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Annals of Oncology Advance Access published online on March 15, 2008
Annals of Oncology, doi:10.1093/annonc/mdn029
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study

Y. Belkacémi1,2,*, J. Gligorov3, M. Ozsahin4,5, H. Marsiglia6,7, B. De Lafontan8, H. Laharie-Mineur9, L. Aimard10, E.-C. Antoine11, B. Cutuli12, M. Namer13 and D. Azria14

1 Department of Radiation Oncology, CLCC Oscar Lambret Anti-Cancer Center
2 University of Lille II, Lille
3 Department of Medical Oncology APHP Tenon, Cancer Est, Paris, France
4 Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois
5 University of Lausanne, Lausanne, Switzerland
6 Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
7 Florence University, Florence, Italy
8 Department of Radiation Oncology, Institut Claudius Regaud, Toulouse
9 Department of Radiation Oncology, Institut Bergonié, Bordeaux
10 Clairval Clinic, Marseille
11 Hartmann Clinic, Neuilly sur Seine
12 Courlancy Polyclinic, Reims
13 Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins
14 Department of Radiation Oncology, Institut National de la Santé et de la Recherche Médicale, Montpellier, France

* Correspondence to: Dr Y. Belkacémi, Department of Radiation Oncology, CLCC Oscar Lambret Anti-Cancer Center, 3 rue Frédéric Combemale, Lille 59020, France. Tel: +33-3-20-29-59-59; Fax: +33-3-20-29-59-72; E-mail: y-belkacemi{at}o-lambret.fr

Background: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting.

Patients and methods: Data of 146 patients with stages II–III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients.

Results: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade ≥2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity.

Conclusion: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.

acute toxicity, breast cancer, LVEF, radiation therapy, targeted therapies, trastuzumab

Received for publication August 29, 2007. Revision received January 14, 2008. Accepted for publication January 15, 2008.


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