Skip to main content

Advertisement

SpringerLink
Log in

Cutaneous and cardiac toxicity of concurrent trastuzumab and adjuvant breast radiotherapy: a single institution series

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Pilot studies have shown that patients with human epidermal growth factor receptor 2-positive disease have greater risk of relapse and death. The sooner trastuzumab is administered, the greater seems to be the benefit. A delay in the initiation of adjuvant radiotherapy (RT) may result in an increased rate of local recurrence. Since limited published data exist, the aim of our analyses was to evaluate the skin and heart toxicity of concomitant treatment. Between 2003 and 2012, 95 women were treated at our Institute by concomitant therapy for clinical stage I–III invasive breast cancer. Cardiac toxicity was evaluated according to the left ventricular ejection fraction (LVEF) decrease, with a prospective monitoring program. All acute and late toxicities were assessed according to the CTCAE-v3 criteria. At a median follow-up of 4.3 years (range 1.3–10.4), 5 patients developed locoregional relapse and 7 patients developed distant metastases; disease-free survival was 90 % and overall survival 97.9 %. Overall, skin toxicity ≥Grade 2 was recorded in 13 patients (13.7 %). No dysphagia and esophagitis ≥Grade 2 were recorded. Cosmetic outcome was excellent in 41 patients (43.2 %), good in 39 patients (41.1 %), and fair in 10 patients (10.5 %). All patients concluded the programmed RT. Among the 58 patients (61.1 %) that recorded a LVEF dysfunction, the median decrease from baseline to the end of trastuzumab was 10 %, while the median decrease from baseline to the last follow-up was 7 % (p = 0.01). In our experience, concomitant trastuzumab and radiation treatment was overall well tolerated.

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

Similar content being viewed by others

References

  1. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.

    Article  CAS  PubMed  Google Scholar 

  2. Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Oncologist. 1998;3:237–52.

    PubMed  Google Scholar 

  3. Menard S, Balsari A, Casalini P, et al. HER-2-positive breast carcinomas as a particular subset with peculiar clinical behaviors. Clin Cancer Res. 2002;8:520–5.

    CAS  PubMed  Google Scholar 

  4. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  CAS  PubMed  Google Scholar 

  5. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.

    Article  CAS  PubMed  Google Scholar 

  6. Caussa L, Kirova YM, Gault N, et al. 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. 2011;47:65–73.

    Article  CAS  PubMed  Google Scholar 

  7. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809–20.

    Article  CAS  PubMed  Google Scholar 

  8. Huang J, Barbera L, Brouwers M, et al. Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol. 2003;21:555–63.

    Article  PubMed  Google Scholar 

  9. Livi L, Borghesi S, Saieva C, et al. Radiotherapy timing in 4,820 patients with breast cancer: university of Florence experience. Int J Radiat Oncol Biol Phys. 2009;73:365–9.

    Article  PubMed  Google Scholar 

  10. Liang K, Lu Y, Jin W, et al. Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther. 2003;2:1113–20.

    CAS  PubMed  Google Scholar 

  11. Perez EA. Cardiac toxicity of ErbB2-targeted therapies: what do we know? Clin Breast Cancer. 2008;3:S114–20.

    Article  Google Scholar 

  12. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23:7811–9.

    Article  CAS  PubMed  Google Scholar 

  13. Belkacémi Y, Gligorov J, Ozsahin M, et al. Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. Ann Oncol. 2008;19:1110–6.

    Article  PubMed  Google Scholar 

  14. Halyard MY, Pisansky TM, Dueck AC, et al. Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG phase III trial N9831. J Clin Oncol. 2009;27:2638–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Perez EA, Suman VJ, Davidson NE, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26:1231–8.

    Article  CAS  PubMed  Google Scholar 

  16. 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;366:2087–106.

