Originally published as JCO Early Release 10.1200/JCO.2008.21.5764 on August 31 2009

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Impact of Pathological Characteristics on Local Relapse After Breast-Conserving Therapy: A Subgroup Analysis of the EORTC Boost Versus No Boost Trial

Heather A. Jones, Ninja Antonini, Augustinus A.M. Hart, Johannes L. Peterse, Jean-Claude Horiot, Françoise Collin, Philip M. Poortmans, S. Bing Oei, Laurence Collette, Henk Struikmans, Walter F. Van den Bogaert, Alain Fourquet, Jos J. Jager, Dominic A.X. Schinagl, Carla C. Wárlám-Rodenhuis, Harry Bartelink

From the Department of Radiation Oncology, the University of Pittsburgh Cancer Center, Pittsburgh, PA; Departments of Radiation Oncology and Pathology, The Netherlands Cancer Institute/Antoni Van Leeuwenhoekhuis, Amsterdam; Department of Radiation Oncology, Dr Bernard Verbeeten Instituut, Tilburg; Department of Radiation Oncology, University Medical Centre. Leiden; Department of Radiation Oncology, Maastricht Radiation Oncology Clinic, Maastricht; Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen; Department of Radiation Oncology, University Medical Centre, Utrecht, the Netherlands; Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon; Department of Radiation Oncology, Institute Curie, Paris, France; European Organisation for Research and Treatment of Cancer Headquarters, Brussels; and the Department of Radiation Oncology, University Hospital Gasthuisberg, Leuven, Belgium.

Corresponding author: Harry Bartelink, MD, PhD, Department of Radiation Oncology, the Netherlands Cancer Institute/Antoni Van Leeuwenhoekhuis, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: h.bartelink{at}nki.nl.

Purpose To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT).

Patients and Methods In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.

Results The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively.

Conclusion Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.

Deceased.

H.A.J. and N.A. contributed equally to this article.

European Organisation for Research and Treatment of Cancer was supported by Grants No. 5R10-CA11488-11 through 5U10-CA11488-38 from the National Cancer Institute (Bethesda, MD) for conducting trial 22881/10882.

The contents of this article are solely the responsibility of the authors and do not necessarily reflect the official views of the National Cancer Institute.

Written on behalf of the European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

See accompanying editorial on page 4929

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