Retrospective analysis to validate the CTS5 in patients from El Álamo IV registry and GEICAM adjuvant studies

Identifying high-risk of late recurrence (beyond 10 years) in patients with hormone receptor-positive HER2-negative early breast cancer (EBC) is crucial. The Clinical Treatment Score post-5 years (CTS5) score assesses recurrence risk after 5 years of endocrine therapy (ET). This study validated CTS5 as a prognostic tool for late recurrence by examining its association with Distant Recurrence-Free Survival using GEICAM study data and evaluating model calibration.

We retrospectively analyzed 5739 hormone receptor-positive HER2-negative EBC patients from the El Álamo IV registry (N = 3509, diagnosed between 2002 and 2005) and 4 adjuvant GEICAM studies (N = 2680, conducted between 1996 and 2006). All patients were distant recurrence-free and alive 5 years after starting adjuvant ET.

The CTS5 classified 43.9% of patients as low-risk, 32.2% as intermediate-risk, and 23.9% as high-risk. Significant differences in DR were observed: hazard ratio (HR) for intermediate- vs. low-risk was 2.55 (95% CI, 1.85-3.51, P < .0001), and HR for high- vs. low-risk was 5.77 (95% CI, 4.28-7.78, P < .0001). Similar results were found across subgroups by menopausal status, duration of adjuvant ET, and prior adjuvant chemotherapy (CT). Calibration showed CTS5 overestimated DR rates in low-risk (P = .0314) and high-risk (P < .0001) patients compared to observed rates.

The CTS5 categorized patients based on late DR risk regardless of menopausal status, ET duration, or CT treatment. However, the model tended to overestimate events, particularly in high-risk groups, especially among those treated with ET for less than 60 months or not receiving CT.