    Article  CAS  PubMed  Google Scholar 

  17. Fiets WE, van Helvoirt RP, Nortier JW, et al. Acute toxicity of concurrent adjuvant radiotherapy and chemotherapy (CMF or AC) in breast cancer patients: a prospective, comparative, non-randomised study. Eur J Cancer. 2003;39:1081–8.

    Article  CAS  PubMed  Google Scholar 

  18. Ismaili N, Mellas N, Masbah O, et al. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer. Radiat Oncol. 2009;4:12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Valagussa P, Zambetti M, Biasi S, et al. Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer. Ann Oncol. 1994;5:209–16.

    Article  CAS  PubMed  Google Scholar 

  20. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med. 2001;344:1997–2008.

    Article  CAS  PubMed  Google Scholar 

  21. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.

    Article  PubMed  Google Scholar 

  22. Trombetta M, Julian TB, Kim Y, Werst ED, Parda D. The allegheny general modification of the Harvard Breast Cosmesis Scale for the retreated breast. Oncology. 2009;23:954–6.

    PubMed  Google Scholar 

  23. Livi L, Borghesi S, Meattini I, et al. Adjuvant trastuzumab in breast cancer: experience from the University of Florence. J Chemother. 2010;22:115–8.

    Article  CAS  PubMed  Google Scholar 

  24. Livi L, Meattini I, de Luca Cardillo C, et al. Use of doxorubicin plus cyclophosphamide followed by docetaxel as adjuvant chemotherapy for breast cancer. J Chemother. 2011;23:36–9.

    Article  CAS  PubMed  Google Scholar 

  25. Livi L, Meattini I, Franceschini D, et al. Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy. Radiother Oncol. 2013;108:273–8.

    Article  PubMed  Google Scholar 

  26. ICRU. Report 50: prescribing, recording, and reporting photon beam therapy. Washington: International Commission on Radiation Units and Measurements; 1993.

    Google Scholar 

  27. Meattini I, Livi L, Saieva C, et al. Prognostic role of human epidermal growth factor receptor 2 status in premenopausal early breast cancer treated with adjuvant tamoxifen. Clin Breast Cancer. 2013;13:247–53.

    Article  CAS  PubMed  Google Scholar 

  28. Meattini I, Livi L, Franceschini D, et al. Role of radiotherapy boost in women with ductal carcinoma in situ: a single-center experience in a series of 389 patients. Eur J Surg Oncol. 2013;39:613–8.

    Article  CAS  PubMed  Google Scholar 

  29. Livi L, Meattini I, Saieva C, et al. Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer. Cancer. 2012;118:3236–43.

    Article  CAS  PubMed  Google Scholar 

  30. Kun Y, How LC, Hoon TP, et al. Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor. Hum Mol Genet. 2003;12:3245–58.

    Article  CAS  PubMed  Google Scholar 

  31. DeCensi A, Guerrieri-Gonzaga A, Gandini S, et al. Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer. Ann Oncol. 2011;22:582–7.

    Article  CAS  PubMed  Google Scholar 

  32. Munzone E, Botteri E, Sciandivasci A, et al. Prognostic value of Ki-67 labeling index in patients with node-negative, triple-negative breast cancer. Breast Cancer Res Treat. 2012;134:277–82.

    Article  PubMed  Google Scholar 

  33. Dowsett M, Nielsen TO, A’Hern R, et al. Assessment of Ki67 in breast cancer: recommendations from the international Ki67 in breast cancer working group. J Natl Cancer Inst. 2011;103:1656–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Sobin L, Gospodarowicz M, Wittekind C, editors. TNM Classification of malignant tumors. 7th ed. Hoboken: Wiley; 2009.

    Google Scholar 

  35. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer: I. The value of histological grade in breast cancer—experience from a large study with long-term follow-up. Histopathology. 2002;41:151–2.

    Article  CAS  PubMed  Google Scholar 

  36. Jacob J, Berlin L, Pierga J-Y, et al. Concurrent loco-regional radiotherapy and trastuzumab in early-stage breast cancer: long term results of prospective single-institution study. Cancer Res. 2012;72(suppl 3):485s.

