International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 4 , Pages 998-1004 , 15 March 2010

Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

Presented at the 48th American Society for Therapeutic Radiology and Oncology Annual Meeting, November 5–9, 2006, Philadelphia, PA.

  • Janet K. Horton, M.D.

      Affiliations

    • Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
    • Corresponding Author InformationReprint requests to: Janet K. Horton, M.D., Department of Radiation Oncology, Duke University Medical Center, DUMC 3085, Durham, NC 27710. Tel: (919) 668-5213; Fax: (919) 668-7345
  • ,
  • Jan Halle, M.D.

      Affiliations

    • Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
  • ,
  • Madlyn Ferraro, R.N.

      Affiliations

    • Lineberger Comprehensive Cancer Center, Chapel Hill, NC
  • ,
  • Lisa Carey, M.D.

      Affiliations

    • Department of Internal Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
  • ,
  • Dominic T. Moore, M.P.H.

      Affiliations

    • Lineberger Comprehensive Cancer Center, Chapel Hill, NC
  • ,
  • David Ollila, M.D.

      Affiliations

    • Department of Surgery, Division of Surgical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
  • ,
  • Carolyn I. Sartor, M.D.

      Affiliations

    • Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC

Received 26 November 2008 ,Revised 5 March 2009 ,Accepted 12 March 2009.

References 

  1. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–182
  2. Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5:63–69
  3. Sjögren S, Inganas M, Lindgren A, et al. Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol. 1998;16:462–469
  4. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–712
  5. Yakes FM, Chinratanalab W, Ritter CA, et al. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res. 2002;62:4132–4141
  6. Gennari R, Menard S, Fagnoni F, et al. Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res. 2004;10:5650–5655
  7. Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment of HER2-positive breast cancer: An antibody-dependent cellular cytotoxicity mechanism?. Br J Cancer. 2006;94:259–267
  8. 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;344:783–792
  9. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639–2648
  10. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719–726
  11. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–1684
  12. Smith I, Procter M, Gelber RD, et al. 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomized controlled trial. Lancet. 2007;369:29–36
  13. Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER-2/neu receptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of breast cancer cells overexpressing this oncogene. Cancer Res. 1999;59:1347–1355
  14. Liang K, Lu Y, Jin W, et al. Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther. 2003;2:1113–1120
  15. Haffty BG, Brown F, Carter D, et al. Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study. Int J Radiat Oncol Biol Phys. 1996;35:751–757
  16. Huang EH, Tucker SL, Strom EA, et al. Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:351–357
  17. Rastogi P, Jeong J, Geyer CE, et al. Five year update of cardiac dysfunction on NSABP B-31: A randomized trial of AC→paclitaxel vs. AC→paclitaxel with trastuzumab in HER2 positive, node positive operable breast cancer [Abstract]. Proc Am Soc Clin Oncol. 2007;25:6s
  18. 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;23:7211–7819
  19. 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;26:1231–1238
  20. Slamon DJ, Eiermann W, Robert N, et al. Phase III trial comparing AC-T with AC-TH and with TCH in the adjuvant treatment of HER2-positive early breast cancer patients: Second interim efficacy analysis [Abstract]. Breast Cancer Res Treat. 2006;100:S63(52a)
  21. Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23:7820–7826
  22. Harris EE, Correa C, Hwang WT, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24:4100–4106
  23. Cusick J, Stewart H, Rutqvist L, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol. 1994;12:447–453
  24. Fleming ID, Cooper JS, Henson DE, et al. AJCC cancer staging manual. 5th ed.. Philadelphia: Lippincott-Raven; 1997;p. 294
  25. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual. 6th ed.. New York: Springer; 2002;p. 421
  26. Kelly H, Kimmick G, Dees EC, et al. Response and cardiac toxicity of trastuzumab given in conjunction with weekly paclitaxel after doxorubicin/cyclophosphamide. Clin Breast Cancer. 2006;7:237–243
  27. Vincent-Salomon A, Jouve M, Genin P, et al. HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process. Cancer. 2002;94:2169–2173
  28. Huang E, McNeese MD, Strom EA, et al. Locoregional treatment outcomes for inoperable anthracycline-resistant breast cancer. Int J Radiat Oncol Biol Phys. 2002;53:1225–1233
  29. Chakravarthy AB, Kelley MC, McLaren B, et al. Neoadjuvant concurrent paclitaxel and radiation in stage II/III breast cancer. Clin Cancer Res. 2006;12:1570–1576
  30. Perkins GH, Middleton LP, Tran R, et al. Concurrent chemoradiation with capecitabine achieves meritable response and local control for inoperable and recurrent neoadjuvant chemotherapy refractory breast cancer [Abstract]. Breast Cancer Res Treat. 2007;106:S191
  31. Burstein HJ, Bellon JR, Galper S, et al. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for stage II or III breast cancer. Int J Radiat Oncol Biol Phys. 2006;64:496–504
  32. 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;19:1110–1116
  33. Liao Z, Strom EA, Buzdar AU, et al. Locoregional irradiation for inflammatory breast cancer: Effectiveness of dose escalation in decreasing recurrence. Int J Radiat Oncol Biol Phys. 2000;47:1191–1200
  34. Fastenberg NA, Martin RG, Buzdar AU, et al. Management of inflammatory carcinoma of the breast. A combined modality approach. Am J Clin Oncol. 1985;8:134–141
  35. Ueno NT, Buzdar AU, Singletary SE, et al. Combined-modality treatment of inflammatory breast carcinoma: Twenty years of experience at M.D. Anderson Cancer Center. Cancer Chemother Pharmacol. 1997;40:321–329
  36. 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;366:2087–2106

 Support and third-party writing assistance provided by Genentech USA, Inc., South San Francisco, CA.

 Conflict of interest: none.

PII: S0360-3016(09)00464-7

doi: 10.1016/j.ijrobp.2009.03.027

International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 4 , Pages 998-1004 , 15 March 2010