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Predictive Biomarkers for Adjuvant Capecitabine Benefit in Early-Stage Triple-Negative Breast Cancer in the FinXX Clinical Trial

Asleh, Karama (författare)
Univ British Columbia, Genet Pathol Evaluat Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada.;Univ British Columbia, Interdisciplinary Oncol Program, Fac Med, Vancouver, BC, Canada.
Brauer, Heather Ann (författare)
NanoString Technol Inc, Seattle, WA USA.
Sullivan, Amy (författare)
NanoString Technol Inc, Seattle, WA USA.
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Lauttia, Susanna (författare)
Univ Helsinki, Biomed Helsinki, Lab Mol Oncol, Helsinki, Finland.
Lindman, Henrik (författare)
Uppsala universitet,Experimentell och klinisk onkologi
Nielsen, Torsten O. (författare)
Univ British Columbia, Genet Pathol Evaluat Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada.
Joensuu, Heikki (författare)
Univ Helsinki, Biomed Helsinki, Lab Mol Oncol, Helsinki, Finland.;Univ Helsinki, Comprehens Canc Ctr, Helsinki Univ Hosp, Helsinki, Finland.;Univ Helsinki, Dept Oncol, Helsinki, Finland.
Thompson, E. Aubrey (författare)
Mayo Clin, Ctr Comprehens Canc, Dept Canc Biol, Jacksonville, FL 32224 USA.
Chumsri, Saranya (författare)
Mayo Clin, Robert & Monica Jacoby Ctr Breast Hlth, Jacksonville, FL 32224 USA.
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Univ British Columbia, Genet Pathol Evaluat Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada;Univ British Columbia, Interdisciplinary Oncol Program, Fac Med, Vancouver, BC, Canada. NanoString Technol Inc, Seattle, WA USA. (creator_code:org_t)
2020
2020
Engelska.
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 26:11, s. 2603-2614
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Purpose: Recent studies have demonstrated a benefit of adjuvant capecitabine in early breast cancer, particularly in patients with triple-negative breast cancer (TNBC). However, TNBC is heterogeneous and more precise predictive biomarkers are needed. Experimental Design: Tumor tissues collected from TNBC patients in the FinXX trial, randomized to adjuvant anthracycline-taxane-based chemotherapy with or without capecitabine, were analyzed using a 770-gene panel targeting multiple biological mechanisms and additional 30-custom genes related to capecitabine metabolism. Hypothesis-generating exploratory analyses were performed to assess biomarker expression in relation to treatment effect using the Cox regression model and interaction tests adjusted for multiplicity. Results: One hundred eleven TNBC samples were evaluable (57 without capecitabine and 54 with capecitabine). The median follow-up was 10.2 years. Multivariate analysis showed significant improvement in recurrence-free survival (RFS) favoring capecitabine in four biologically important genes and metagenes, including cytotoxic cells [hazard ratio (HR) = 0.38; 95% confidence intervals (CI), 0.16-0.86, P-interaction = 0.01], endothelial (HR = 0.67; 95% CI, 0.20-2.22, P-interaction = 0.02), mast cells (HR = 0.78; 95% CI, 0.49-1.27, P-interaction = 0.04), and PDL2 (HR = 0.31; 95% CI, 0.12- 0.81, P- interaction = 0.03). Furthermore, we identified 38 single genes that were significantly associated with capecitabine benefit, and these were dominated by immune response pathway and enzymes involved in activating capecitabine to fluorouracil, including TYMP. However, these results were not significant when adjusted for multiple testing. Conclusions: Genes and metagenes related to antitumor immunity, immune response, and capecitabine activation could identify TNBC patients who are more likely to benefit from adjuvant capecitabine. Given the reduced power to observe significant findings when correcting for multiplicity, our findings provide the basis for future hypothesis- testing validation studies on larger clinical trials.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

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