570 age on estimated survival probability using the various deﬁnitions of survival. As shown in Table 4, patients aged more than 70 years were at risk for dying from a cause unrelated to breast cancer, whereas patients aged 50 years or less seldom died from a cause unrelated to breast cancer. As a consequence, in the younger subgroup 10-year overall survival was almost equal to 10-year disease speciﬁc sur- vival. Whereas in the elderly, estimated 10-year disease speciﬁc survival was more than 30% point better than estimated 10-year overall survival (Fig. 1). In the younger subgroups differences between Kaplan–Meier and com- peting risk estimates were limited (£1%). In the elderly estimations of 10-year disease speciﬁc survival were 82.2% and 84.9% with Kaplan–Meier and competing risk analy- ses, respectively. Estimations of 10-year disease free interval were 73.6% and 77.6% respectively for two sta- tistical methods. Contralateral breast cancer We evaluated the effect of the inclusion of contralateral breast cancer as event in the analysis of disease recurrence on estimated disease free interval and disease free survival (Table 3). The administration of adjuvant systemic therapy is known to reduce the risk of contralateral breast cancer [12, 13]. In the whole study population the absolute reduction in disease free survival or disease free interval due to inclusion of contralateral breast cancer as event in the deﬁnition of relapse was approximately 4%; in patients not treated with adjuvant systemic therapy 6–7%, and in patients treated with adjuvant systemic therapy 1–2%. In the broadest deﬁnition of relapse 197 events were counted during 10-years follow-up, including 47 non-disease re- lated deaths and 26 contralateral breast cancers. That is, in the analysis of disease free interval 17% of events were contralateral breast cancers, compared with 13% in the analysis of disease free survival. Consequently, the effect of the inclusion of contralateral breast cancer as event in Breast Cancer Res Treat (2008) 109:567–572 the deﬁnition of relapse was greater when estimating dis- ease free interval than when estimating disease free sur- vival (Table 3). Similarly, the greatest effect of the inclusion of contra- lateral breast cancer and non-disease related death as events on estimated disease recurrence rate was found in patients with low risk breast cancer. In a subgroup of 168 patients with T1N0 breast cancer, not treated with adjuvant systemic therapy, the 10-year relapse rate including local relapse, regional relapse, or distant metastasis was 23%. The estimated 10-year relapse rate rose to 31% both with the inclusion of either contralateral breast cancer or non- disease related death as event in the deﬁnition of relapse, and to 38% with the inclusion of both events in the deﬁ- nition of relapse. Discussion In the present study we show that the inclusion of contra- lateral breast cancer or non-disease related death as event in the deﬁnition of recurrent disease or survival of early breast cancer signiﬁcantly affects estimated outcome probability. The magnitude of the effect depends on pa- tient-, tumour-, and treatment characteristics. The greatest effect was observed for the handling of non-disease related death within the group of patients older than 70 years, and for the inclusion of contralateral breast cancer as event in patients with low risk breast cancer not treated with adju- vant systemic therapy. These ﬁndings stress the importance of a clear deﬁnition and reporting of outcome parameters in scientiﬁc papers presenting the results of phase III randomized trials. However, the magnitude of the observed effects can differ depending on the various events that have been included, ignored or censored in the deﬁnition of outcome. As a consequence, the in- or exclusion of contralateral breast cancer or non-disease related death in the deﬁnition of Table 4 Estimated 10-year event rate according to age at diagnosis determined both by Kaplan–Meier method and competing risk analysis. 10-year Event rate (%) £ 50 yr KM 31.1 28.6 3.6 41.5 39.5 3.2 CR 28.1 3.0 38.8 2.7 51–70 yr KM 23.5 16.4 8.5 32.2 26.8 7.5 CR 15.7 7.8 25.8 6.5 > 70 yr KM 52.0 17.7 41.7 58.7 26.3 43.8 CR 15.1 36.9 22.4 36.2 Event Overall death Disease related death Non-disease related death Recurrent disease or death Recurrent disease Death without recurrent disease 123 KM: Kaplan–Meier method; CR: competing risk analysis. Recurrent disease was deﬁned as either local recurrence, regional recurrence or distant metastasis whichever came ﬁrst. Occurring contralateral breast cancer was ignored