Sequencing of Systemic Treatment and Radiotherapy

  • Pia Ursula Huguenin†
Part of the Cancer Treatment and Research book series (CTAR, volume 151)

The mortality of breast cancer is mainly due to metastatic disease, and the majority of clinical trials are aimed at the optimization of systemic treatments in order to reduce the risk for the development of a systemic disease. In early years, following the observation of outcome in large numbers of patients with specific disease profiles supposed to be risk factors, surgery was supplemented by ortho-voltage radiotherapy and ovarian ablation as the first form of systemic treatment. The efficacy of radiotherapy was analyzed in very early randomized trials. The question of sequencing was addressed only later, with the availability of many active drugs and the establishment of breast-conserving therapy including radiotherapy to the remaining breast.


Inflammatory Breast Cancer Late Toxicity Sequential Application Combine Modality Treatment Ovarian Ablation 


  1. 1.
    Kurtz J. The curative role of radiotherapy in the treatment of operable breast cancer. Eur J Cancer. 2002;38:1961–74.PubMedCrossRefGoogle Scholar
  2. 2.
    Group EBCTsC: Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Early breast cancer trialists' collaborative group. Lancet. 2000;355:1757–70.CrossRefGoogle Scholar
  3. 3.
    Poortmans P. Evidence based radiation oncology: Breast cancer. Radiother Oncol. 2007;84:84–101.PubMedCrossRefGoogle Scholar
  4. 4.
    Beil DR, Wein LM: Sequencing surgery, radiotherapy and chemotherapy: Insights from a mathematical analysis. Breast Cancer Res Treat. 2002;74:279–86.PubMedCrossRefGoogle Scholar
  5. 5.
    Wallgren A, Bernier J, Gelber RD, Goldhirsch A, Roncadin M, Joseph D, Castiglione-Gertsch M: Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. International breast cancer study group. Int J Radiat Oncol Biol Phys. 1996;35:649–59.PubMedCrossRefGoogle Scholar
  6. 6.
    Huang J, Barbera L, Brouwers M, Browman G, Mackillop WJ. Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol. 2003;21:555–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Hershman DL, Wang X, McBride R, Jacobson JS, Grann VR, Neugut AI. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival. Int J Radiat Oncol Biol Phys. 2006;65:1353–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Thomas GM. Improved treatment for cervical cancer – concurrent chemotherapy and radiotherapy. N Engl J Med. 1999;340:1198–200.PubMedCrossRefGoogle Scholar
  9. 9.
    Auperin A, Le Pechoux C, Pignon JP, Koning C, Jeremic B, Clamon G, Einhorn L, Ball D, Trovo MG, Groen HJ, Bonner JA, Le Chevalier T, Arriagada R. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (nsclc): A meta-analysis of individual data from 1764 patients. Ann Oncol. 2006;17:473–83.PubMedCrossRefGoogle Scholar
  10. 10.
    Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. Mach-nc collaborative group. Meta-analysis of chemotherapy on head and neck cancer. Lancet. 2000;355:949–55.PubMedGoogle Scholar
  11. 11.
    Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.PubMedCrossRefGoogle Scholar
  12. 12.
    Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. 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;337:949–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ, Olivotto IA. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337:956–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD. Adding adjuvant cmf chemotherapy to either radiotherapy or tamoxifen: Are all cmfs alike? The international breast cancer study group (ibcsg). Ann Oncol. 1998;9:489–93.PubMedCrossRefGoogle Scholar
  15. 15.
    Dubey A, Recht A, Come SE, Gelman RS, Silver B, Harris JR, Shulman LN. Concurrent cmf and radiation therapy for early stage breast cancer: Results of a pilot study. Int J Radiat Oncol Biol Phys. 1999;45:877–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Liao Z, Strom EA, Buzdar AU, Singletary SE, Hunt K, Allen PK, McNeese MD. Locoregional irradiation for inflammatory breast cancer: Effectiveness of dose escalation in decreasing recurrence. Int J Radiat Oncol Biol. Phys 2000;47:1191–2000.CrossRefGoogle Scholar
  17. 17.
    Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C, Dendale R, Campana F, Kirova YM, Dieras V, Fourquet A. Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: Results of a phase ii study. Eur J Cancer. 2006;42:2286–95.PubMedCrossRefGoogle Scholar
  18. 18.
    Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996;334:1356–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Bellon JR, Come SE, Gelman RS, Henderson IC, Shulman LN, Silver BJ, Harris JR, Recht A. Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: Updated results of a prospective randomized trial. J Clin Oncol. 2005;23:1934–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Arcangeli G, Pinnaro P, Rambone R, Giannarelli D, Benassi M. A phase iii randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer. Int J Radiat Oncol Biol. Phys. 2006;64:161–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Toledano A, Garaud P, Serin D, Fourquet A, Bosset JF, Breteau N, Body G, Azria D, Le Floch O, Calais G. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the arcosein multicenter randomized study. Int J Radiat Oncol Biol Phys. 2006;65:324–32.PubMedCrossRefGoogle Scholar
  22. 22.
    Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J. Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst. 1996;88:918–22.PubMedCrossRefGoogle Scholar
  23. 23.
    Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Nesbitt L, Paik S, Pisansky TM, Wolmark N. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002;20:4141–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Harris EE, Christensen VJ, Hwang WT, Fox K, Solin LJ. Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment. J Clin Oncol. 2005;23:11–16.PubMedCrossRefGoogle Scholar
  25. 25.
    Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, Osborne CK, Albain KS. Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer. J Clin Oncol. 2005;23:24–29.PubMedCrossRefGoogle Scholar
  26. 26.
    Horsman MR, Bohm L, Margison GP, Milas L, Rosier JF, Safrany G, Selzer E, Verheij M, Hendry JH. Tumor radiosensitizers – current status of development of various approaches: Report of an international atomic energy agency meeting. Int J Radiat Oncol Biol Phys. 2006;64:551–61.Google Scholar
  27. 27.
    Tannock IF. Treatment of cancer with radiation and drugs. J Clin Oncol. 1996;14:3156–74.PubMedGoogle Scholar
  28. 28.
    Wardman P. Chemical radiosensitizers for use in radiotherapy. Clin Oncol. (R Coll Radiol). 2007;19:397–417.CrossRefGoogle Scholar
  29. 29.
    Halyard MY, Pisansky TM, Solin LJ, Marks LB, Pierce LJ, Dueck A, Perez EA. Adjuvant radiotherapy (rt) and trastuzumab in stage i–iia breast cancer: Toxicity data from north central cancer treatment group phase iii trial n9831. J Clin Oncol (Meeting Abstracts). 2006;24:523.Google Scholar
  30. 30.
    Dewar JA, Haviland JS, Agrawal RK, Bliss JM, Hopwood P, Magee B, Owen JR, Sydenham MA, Venables K, Yarnold JR, on behalf of the STc. Hypofractionation for early breast cancer: First results of the UK standardization of breast radiotherapy (start) trials. J Clin Oncol (Meeting Abstracts). 2007;25:LBA518.Google Scholar
  31. 31.
    Holmes DR, Baum M, Joseph D. The targit trial: Targeted intraoperative radiation therapy versus conventional postoperative whole-breast radiotherapy after breast-conserving surgery for the management of early-stage invasive breast cancer (a trial update). Am J Surg. 2007;194:507–10.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Pia Ursula Huguenin†
    • 1
  1. 1.Radiation Therapy DepartmentKantonsspital GraubündenChurSwitzerland

Personalised recommendations