Clinical Oncology
Volume 18, Issue 3 , Pages 247-256 , April 2006

Delaying Radiotherapy for the Delivery of Adjuvant Chemotherapy in the Combined Modality Treatment of Early Breast Cancer: Is It Disadvantageous and Could Combined Treatment be the Answer?

  • S.J. Bowden

      Affiliations

    • CR UK Clinical Trials Unit, Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK
    • Corresponding Author InformationAuthor for correspondence: Dr S. J. Bowden, CR UK Clinical Trials Unit, Institute for Cancer Research, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Tel: +44-121-414-4371; Fax: +44-121-414-3700.
    • ,
  • I.N. Fernando

      Affiliations

    • Queen Elizabeth Hospital, Edgbaston, Birmingham, UK
    • ,
  • A. Burton

      Affiliations

    • CR UK Clinical Trials Unit, Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK

References 

  1. Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998;352:930–942
  2. Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355:1757–1770
  3. Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol. 2000;18:1220–1229
  4. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med. 1997;337:949–955
  5. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337:956–962
  6. van der Hage JA, Putter H, Bonnema J, Bartelink H, Therasse P, van de Velde CJH. Impact of locoregional treatment on the early-stage breast cancer patients: a retrospective analysis. Eur J Cancer. 2003;39:2192–2199
  7. Vinh-Hung V, Burzykowski T, Van de Steene J, Storme G, Soete G. Post-surgery radiation in early breast cancer: survival analysis of registry data. Radiother Oncol. 2002;64:281–290
  8. Højris I, Overgaard M, Christensen JJ, Overgaard J. Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Lancet. 1999;354:1425–1430
  9. McBain CA, Young EA, Swindell R, Magee B, Stewart AL. Local recurrence of breast cancer following surgery and radiotherapy: incidence and outcome. Clin Oncol. 2003;15:25–31
  10. Monteiro Grillo I, Jorge M, Marques Vidal P, Ortiz M, Ravasco P. The effect of locoregional recurrence on survival and distant metastasis after conservative treatment for invasive breast carcinoma. Clin Oncol. 2005;17:111–117
  11. Poole CJ, Earl HM, Dunn JA, et al. NEAT (National Epirubicin Adjuvant Trial) and SCTBG BR9601 (Scottish Cancer Trials Breast Group) phase III adjuvant breast trials show a significant relapse-free and overall survival advantage for sequential ECMF. [abstract 13] Proc Am Soc Clin Oncol. 2003;22
  12. Clarke DH, Lê MG, Sarrazin D, et al. Analysis of loco-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys. 1985;11:137–145
  13. Nixon AJ, Recht A, Neuberg DA, et al. The relation between the surgery–radiotherapy interval and treatment outcome in patients treated with breast-conserving surgery and radiation therapy without systemic therapy. Int J Radiat Oncol Biol Phys. 1994;30:17–21
  14. Vujovic O, Perera F, Dar AR, et al. Does delay in breast irradiation following conservative breast surgery in node-negative breast cancer patients have an impact on risk of recurrence?. Int J Radiat Oncol Biol Phys. 1998;40:869–874
  15. Froud PJ, Mates D, Jackson JSH, et al. Effect of time interval between breast-conserving surgery and radiation therapy on ipsilateral breast recurrence. Int J Radiat Oncol Biol Phys. 2000;46:363–372
  16. Slotman BJ, Meyer OWM, Njo KH, Karim ABMF. Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer. Radiother Oncol. 1994;30:206–212
  17. Leonard CE, Wood ME, Zhen B, et al. Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?. J Clin Oncol. 1995;13:2906–2915
  18. McCormick B, Norton L, Yao TJ, Yahalom J, Petrek JA. The impact of the sequence of radiation and chemotherapy on local control after breast-conserving surgery. Cancer J Sci Am. 1996;2:39–45
  19. Meek AG, Park TL, Weiss TA, Bethune WA. Effect of delayed radiation therapy on local control in breast conservation therapy. Radiology. 1996;200:615–619
  20. Ampil FL, Burton GV, Li BDL, Mills GM. Radiotherapy with and without chemotherapy after breast conservation surgery for early stage breast cancer: a review of timing. Eur J Gynaecol Oncol. 1999;20:254–259
  21. Metz JM, Schultz DJ, Fox K, Mathews A, Glick J, Solin LJ. Analysis of outcomes for high-risk breast cancer based on interval from surgery to postmastectomy radiation therapy. Cancer J. 2000;6:324–330
