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Journal of Clinical Oncology, Vol 26, No 6 (February 20), 2008: pp. 1014-a-1015 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.1860
Patients With Breast Cancer Are Unlikely to Benefit From Prophylactic Irradiation of the Contralateral BreastGynecological Oncology, University of Turin, Institute for Cancer Research and Treatment of Candiolo, Turin, Italy To the Editor: Brenner et al1 suggest a potential role for prophylactic mammary irradiation (PMI) to reduce both ipsilateral and contralateral second cancers in patients with breast cancer. For a patient treated at 57 years of age, the authors calculated cumulative 20-year risks of radiation-induced second breast cancers in the ipsilateral and contralateral breast of 14% and 2%, respectively, and corresponding risks of second breast cancers due to enhanced genetic susceptibility of 12% and 14%, respectively. We found these figures rather high for women of postmenopausal age, considering that the estimated radiation and genetic background risks are strongly influenced by the age of the patient. In postmenopause, sensitivity to the carcinogenic effect of radiotherapy is low and most breast cancers are sporadic, while in the younger women, both the risk of radiation-induced cancers (as demonstrated for Hodgkin's disease)2 and the percentage of BRCA1/2-related cancers (and thus the genetic risk of ipsilateral and contralateral second cancers)3 are much higher. Nevertheless, even accepting these high figures, it is mandatory that any risk should be put into perspective and considered together with the other competing risks.4 The prevention of ipsilateral second breast cancer events, either represented by true recurrences or second primaries, may indeed prolong the overall survival of patients with breast cancer.5 Nevertheless, this effect is likely to be small given that no survival difference has ever been reported in single studies comparing breast-conserving surgery plus radiotherapy versus mastectomy.6 Although no definitive conclusion can be drawn on the efficacy of partial-breast irradiation after breast-preserving surgery, preliminary results are encouraging,7 and some data suggest that elderly postmenopausal women may even avoid radiotherapy at all.8 Therefore, we agree with the authors that the administration of a full, accelerated dose of radiotherapy to the tumor bed and a lower dose to the remaining breast seems to be a treatment strategy worthy of pursuit in the context of a clinical trial. Conversely, we do not believe that PMI of the contralateral breast is likely to offer any substantial benefit to patients with breast cancer. For older patients whose life expectancy is lower and the rate of comorbidities is higher, the risk/benefit ratio of such an intervention may be substantially altered or even reversed by treatment-associated toxicities. On the other hand, the risk of death from the primary tumor will variably dominate the survival chances of a patient depending on her age (increasing influence with decreasing age) and stage of disease (increasing influence with advancing stage). Therefore, ironically, young patients with a BRCA1/2 mutation, who would be expected to be ideal candidate for contralateral PMI, may actually gain little from it. In fact, these women carry the highest a priori risk of developing a second cancer, but often they have been already diagnosed with aggressive, node-positive, non–endocrine-sensitive tumors. Therefore, their prognosis may remain unfavorable despite optimal treatments, and no real benefit can reasonably be expected from contralateral PMI, considering that even contralateral prophylactic mastectomy, which is associated with the highest protection, does not seem to provide any survival gain.9,10 AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Brenner DJ, Shuryak I, Russo S, et al: Reducing second breast cancers: A potential role for prophylactic mammary irradiation. J Clin Oncol 25:4868-4872, 2007 2. Travis LB, Hill D, Dores GM, et al: Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J Natl Cancer Inst 97:1428-1437, 2005 3. Chen S, Parmigiani G: Meta-Analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329-1333, 2007 4. Bunker JP, Houghton J, Baum M: Putting the risk of breast cancer in perspective. BMJ 317:1307-1309, 1998 5. 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 366:2087-2106, 2005[Medline] 6. Veronesi U, Cascinelli N, Mariani L, et al: Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227-1232, 2002 7. Chen PY, Vicini FA: Partial breast irradiation: Patient selection, guidelines for treatment, and current results. Front Radiat Ther Oncol 40:253-271, 2007[Medline] 8. Livi L, Paiar F, Meldolesi E, et al: The management of elderly patients with T1–T2 breast cancer treated with or without radiotherapy. Eur J Surg Oncol 31:473-478, 2005[CrossRef][Medline] 9. van Sprundel TC, Schmidt MK, Rookus MA, et al: Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 93:287-292, 2005[CrossRef][Medline] 10. Tilanus-Linthorst MM, Alves C, Seynaeve C, et al: Contralateral recurrence and prognostic factors in familial non-BRCA1/2-associated breast cancer. Br J Surg 93:961-968, 2006[CrossRef][Medline] Related Reply
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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