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Journal of Clinical Oncology, Vol 25, No 36 (December 20), 2007: pp. 5841 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.6910
What Is the Impact of Tamoxifen on Radiation-Induced Fibrosis in Patients Receiving Breast-Conserving TherapyDepartment of Radiation Oncology, Ataturk University Medical School, Erzurum, Turkey To The Editor: Bartelink et al1 reported the impact of higher radiation dose on local control and survival in patients who underwent breast conservation therapy for early breast cancer. They used 10-year results of the randomized boost versus no boost European Organisation for Research and Treatment of Cancer 22881-10882 trial. A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years. The major purpose of this report was to find out the long-term impact of a boost irradiation of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy. They reported that severe fibrosis was statistically significantly increased in the boost group, with a 10-year rate of 4.4% v 1.6% in the no-boost group. It is well known in the literature that higher radiation doses significantly increase severe fibrosis that resulted in poor cosmetic results.2,3 However, in Bartelink et al,1 there is no information about the percentage of patients within the boost or no-boost group that received tamoxifen (TAM) treatment. In addition, the differences between TAM treatment versus no TAM treatment in the boost group must be explained (if any). Apart from its (anti)hormonal properties, TAM also has a number of nonhormonal effects. The induction of transforming growth factor β (TGF-β) is one of the documented nonhormonal effects of TAM.4 It generally inhibits the growth of epithelial cells, but induces chemotaxis of fibroblasts. This may explain the importance of TGF-β in the pathogenesis of fibrosis in a large number of animal models and human disorders.5-7 Nonhormonal effects of TAM can cause fibrosis of liver, skin, muscle, lungs, and mammary gland, most likely by the induction of TGF-β secretion. Johansen et al8 also recently reported that TAM was significantly associated with breast fibrosis. I believe that in the article by Bartelink et al,1 if the impact of TAM on fibrosis were analyzed in subgroups of boost versus no-boost groups in a study with a large sample size (ie, 5,318 patients) and 10-year period, the contribution to the literature would be enormous. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Bartelink H, Horiot JC, Poortmans PM, et al: Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 25:3259-3265, 2007 2. Huang EY, Wang CJ, Chen HC, et al: Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics for non-dosimetric factors. Radiother Oncol 57:91-96, 2000[CrossRef][Medline] 3. Alexander MAR, Brooks WA, Blake SW: Normal tissue complication probability modelling of tissue fibrosis following breast radiotherapy. Phys Med Biol 52:1831-1843, 2007[CrossRef][Medline] 4. Bentzen SM, Overgaard M: Clinical radiobiology and normal tissue morbidity after breast cancer treatment, in Altman KI, Lett JT (eds): Advances in Radiation Biology (Vol 18). San Diego, CA, Academic Press, 1994, pp 25-51 5. Border WA, Noble NA: Transforming growth factor beta in tissue fibrosis. N Engl J Med 331:1286-1292, 1994 6. Butta A, Mac Lennan K, Flanders KC, et al: Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res 52:4261-4264, 1992 7. Colletta AA, Wakefield LM, Howell FV, et al: Anti-estrogen induce the secretion of active transforming growth factor beta from human fetal fibroblasts. Br J Cancer 62:405-409, 1990[Medline] 8. Johansen J, Overgaard J, Overgaard M: Effect of adjuvant systemic treatment on cosmetic outcome and late normal-tissue reactions after breast conservation. Acta Oncol 46:525-533, 2007[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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