019;11:5765–75.

    Article  CAS  Google Scholar 

  28. Schmidberger H, Hermann RM, Hess CF, Emons G. Interactions between radiation and endocrine therapy in breast cancer. Endocr Relat Cancer. 2003;10(3):375–88.

    Article  CAS  Google Scholar 

  29. Sinclair WK, Morton RA. X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells. Radiat Res. 1966;29(3):450–74.

    Article  CAS  Google Scholar 

  30. Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res. 1999;59(6):1347–55.

    CAS  PubMed  Google Scholar 

  31. O’Rorke MA, Murray LJ, Brand JS, Bhoo-Pathy N. The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: A systematic review and meta-analysis of 5507 patients. Cancer Treat Rev. 2016;47:12–21.

    Article  Google Scholar 

Download references

Funding

This work was supported by the National Key Development Plan for Precision Medicine Research (Grant Number 2017YFC0910004); the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant Number ZYGD18012); and the Key Research and Development Project of Sichuan Province of China (grant number 2018SZ0021).

Author information

Author notes

  1. Jia-Chun Ma, Xiao-Rong Zhong and Ting Luo had equal contribution to this work

Authors and Affiliations

  1. Department of Head and Neck Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Jia-Chun Ma MB, Zhong-Zheng Xiang MM, Fang Liu MM & Lei Liu MD

  2. Department of Head, Neck and Mammary Gland Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China

    Xiao-Rong Zhong MD, Ting Luo MD, Chuanxu Luo MD, Xi Yan MM, Ping He MB, Ting-Lun Tian MB & Hong Zheng MD

  3. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, China

    Jia-Yuan Li MD

Authors
  1. Jia-Chun Ma MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Rong Zhong MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ting Luo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhong-Zheng Xiang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia-Yuan Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chuanxu Luo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xi Yan MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ping He MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ting-Lun Tian MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fang Liu MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lei Liu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hong Zheng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lei Liu MD.

Ethics declarations

Disclosure

Jia-Chun Ma, Xiao-Rong Zhong, Ting Luo, Zhong-Zheng Xiang, Jia-Yuan Li, Chuanxu Luo, Xi Yan, Ping He, Ting-Lun Tian, Fang Liu, Lei Liu, and Hong Zheng have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: Xiao-Rong Zhong’s given name was incorrect.

Supplementary Information

Below is the link to the electronic supplementary material.

Figure S1. Calibration curves of the nomogram to predict LRR in the No-PMRT group

Figure S2. Calibration curves of the nomogram to predict LRR in the external validation group

Figure S3. X-tile analysis of the effect of the nomogram score for local recurrence in unirradiated patients

Figure S4. Kaplan-Meier probability plots of LRR, DR and BCM by PMRT for all patients (A-C), patients in the low-risk group (D-F) and patients in the high-risk group (G-I) (PDF 622 kb)

Supplementary material 2 (DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, JC., Zhong, XR., Luo, T. et al. The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype. Ann Surg Oncol 28, 5084–5095 (2021). https://doi.org/10.1245/s10434-020-09523-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-09523-1

Search

Navigation