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

BACKGROUND: Assessment of Ki67 by immunohistochemistry (IHC) has limited utility in clinical practice owing to analytical validity issues. According to International Ki67 Working Group (IKWG) guidelines, treatment should be guided by a prognostic test in patients expressing intermediate Ki67 range, >5%-<30%. The objective of the study is to compare the prognostic performance of CanAssist Breast (CAB) with that of Ki67 across various Ki67 prognostic groups. METHODS: The cohort had 1701 patients. Various risk groups were compared for the distant relapse-free interval (DRFi) derived from Kaplan-Meier survival analysis. As per IKWG, patients are categorized into three risk groups: low-risk (<5%), intermediate risk (>5%-<30%), and high-risk (>30%). CAB generates two risk groups, low and high risk based on a predefined cutoff. RESULTS: In the total cohort, 76% of the patients were low risk (LR) by CAB as against 46% by Ki67 with a similar DRFi of 94%. In the node-negative sub-cohort, 87% were LR by CAB with a DRFi of 97% against 49% by Ki67 with a DRFi of 96%. In subgroups of patients with T1 or N1 or G2 tumors, Ki67-based risk stratification was not significant while it was significant by CAB. In the intermediate Ki67 (>5%-<30%) category up to 89% (N0 sub-cohort) were LR by CAB and the percentage of LR patients was 25% (p < 0.0001) higher compared to NPI or mAOL. In the low Ki67 (≤5%) group, up to 19% were segregated as high-risk by CAB with 86% DRFi suggesting the requirement of chemotherapy in these low Ki67 patients. CONCLUSION: CAB provided superior prognostic information in various Ki67 subgroups, especially in the intermediate Ki67 group.

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

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.