Open AccessClinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
Author(s) -
Bakre Manjiri M.,
Ramkumar Charusheila,
Attuluri Arun Kumar,
Basavaraj Chetana,
Prakash Chandra,
Buturovic Ljubomir,
Madhav Lekshmi,
Naidu Nirupama,
R Prathima,
Somashekhar S. P.,
Gupta Sudeep,
Doval Dinesh Chandra,
Pegram Mark D.
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2049
Subject(s) - medicine , breast cancer , hazard ratio , oncology , immunohistochemistry , multivariate analysis , cohort , proportional hazards model , retrospective cohort study , cancer , confidence interval
Abstract CanAssist‐Breast ( CAB ) is an immunohistochemistry ( IHC )‐based prognostic test for early‐stage Hormone Receptor ( HR +)‐positive breast cancer patients. CAB uses a Support Vector Machine ( SVM ) trained algorithm which utilizes expression levels of five biomarkers ( CD 44, ABCC 4, ABCC 11, N‐Cadherin, and Pan‐Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low‐ or high‐risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB . CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis‐Free Survival ( DMFS ) and recurrence rates using Kaplan‐Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios ( HR ) for CAB high‐risk vs low‐risk patients. The results showed that Distant Metastasis‐Free Survival ( DMFS ) was significantly different ( P ‐0.002) between low‐ ( DMFS : 95%) and high‐risk ( DMFS : 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low‐risk DMFS : 95%, high‐risk DMFS : 84%, P < 0.0001). In addition, the segregation of the risk categories was significant ( P = 0.0005) in node‐positive patients, with a difference in DMFS of 12%. In multivariate analysis, CAB risk score was the most significant predictor of distant recurrence with hazard ratio of 3.2048 ( P < 0.0001). CAB stratified patients into discrete risk categories with high statistical significance compared to Ki‐67 and IHC 4 score‐based stratification. CAB stratified a higher percentage of the cohort (82%) as low‐risk than IHC 4 score (41.6%) and could re‐stratify >74% of high Ki‐67 and IHC 4 score intermediate‐risk zone patients into low‐risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high‐ or low‐risk categorization.