Skip to main content

Advertisement

Log in

Concurrent administration of trastuzumab with locoregional breast radiotherapy: long-term results of a prospective study

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55 %. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0–126.0). Median age at diagnosis was 52 years (25–83). Internal mammary node (IMN) RT was performed in 227 patients (73.7 %). After completion of RT, 26 patients (8.4 %) presented an impaired LVEF: 17 (5.5 %) of grade 1, 7 (2.3 %) of grade 2, and 2 (0.6 %) of grade 3. At 48 months, locoregional control rate was 95 % [95 % CI 92; 98], and overall survival rate was 98 % [95 % CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Spector NL, Blackwell KL (2009) Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor-2 positive breast cancer. J Clin Oncol 27:5838–5847

    Article  CAS  PubMed  Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  CAS  PubMed  Google Scholar 

  3. Voduc KD, Cheang MC, Tyldesley S et al (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691

    Article  PubMed  Google Scholar 

  4. Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

  5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    Article  CAS  PubMed  Google Scholar 

  6. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684

    Article  CAS  PubMed  Google Scholar 

  7. Clarke M, Collins R, Darby S et al (2005) 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 366:2087–2106

    Article  CAS  PubMed  Google Scholar 

  8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Darby S, Mc Gale P et al (2011) Effect of radiotherapy after breast-conserving surgery on 10 year recurrence and 15 year breast cancer death: meta-analysis on individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716

    Article  Google Scholar 

  9. Pietras RJ, Poen JC, Gallardo D et al (1999) Monoclonal antibody to HER-2/neu receptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 59:1347–1355

    CAS  PubMed  Google Scholar 

  10. Belkacémi Y, Gligorov J, Ozsahin M et al (2008) Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. Ann Oncol 19:1110–1116

    Article  PubMed  Google Scholar 

  11. Shaffer R, Tyldesley S, Rolles M et al (2009) Acute cardiotoxicity with concurrent trastuzumab and radiotherapy including internal mammary chain nodes: a retrospective single-institution study. Radiother Oncol 90:122–126

    Article  CAS  PubMed  Google Scholar 

  12. Bellon JR, Gover MT, Burstein HJ et al (2005) Concurrent trastuzumab and radiation therapy (RT) in the adjuvant treatment of breast cancer. Int J Radiat Oncol Biol Phys 63(Suppl 1):S55–S56

    Article  Google Scholar 

  13. Meattini I, Cecchini S, Muntoni C et al (2014) Cutaneous and cardiac toxicity of concurrent trastuzumab and adjuvant breast radiotherapy: a single institution series. Med Oncol 31:891

    Article  PubMed  Google Scholar 

  14. Caussa L, Kirova YM, Gault N et al (2011) The acute skin and heart toxicity of a concurrent association of trastuzumab and locoregional breast radiotherapy including internal mammary chain: a single-institution study. Eur J Cancer 47:65–73

    Article  CAS  PubMed  Google Scholar 

  15. Raben A, Sammons S, Hanlon A et al (2006) Comparison of acute breast and chest wall toxicity in women treated with external beam irradiation with and without concurrent herceptin in a community cancer center. Int J Radiat Oncol Biol Phys 66(Suppl):S541–S542

    Article  Google Scholar 

  16. Horton JK, Halle J, Ferraro M et al (2010) Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. Int J Radiat Oncol Biol Phys 76:998–1004

    Article  CAS  PubMed  Google Scholar 

  17. American Joint Committee on Cancer (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Book  Google Scholar 

  18. Pierga JY, Bidard FC, Mathiot C et al (2008) Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 14:7004–7010

    Article  CAS  PubMed  Google Scholar 

  19. Bollet MA, Sigal-Zafrani B, Gambotti L et al (2006) Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study. Eur J Cancer 42:2286–2295

    Article  CAS  PubMed  Google Scholar 

  20. Roché H, Fumoleau P, Spielmann M et al (2006) Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 24:5664–5671

    Article  PubMed  Google Scholar 

  21. Kirova YM, Hijal T, Campana F et al (2014) Whole breast radiotherapy in the lateral decubitus position: a dosimetric and clinical solution to decrease the doses to the organs at risk (OAR). Radiother Oncol 110:477–481

    Article  PubMed  Google Scholar 

  22. Fournier-Bidoz N, Kirova YM, Campana F et al (2012) Simplified field-in-field technique for a large-scale implementation in breast radiation treatment. Med Dosim 2012 Summer 37:131–137

    Google Scholar 

  23. Kirova YM, Campana F, Fournier-Bidoz N et al (2007) Postmastectomy electron beam chest wall irradiation in women with breast cancer: a clinical step toward conformal electron therapy. Int J Radiat Oncol Biol Phys 69:1139–1144

    Article  PubMed  Google Scholar 

  24. Hurkmans CW, Borger JH, Bos LJ et al (2000) Cardiac and lung complication probabilities after breast cancer irradiation. Radiother Oncol 55:145–151

