Half of the distant recurrences (DR) occur after the first five years from diagnosis. The Clinical Treatment Score post-5 years (CTS5) intends to predict DR after 5 years of endocrine therapy (ET). This study uses the IDEAL study cohort, consisting of patients disease free after 5 years of standard adjuvant ET and randomized between 2.5 or 5 years of extended therapy with letrozole, to validate the CTS5 as a prognostic tool for late DR and, if it is validated, to examine it as a predictive tool for choosing between 2.5 years or 5 years of extended ET.
The CTS5 categorizes patients that had been disease free for 5 years, into low (<5%), intermediate (5-10%) and high (>10%) risk groups for developing DR between 5 and 10 years after diagnosis. To validate the CTS5, both the discrimination and calibration are examined.
In this analysis, 1591 patients from the IDEAL study cohort were included. Overall, they were younger, had more lymph node involvement, higher grade tumours and received more chemotherapy than patients in the ATAC and 1BIG 1-98 cohorts used to train and test the CTS5. Consequently, more patients were allocated to the high risk group than in the training and testing cohort. For the prognostic value of the CTS5 score, we showed that there were significantly more DR between 5 and 10 years after diagnosis in the high risk group (HR 4.9, 95% CI 2.3-10.1) and the intermediate risk group (HR 2.2, 95% CI 1.03-4.8) compared to the low risk group (log-rank p < 0.001). The expected risk scores for the low, intermediate and high risk groups, calculated using the CTS5 scores, were 3.6%, 7.2% and 19.4%, respectively. The observed late DR using K-M curves were 1.4% (95% CI 0.7-2.1), 5.6% (4.7-6.5) and 10.6% (9.4-11.8) for the low, intermediate and high risk groups, respectively. The CTS5 risk score systematically overestimates the risk of late DR. Since the algorithm could not be validated, it was not deemed relevant to examine its predictive abilities for extended ET within the risk groups.
The CTS5 is able to significantly discriminate patients into three different risk categories. However, the calibration could not be validated, as the absolute risk for DR was significantly lower than the expected DR. The CTS5 should therefore not be used as prognostic tool for distant breast cancer recurrences.
BOOG 2006-05.
CJH van de Velde.
The original IDEAL trial was supported by Novartis by means of an independent educational grant (CFEM345DNL03). This IDEAL substudy received no additional funding.
All authors have declared no conflicts of interest.