  22. Donato V, Monaco A, Messina F, et al. Local recurrence in breast cancer after conservative surgery: timing of radiotherapy and sequencing of chemotherapy. Anticancer Res. 2004;24:1303–1306
  23. Yock TI, Taghian AG, Kachnic LA, Coen JJ, Assaad SI, Powell SN. The effect of delaying radiation therapy for systemic chemotherapy on local–regional control in breast cancer. Breast Cancer Res Treat. 2004;84:161–171
  24. Wallgren A, Bernier J, Gelber RD, et al. Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. Int J Radiat Oncol Biol Phys. 1996;35:649–659
  25. Pierce LJ, Lew D, Hutchins L, et al. Patterns of recurrence by sequence of chemotherapy and radiotherapy in early stage breast cancer. [abstract 6] Int J Radiat Oncol Biol Phys. 2003;57(suppl 1):127
  26. Sartor CI, Peterson BL, Woolf S, et al. Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: cancer and leukemia group B 9344. J Clin Oncol. 2005;23:30–40
  27. Kurtz JM. Can more breasts be saved if chemotherapy and radiotherapy are administered concomitantly?. Ann Oncol. 1999;10:1409–1411
  28. Recht A, Come SE, Gelman RS, et al. Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome. J Clin Oncol. 1991;9:1662–1667
  29. Buchholz TA, Austin-Seymour MM, Moe RE, et al. Effect of delay in radiation in the combined modality treatment of breast cancer. Int J Radiat Oncol Biol Phys. 1993;26:23–35
  30. Buzdar AU, Kan SW, Smith TL, et al. The order of administration of chemotherapy and radiation and its effect on the local control of operable breast cancer. Cancer. 1993;71:3680–3684
  31. Nguyen TD, Naja A, Chaplain G, Mere P. Role of delay between surgery and radiotherapy on the outcome of patients with node positive breast cancer. Bull Cancer Radiother. 1993;80:229–233
  32. Hartsell WF, Recine DC, Griem KL, Murthy AK. Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence. Cancer. 1995;76:2497–2503
  33. Buchholz TA, Hunt KK, Amosson CM, et al. Sequencing of chemotherapy and radiation in lymph node-negative breast cancer. Cancer J Sci Am. 1999;5:159–164
  34. Benk V, Joseph L, Fortin P, et al. Effect of delay in initiating radiotherapy for patients with early stage breast cancer. Clin Oncol. 2004;16:6–11
  35. Hébert-Croteau N, Freeman CR, Latreille J, Rivard M, Brisson J. A population-based study of the impact of delaying radiotherapy after conservative surgery for breast cancer. Breast Cancer Res Treat. 2004;88:187–196
  36. Mikeljevic JS, Haward R, Johnston C, et al. Trends in postoperative radiotherapy delay and the effect on survival in breast cancer patients treated with conservation surgery. Br J Cancer. 2004;90:1343–1348
  37. 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;21:555–563
  38. Hébert-Croteau N, Freeman C, Latreille J, Brisson J. Delay of radiation therapy and outcomes of breast cancer. J Clin Oncol. 2004;22:1342–1343
  39. Recht A. Impact on outcome of delay in starting radiotherapy. J Clin Oncol. 2004;22:1341–1342
  40. Hahn P, Hallberg O, Vikterlof KJ. Acute skin reactions in postoperative breast cancer patients receiving radiotherapy plus adjuvant chemotherapy. Am J Roentgenol. 1978;130:137–139
  41. Denham JW, Hamilton CS, Christie D, et al. Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer: toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study. Int J Radiat Oncol Biol Phys. 1995;31:305–313
  42. Isaac N, Panzarella T, Lau A, et al. Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen. Cancer. 2002;95:696–703
  43. Faul C, Brufsky A, Gerszten K, et al. Concurrent sequencing of full-dose CMF chemotherapy and radiation therapy in early breast cancer has no effect on treatment delivery. Eur J Cancer. 2003;39:763–768
  44. Dubey A, Recht A, Come SE, et al. Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study. Int J Radiat Oncol Biol Phys. 1999;45:877–884
  45. Fernando IN, Powles TJ, Ashley S, Grafton D, Harmer CL, Ford HT. An acute toxicity study on the effects of synchronous chemotherapy and radiotherapy in early stage breast cancer after conservative surgery. Clin Oncol. 1996;8:234–238
  46. Fiets WE, van Helvoirt RP, Nortier JWR, van der Tweel I, Struikmans H. 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;39:1081–1088
  47. Pezner RD, Lipsett JA, Forell B, et al. The reverse hockey stick technique: postmastectomy radiation therapy for breast cancer patients with locally advanced tumor presentation or extensive loco-regional recurrence. Int J Radiat Oncol Biol Phys. 1989;17:191–197