    Article  CAS  PubMed  Google Scholar 

  25. Kong FM, Klein EE, Bradley JD et al (2002) The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart dose for intact breast radiation. Int J Radiat Oncol Biol Phys 54:963–971

    Article  PubMed  Google Scholar 

  26. Halyard MY, Pisansky TM, Dueck AC et al (2009) Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG phase III Trial N9831. J Clin Oncol 27:2638–2644

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Belkacémi Y, Gligorov J (2010) Concurrent trastuzumab-internal mammary irradiation for HER2 positive breast cancer: “It hurts to be on the cutting edge”. Radiother Oncol 94:119–120

    Article  PubMed  Google Scholar 

  28. Prosnitz RG, Marks LB (2005) Radiation-induced heart disease: vigilance is still required. J Clin Oncol 23:7391–7394

    Article  PubMed  Google Scholar 

  29. Whelan TJ, Olivotto I, Ackerman I et al (2011) NCIC-CTG MA.20: an intergroup trial of regional nodal irradiation in early breast cancer. J Clin Oncol 29 (Suppl):abstract LBA1003

  30. Poortmans P, Struikmans H, Kirkove C et al (2013) Irradiation of the internal mammary and medial supraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC Radiation Oncology and Breast Cancer Groups phase III trial 22922/10925. Eur J Cancer 49(Suppl 3):S1–S2

    Google Scholar 

  31. Hennequin C, Bossard N, Servagi-Vernat S et al (2013) Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys 86:860–866

    Article  PubMed  Google Scholar 

  32. Chang JS, Park W, Kim YB et al (2013) Long-term survival outcomes following internal mammary node irradiation in stage II–III breast cancer: results of a large retrospective study with 12 year follow-up. Int J Radiat Oncol Biol Phys 86:867–872

    Article  PubMed  Google Scholar 

  33. Harris EE, Correa C, Hwang WT et al (2006) Late cardiac mortality and morbidity in early stage breast cancer patients after breast-conservation treatment. J Clin Oncol 24:4100–4106

    Article  PubMed  Google Scholar 

  34. Tarantini L, Cioffi G, Gori S et al (2012) Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail 18:113–119

    Article  CAS  PubMed  Google Scholar 

  35. Tarantini L, Gori S, Faggiano P et al (2012) Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis. Ann Oncol 23:3058–3063

    Article  CAS  PubMed  Google Scholar 

  36. Taylor CW, McGale P, Povall JM et al (2009) Estimating cardiac exposure from breast cancer radiotherapy in clinical practice. Int J Radiat Oncol Biol Phys 73:1061–1068

    Article  CAS  PubMed  Google Scholar 

  37. Bornstein BA, Chang CW, Rhodes LM et al (1990) Can simulation measurements be used to predict the irradiated lung volume in the tangential fields in patients treated for breast cancer? Int J Radiat Oncol Biol Phys 18:181–187

    Article  CAS  PubMed  Google Scholar 

  38. Neal AJ, Yarnold JR (1995) Estimating the volume of lung irradiated during tangential breast irradiation using the central lung distance. Br J Radiol 68:1004–1008

    Article  CAS  PubMed  Google Scholar 

  39. Das IJ, Cheng EC, Freedman G et al (1998) Lung and heart dose volume analyses with CT simulator in radiation treatment of breast cancer. Int J Radiat Oncol Biol Phys 42:11–19

    Article  CAS  PubMed  Google Scholar 

  40. Coon AB, Dickler A, Kirk MC et al (2010) Tomotherapy and multifield intensity-modulated radiotherapy planning reduce cardiac doses in left-sided breast cancer patients with unfavorable cardiac anatomy. Int J Radiat Oncol Biol Phys 78:104–110

    Article  PubMed  Google Scholar 

  41. Quinn A, Holloway L, Hardcastle N et al (2013) Normal tissue dose and second cancer risk due to megavoltage fan-beam CT, static tomotherapy and helical tomotherapy in breast radiotherapy. Radiother Oncol 108:266–268

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the patients followed throughout this study and the members of the Institut Curie Breast Cancer Study Group. We would also like to thank Dr Marc Bollet, Dr Caroline Daveau-Bergerault, Dr Lucas Caussa, and Mrs. Chantal Gautier for their help in the patient data management.

Conflict of interest

J.-Y. P.: fees, research grants received from Roche® laboratories. P. B.: fees received from Roche® laboratories. All remaining authors have declared no conflicts of interest.

Fundings

The authors have declared no funding sources for this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Jacob.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jacob, J., Belin, L., Pierga, JY. et al. Concurrent administration of trastuzumab with locoregional breast radiotherapy: long-term results of a prospective study. Breast Cancer Res Treat 148, 345–353 (2014). https://doi.org/10.1007/s10549-014-3166-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-3166-5

Keywords

Navigation