Breast Cancer Res Treat (2008) 109:567–572 DOI 10.1007/s10549-007-9681-x E P I D E M I O L O G Y The in- or exclusion of non-breast cancer related death and contralateral breast cancer signiﬁcantly affects estimated outcome probability in early breast cancer R. A. Nout Æ W. E. Fiets Æ H. Struikmans Æ F. R. Rosendaal Æ H. Putter Æ J. W. R. Nortier Received: 27 June 2007 / Accepted: 9 July 2007 / Published online: 28 July 2007 Springer Science+Business Media B.V. 2007 Abstract A wide variation of deﬁnitions of recurrent disease and survival are used in the analyses of outcome of patients with early breast cancer. Explicit deﬁnitions with details both on endpoints and censoring are provided in less than half of published studies. We evaluated the effects of various deﬁnitions of survival and recurrent disease on estimated outcome in a prospectively determined cohort of 463 patients with primary breast cancer. Outcome esti- mates were determined both by the Kaplan–Meier and a competing risk method. In- or exclusion of contralateral breast cancer or non-disease related death in the deﬁnition of recurrent disease or survival signiﬁcantly affects esti- mated outcome probability. The magnitude of this ﬁnding was dependent on patient-, tumour-, and treatment char- acteristics. Knowledge of the contribution of non-disease related death or contralateral breast cancer to estimated R. A. Nout (&) J. W. R. Nortier Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands e-mail: r.a.nout@lumc.nl W. E. Fiets Department of Internal Medicin, Medical Center Leeuwarden, Leeuwarden, The Netherlands H. Struikmans Department of Radiation Oncology, Haaglanden Medical Center, The Hague, The Netherlands F. R. Rosendaal Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands H. Putter Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands recurrent disease rate and overall death rate is indispens- able for a correct interpretation and comparison of outcome analyses. Keywords Breast cancer End-points Prognosis Study design Survival analysis Introduction In studies on early breast cancer, outcome is usually de- ﬁned as the time from diagnosis or surgery until a partic- ular event of interest (endpoint). The event of interest can vary and may include death (overall survival), disease re- lated death (disease speciﬁc survival), or recurrent disease (disease free survival). Altman et al. systematically reviewed the appropriate- ness of the application and presentation of survival analysis in clinical oncology journals [1]. They found that among papers speciﬁcally dealing with death as an end- point; only 47% explicitly described this end-point as either any death or only cancer-related death. In as much as 61% of papers that studied time to progressive disease the handling of non-cancer related mortality was not clearly deﬁned. In studies on patients with early breast cancer a wide variation of deﬁnitions of disease free survival have been used. These deﬁnitions always included local recurrence, regional recurrence, and distant metastasis, but some- times also included non-disease related death, contralat- eral breast cancer and in some cases second primary cancer. For example, the 1998 overview of randomised trials on adjuvant therapy included contralateral breast cancer in the analysis of disease recurrence, but did not include non-disease related death [2]. In the NSABP B14 123