  48. Mayer EG, Poulter CA, Aristizabal SA. Complications of irradiation related to apparent drug potentiation by adriamycin. Int J Radiat Oncol Biol Phys. 1976;1:1179–1188
  49. Hansen R, Erickson B, Komaki R, et al. Concomitant adjuvant chemotherapy and radiotherapy for high risk breast cancer patients. Breast Cancer Res Treat. 1990;17:171–177
  50. Bellon JR, Lindsley KL, Ellis GK, Gralow JR, Livingston RB, Austin Seymour MM. Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer. Int J Radiat Oncol Biol Phys. 2000;48:393–397
  51. Hanna YM, Baglan KL, Stromberg JS, Vicini FA, Decker DA. Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J. 2002;8:149–153
  52. Kao J, Conzen SD, Jaskowiak NT, et al. Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive Phase I/II trials. Int J Radiat Oncol Biol Phys. 2005;61:1045–1053
  53. Poole CJ, Howard HC, Hiller L, et al. A prospective evaluation of pulmonary, cardiac, and hepatic function (fn) in ‘tAnGo’: a randomized phase III trial of gemcitabine (G) in paclitaxel (T)-containing, epirubicin/cyclophosphamide (EC)-based, adjuvant chemotherapy (CT) for early stage breast cancer. [abstract 821] J Clin Oncol. 2004;22:14S
  54. Beadle GF, Come S, Henderson IC, Silver B, Hellman S, Harris JR. The effect of adjuvant chemotherapy on the cosmetic results after primary radiation treatment for early stage breast cancer. Int J Radiat Oncol Biol Phys. 1984;10:2131–2137
  55. Ray GR, Fish VJ, Marmor JB, et al. Impact of adjuvant chemotherapy on cosmesis and complications in stages I and II carcinoma of the breast treated by biopsy and radiation therapy. Int J Radiat Oncol Biol Phys. 1984;10:837–841
  56. Abner AL, Recht A, Vicini FA, et al. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys. 1991;21:331–338
  57. Taylor ME, Perez CA, Halverson KJ, et al. Factors influencing cosmetic results after conservation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 1995;31:753–764
  58. Markiewicz DA, Schultz DJ, Haas JA, et al. The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy. Int J Radiat Oncol Biol Phys. 1996;35:661–668
  59. Moro G, Stasi M, Borca VC. Does concomitant chemoradiotherapy influence cosmetic outcome in conservative treatment of breast cancer?. Tumori. 1997;83:743–747
  60. Bellon JR, Shulman LN, Come SE, et al. A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma. Cancer. 2004;100:1358–1364
  61. Blomqvist C, Tiusanen K, Elomaa I, et al. The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow-up results of a randomised trial. Br J Cancer. 1992;66:1171–1176
  62. Lingos TI, Recht A, Vicini F, Abner A, Silver B, Harris JR. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys. 1991;21:355–360
  63. Taghian AG, Assaad SI, Niemierko A, et al. Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst. 2001;93:1806–1811
  64. Hoogenraad WJ, Franssen JH, van Turnhout JM. Enhanced toxicity of radiotherapy due to epirubicin containing adjuvant chemotherapy in breast carcinoma patients. [abstract 158] Radiother Oncol. 1992;24(suppl):S42
  65. Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991;9:2134–2140
  66. Recht A, Come SE, Henderson IC, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996;334:1356–1361
  67. Bellon JR, Come SE, Gelman RS, et al. Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial. J Clin Oncol. 2005;23:1934–1940
  68. Hardenbergh PH, Recht A, Gollamudi S, et al. Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer. Int J Radiat Oncol Biol Phys. 1999;45:69–72
  69. Calais G. Radiation and concomitant chemotherapy after surgery for breast cancer. Cancer Radiother. 2004;8:39–47
  70. Rouesse J, Cvitkovic F, De Lalande B, et al. Concomitant or sequential chemo-radiotherapy (CRT) in operable breast cancer. Final results of a French multicentric phase III study. [abstract 649] Breast Cancer Res Treat. 2002;76(suppl 1):S160
  71. Calais G, Serin D, Fourquet A, et al. Randomized study comparing adjuvant radiotherapy (RT) with concomitant chemotherapy (CT) versus sequential treatment after conservative surgery for patients with stages I and II breast carcinoma. Int J Radiat Oncol Biol Phys. 2002;54:57–58
  72. Park CC, Mitsumori M, Nixon A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol. 2000;18:1668–1675

PII: S0936-6555(05)00446-2

doi: 10.1016/j.clon.2005.11.010

Clinical Oncology
Volume 18, Issue 3 , Pages 247-256 , April 2006

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