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Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine
Karama Asleh1,2, Ana Lluch3,4,5, Angela Goytain1
1Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada.
Summary
The PAM50 non-basal molecular subtype is a key predictor of capecitabine benefit in triple-negative breast cancer (TNBC). This finding validates previous research and identifies patients most likely to respond to this treatment.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating predictive biomarkers for treatment selection.
- Previous studies identified potential biomarkers, including non-basal phenotype and angiogenesis-related genes, for capecitabine benefit in TNBC.
Purpose of the Study:
- To validate previously proposed predictive biomarkers for capecitabine benefit in a larger cohort of TNBC patients.
- To assess the predictive capacity of the PAM50 non-basal molecular subtype and other gene expression patterns for capecitabine efficacy.
Main Methods:
- Analysis of tumor tissues from 658 evaluable patients with TNBC from the phase III GEICAM/CIBOMA clinical trial.
- Utilized a 164-gene NanoString custom nCounter codeset to measure mRNA expression.
- Prespecified statistical analysis to evaluate the PAM50 non-basal subtype and specific gene expression signatures as predictors of distant recurrence-free survival and overall survival.
Main Results:
- The PAM50 non-basal subtype was a significant predictor of capecitabine benefit (HR=0.19, P<0.001), while the basal-like subtype showed no benefit (HR=0.9, P=0.55).
- The non-basal subtype was enriched for pathways including mast cells, extracellular matrix, and angiogenesis.
- An interaction P-value <0.001 (adjusted P=0.01) confirmed the significance of PAM50 non-basal status in predicting capecitabine response.
Conclusions:
- PAM50 non-basal status is a validated predictive biomarker for capecitabine benefit in early-stage TNBC patients.
- This finding aids in personalizing adjuvant capecitabine treatment for TNBC, improving patient outcomes.
