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Supplementary Figure S1 from Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine

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posted on 2023-04-01, 00:02 authored by Karama Asleh, Ana Lluch, Angela Goytain, Carlos Barrios, Xue Q. Wang, Laura Torrecillas, Dongxia Gao, Manuel Ruiz-Borrego, Samuel Leung, José Bines, Ángel Guerrero-Zotano, Jose Ángel García-Sáenz, Juan Miguel Cejalvo, Jesus Herranz, Roberto Torres, Juan de la Haba-Rodriguez, Francisco Ayala, Henry Gómez, Federico Rojo, Torsten O. Nielsen, Miguel Martin

Supplementary Figure S1 shows the expression of the 50 genes in the PAM50 signature, obtained from the 164-gene codeset.

Funding

Canadian Cancer Society Research Institute (CCSRI)

Canadian Institutes of Health Research (IRSC)

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ARTICLE ABSTRACT

Predictive biomarkers for capecitabine benefit in triple-negative breast cancer (TNBC) have been recently proposed using samples from phase III clinical trials, including non-basal phenotype and biomarkers related to angiogenesis, stroma, and capecitabine activation genes. We aimed to validate these findings on the larger phase III GEICAM/CIBOMA clinical trial. Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using a 164-gene NanoString custom nCounter codeset measuring mRNA expression. A prespecified statistical plan sought to verify the predictive capacity of PAM50 non-basal molecular subtype and tested the hypotheses that breast tumors with increased expression of (meta)genes for cytotoxic cells, mast cells, endothelial cells, PDL2, and 38 individual genes benefit from adjuvant capecitabine for distant recurrence-free survival (DRFS; primary endpoint) and overall survival. Of the 876 women enrolled in the GEICAM/CIBOMA trial, 658 (75%) were evaluable for analysis (337 with capecitabine and 321 without). Of these cases, 553 (84%) were profiled as PAM50 basal-like whereas 105 (16%) were PAM50 non-basal. Non-basal subtype was the most significant predictor for capecitabine benefit [HRcapecitabine, 0.19; 95% confidence interval (CI), 0.07–0.54; P < 0.001] when compared with PAM50 basal-like (HRcapecitabine, 0.9; 95% CI, 0.63–1.28; P = 0.55; Pinteraction<0.001, adjusted P value = 0.01). Analysis of biological processes related to PAM50 non-basal subtype revealed its enrichment for mast cells, extracellular matrix, angiogenesis, and features of mesenchymal stem-like TNBC subtype. In this prespecified correlative analysis of the GEICAM/CIBOMA trial, PAM50 non-basal status identified patients with early-stage TNBC most likely to benefit from capecitabine.

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