Analytical validation of CanAssist-Breast: an immunohistochemistry based prognostic test for hormone receptor positive breast cancer patients

Abstract

BackgroundCanAssist-Breast is an immunohistochemistry based test that predicts risk of distant recurrence in early-stage hormone receptor positive breast cancer patients within first five years of diagnosis. Immunohistochemistry gradings for 5 biomarkers (CD44, ABCC4, ABCC11, N-Cadherin and pan-Cadherins) and 3 clinical parameters (tumor size, tumor grade and node status) of 298 patient cohort were used to develop a machine learning based statistical algorithm. The algorithm generates a risk score based on which patients are stratified into two groups, low- or high-risk for recurrence. The aim of the current study is to demonstrate the analytical performance with respect to repeatability and reproducibility of CanAssist-Breast.MethodsAll potential sources of variation in CanAssist-Breast testing involving operator, run and observer that could affect the immunohistochemistry performance were tested using appropriate statistical analysis methods for each of the CanAssist-Breast biomarkers using a total 309 samples. The cumulative effect of these variations in the immunohistochemistry gradings on the generation of CanAssist-Breast risk score and risk category were also evaluated. Intra-class Correlation Coefficient, Bland Altman plots and pair-wise agreement were performed to establish concordance on IHC gradings, risk score and risk categorization respectively.ResultsCanAssist-Breast test exhibited high levels of concordance on immunohistochemistry gradings for all biomarkers with Intra-class Correlation Coefficient of ≥0.75 across all reproducibility and repeatability experiments. Bland-Altman plots demonstrated that agreement on risk scores between the comparators was within acceptable limits. We also observed > 90% agreement on risk categorization (low- or high-risk) across all variables tested.ConclusionsThe extensive analytical validation data for the CanAssist-Breast test, evaluating immunohistochemistry performance, risk score generation and risk categorization showed excellent agreement across variables, demonstrating that the test is robust.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5443-5) contains supplementary material, which is available to authorized users.

Comparison of breast cancer prognostic tests CanAssist Breast and Oncotype DX

“…CanAssist Breast was developed as an affordable alternative to expensive multigene prognostic tests for early stage HR+ breast cancer, particularly in developing countries in Asia 17‐19,26 . The test was developed on Indian patients, and has since been validated in patients from India and United States 17,19 .…”

“…While CAB was developed for both node negative and node positive patients, 17‐19 ODX was initially developed on node negative breast cancer patients and the TAILORx study also focused on node negative patients 12,25 . As noted above, the website of Exact Sciences/Oncotype IQ recommends ODX with TAILORx cut‐offs for breast cancer patients up to Stage IIIA 36 .…”

“…A number of available prognostic tests predict risk of recurrence for early stage HR+ breast cancer based on multigene expression (Oncotype DX [ODX], MammaPrint, Breast Cancer Index), or a combination of multigene expression and clinical parameters (Prosigna, EndoPredict‐EPclin, CanAssist Breast [CAB]) 12‐19 …”

“…CanAssist Breast combines the immunohistochemistry (IHC) data of five biomarkers with three clinical parameters (tumor size, grade, and node status) with a machine learning‐based statistical algorithm to calculate a risk score. CAB thus stratifies early stage HR+ HER2− breast cancer patients into low‐risk or high‐risk for distant recurrence 17‐19 . CAB has been retrospectively validated in a mixed cohort of Asian and Caucasian patients and is being used by clinicians in India 19,26 …”

CanAssist Breast Impacting Clinical Treatment Decisions in Early-Stage HR+ Breast Cancer Patients: Indian Scenario

“…Of all these tests, CAB is the only test that has been developed and validated on a mixed cohort of Asian (Indian) and Caucasian patients in a 3:1 proportion [15] and extensively validated for analytical performance [16]. CAB is an immunohistochemistry (IHC)based test that assesses risk of cancer recurrence at a distant site within 5 years from diagnosis.…”