Postoperative Radiotherapy in High-Risk Premenopausal Women with Breast Cancer Who Receive Adjuvant Chemotherapy
Marie Overgaard, M.D., Per S. Hansen, M.D., Jens Overgaard, M.D., Carsten Rose, M.D., Michael Andersson, M.D., Flemming Bach, M.D., Mogens Kjaer, M.D., Carl C. Gadeberg, M.D., Henning T. Mouridsen, M.D., Maj-Britt Jensen, M.Sc., Karin Zedeler, M.Sc., for The Danish Breast Cancer Cooperative Group 82b Trial
Background Irradiation after mastectomy can reduce locoregionalrecurrences in women with breast cancer, but whether it prolongssurvival remains controversial. We conducted a randomized trialof radiotherapy after mastectomy in high-risk premenopausalwomen, all of whom also received adjuvant systemic chemotherapywith cyclophosphamide, methotrexate, and fluorouracil (CMF).
Methods A total of 1708 women who had undergone mastectomy forpathological stage II or III breast cancer were randomly assignedto receive eight cycles of CMF plus irradiation of the chestwall and regional lymph nodes (852 women) or nine cycles ofCMF alone (856 women). The median length of follow-up was 114months. The end points were locoregional recurrence, distantmetastases, disease-free survival, and overall survival.
Results The frequency of locoregional recurrence alone or withdistant metastases was 9 percent among the women who receivedradiotherapy plus CMF and 32 percent among those who receivedCMF alone (P<0.001). The probability of survival free ofdisease after 10 years was 48 percent among the women assignedto radiotherapy plus CMF and 34 percent among those treatedonly with CMF (P<0.001). Overall survival at 10 years was54 percent among those given radiotherapy and CMF and 45 percentamong those who received CMF alone (P<0.001). Multivariateanalysis demonstrated that irradiation after mastectomy significantlyimproved disease-free survival and overall survival, irrespectiveof tumor size, the number of positive nodes, or the histopathologicalgrade.
Conclusions The addition of postoperative irradiation to mastectomyand adjuvant chemotherapy reduces locoregional recurrences andprolongs survival in high-risk premenopausal women with breastcancer.
Source Information
From the Department of Oncology, Aarhus University Hospital, Aarhus (M.O.); the Department of Medicine, Viborg County Hospital, Viborg (P.S.H.); the Danish Cancer Society and the Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus (J.O.); the Department of Oncology, Odense University Hospital, Odense (C.R.); the Department of Oncology, Rigshospitalet, Copenhagen (M.A., H.T.M.); the Department of Oncology, Copenhagen University Hospital, Herlev (F.B.); the Department of Oncology, Aalborg County Hospital, Aalborg (M.K.); the Department of Oncology, Vejle County Hospital, Vejle (C.C.G.); and the Danish Breast Cancer Cooperative Group Secretariat, Rigshospitalet, Copenhagen (H.T.M., M.-B.J., K.Z.) — all in Denmark.
Address reprint requests to Dr. Overgaard at the Department of Oncology, Aarhus University Hospital, Nørrebrogade 44, Bldg. 5, DK-8000 Aarhus C, Denmark.
Radiotherapy and Chemotherapy in High-Risk Breast Cancer
El-Tamer M., Homel P., Braverman A. S., Wolberg W. H., Robins H. I., Goldhirsch A., Coates A. S., Colleoni M., Gelber R. D., Raffle A.E., Evans R. A., Overgaard M., Rose C., Mouridsen H., Ragaz J., Jackson S. M., Spinelli J. J., Hellman S.
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N Engl J Med 1998;
338:329-333, Jan 29, 1998.
Correspondence
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(2003). Diminished Survival in Patients With Inner Versus Outer Quadrant Breast Cancers. JCO
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Guenther, J. M., Hansen, N. M., DiFronzo, L. A., Giuliano, A. E., Collins, J. C., Grube, B. L., O'Connell, T. X.
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Buchholz, T. A., Strom, E. A., Perkins, G. H., McNeese, M. D.
(2002). Controversies Regarding the Use of Radiation After Mastectomy in Breast Cancer. The Oncologist
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Buchholz, T. A., Kronowitz, S. J., Kuerer, H. M.
(2002). Immediate Breast Reconstruction after Skin-Sparing Mastectomy for the Treatment of Advanced Breast Cancer: Radiation Oncology Considerations. Ann. Surg. Oncol.
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Chen, H. H. W., Su, W.-C., Guo, H.-R., Chang, T.-W., Lee, W.-Y.
(2002). p53 and c-erbB-2 but Not bcl-2 are Predictive of Metastasis-free Survival in Breast Cancer Patients Receiving Post-mastectomy Adjuvant Radiotherapy in Taiwan. Jpn J Clin Oncol
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Fisher, B., Jeong, J.-H., Anderson, S., Bryant, J., Fisher, E. R., Wolmark, N.
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Stathopoulou, A., Vlachonikolis, I., Mavroudis, D., Perraki, M., Kouroussis, Ch., Apostolaki, S., Malamos, N., Kakolyris, S., Kotsakis, A., Xenidis, N., Reppa, D., Georgoulias, V.
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Nieto, Y., Nawaz, S., Jones, R. B., Shpall, E. J., Cagnoni, P. J., McSweeney, P. A., Baron, A., Razook, C., Matthes, S., Bearman, S. I.
(2002). Prognostic Model for Relapse After High-Dose Chemotherapy With Autologous Stem-Cell Transplantation for Stage IV Oligometastatic Breast Cancer. JCO
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Leonard, R., Hardy, J., van Tienhoven, G., Houston, S., Simmonds, P., David, M., Mansi, J.
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