Ten-year distant-recurrence risk prediction in breast cancer by CanAssist Breast (CAB) in Dutch sub-cohort of the randomized TEAM trial

Abstract

Background Hormone receptor (HR)-positive, HER2/neu-negative breast cancers have a sustained risk of recurrence up to 20 years from diagnosis. TEAM (Tamoxifen, Exemestane Adjuvant Multinational) is a large, multi-country, phase III trial that randomized 9776 women for the use of hormonal therapy. Of these 2754 were Dutch patients. The current study aims for the first time to correlate the ten-year clinical outcomes with predictions by CanAssist Breast (CAB)—a prognostic test developed in South East Asia, on a Dutch sub-cohort that participated in the TEAM. The total Dutch TEAM cohort and the current Dutch sub-cohort were almost similar with respect to patient age and tumor anatomical features. Methods Of the 2754 patients from the Netherlands, which are part of the original TEAM trial, 592 patients’ samples were available with Leiden University Medical Center (LUMC). The risk stratification of CAB was correlated with outcomes of patients using logistic regression approaches entailing Kaplan–Meier survival curves, univariate and multivariate cox-regression hazards model. We used hazard ratios (HRs), the cumulative incidence of distant metastasis/death due to breast cancer (DM), and distant recurrence-free interval (DRFi) for assessment. Results Out of 433 patients finally included, the majority, 68.4% had lymph node-positive disease, while only a minority received chemotherapy (20.8%) in addition to endocrine therapy. CAB stratified 67.5% of the total cohort as low-risk [DM = 11.5% (95% CI, 7.6–15.2)] and 32.5% as high-risk [DM = 30.2% (95% CI, 21.9–37.6)] with an HR of 2.90 (95% CI, 1.75–4.80; P < 0.001) at ten years. CAB risk score was an independent prognostic factor in the consideration of clinical parameters in multivariate analysis. At ten years, CAB high-risk had the worst DRFi of 69.8%, CAB low-risk in the exemestane monotherapy arm had the best DRFi of 92.7% [vs CAB high-risk, HR, 0.21 (95% CI, 0.11–0.43), P < 0.001], and CAB low-risk in the sequential arm had a DRFi of 84.2% [vs CAB high-risk, HR, 0.48 (95% CI, 0.28–0.82), P = 0.009]. Conclusions Cost-effective CAB is a statistically robust prognostic and predictive tool for ten-year DM for postmenopausal women with HR+/HER2−, early breast cancer. CAB low-risk patients who received exemestane monotherapy had an excellent ten-year DRFi.

Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method

“…While all the above mentioned tools use logistic regression, CanAssist Breast is an IHC based tool that uses an Artificial Intelligence-based Machine (SVM) algorithm for the prediction of recurrence risk with inputs from immunohistochemistry information of 5 critical biomarkers of cancer progression and recurrence pathways along with 3 clinical parameters [ 38 ]. CanAssist Breast has been validated in multiple cohorts from Southeast Asia, the USA and Europe [ 39 – 41 ] and in a DUTCH sub-cohort of TEAM trial- a prospective randomized trial [ 42 ]. The consensus guidelines state that CanAssist Breast and Oncotype DX are the recommended multi-marker prognostic tests that are the preferred choice (Table 2 ).…”

The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment

“…The limitations are a lack of comparative analysis of the intermediate Ki67 range with other prognostic tests like multigene tests and the retrospective nature of the study. Although we have recently shown validation of long‐term predictions (10 years) of CAB 28 , in a DUTCH sub‐cohort of a prospective trial, TEAM, validation of CAB in a prospective trial per se is the limitation for CAB.…”