    Google Scholar 

  37. Gujral DM, Lloyd G, Bhattacharyya S. Cardiac toxicity monitoring for HER2-positive breast cancer patients undergoing trastuzumab therapy: are we doing enough? Clin Oncol (R Coll Radiol). 2013;25:446–7.

    Article  CAS  Google Scholar 

  38. Ewer MS, Tan-Chiu E. Reversibility of trastuzumab cardiotoxicity: is the concept alive and well? J Clin Oncol. 2007;25:5532–3.

    Article  PubMed  Google Scholar 

  39. Telli ML, Hunt SA, Carlson RW, et al. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007;25:3525–33.

    Article  CAS  PubMed  Google Scholar 

  40. Jones AL, Barlow M, Barrett-Lee PJ, et al. Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring. Br J Cancer. 2009;100:684–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Johri AM, Picard MH, Newell J, et al. Can a teaching intervention reduce interobserver variability in LVEF assessment: a quality control exercise in the echocardiography lab. JACC Cardiovasc Imaging. 2011;4:821–9.

    Article  PubMed  Google Scholar 

  42. Lang RM, Bierig M, Devereux RB, et al. Recommendation for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group. J Am Soc Echocardiogr. 2005;18:1440–63.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Dang C, Fornier M, Sugarman S, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008;26:1216–22.

    Article  CAS  PubMed  Google Scholar 

  45. Matzinger O, Heimsoth I, Poortmans P, et al. Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925). Acta Oncol. 2010;49:24–34.

    Article  PubMed  Google Scholar 

  46. Poortmans P, Struikmans H, Kirkove C, et al. 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. 2013;49(Suppl 3):S1–19.

    Google Scholar 

  47. Dellapasqua S, Bagnardi V, Balduzzi A, et al. Outcomes of patients with breast cancer who present with ipsilateral supraclavicular or internal mammary lymph node metastases. Clin Breast Cancer. 2014;14:53–60.

    Article  PubMed  Google Scholar 

  48. Shaffer R, Tyldesley S, Rolles M, et al. Acute cardiotoxicity with concurrent trastuzumab and radiotherapy including internal mammary chain nodes: a retrospective single-institution study. Radiother Oncol. 2009;90:122–6.

    Article  CAS  PubMed  Google Scholar 

  49. Castro Pena P, Kirova YM, Campana F, et al. Anatomical, clinical and radiological delineation of target volumes in breast cancer radiotherapy planning: individual variability, questions and answers. Br J Radiol. 2009;82:595–9.

    Article  CAS  PubMed  Google Scholar 

  50. Kirova YM, Castro Pena P, Dendale R, et al. Simplified rules for everyday delineation of lymph node areas for breast cancer radiotherapy. Br J Radiol. 2010;83:683–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Radiation-Oncology, University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy

    Icro Meattini, Sara Cecchini, Cristina Muntoni, Vieri Scotti, Carla De Luca Cardillo, Monica Mangoni, Pierluigi Bonomo & Lorenzo Livi

  2. Diagnostic Senology Unit, University of Florence, Florence, Italy

    Jacopo Nori

  3. Department of Surgery, University of Florence, Florence, Italy

    Donato Casella, Roberta Simoncini & Lorenzo Orzalesi

  4. Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    Simonetta Bianchi

Authors
  1. Icro Meattini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Cecchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Muntoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vieri Scotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carla De Luca Cardillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monica Mangoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pierluigi Bonomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jacopo Nori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Donato Casella
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Roberta Simoncini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lorenzo Orzalesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Simonetta Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lorenzo Livi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Icro Meattini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meattini, I., Cecchini, S., Muntoni, C. et al. Cutaneous and cardiac toxicity of concurrent trastuzumab and adjuvant breast radiotherapy: a single institution series. Med Oncol 31, 891 (2014). https://doi.org/10.1007/s12032-014-0891-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0891-x

Keywords

Search

Navigation