Τίτλος:
Exploratory analysis of single-gene predictive biomarkers in HERA DASL cohort reveals that C8A mRNA expression is prognostic of outcome and predictive of benefit of trastuzumab
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2-positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs. Methods To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted. Disease-free survival (DFS) was used as the end point in a Cox regression model, with the interaction term between C8A mRNA and treatment as a categorical variable split on the cohort mean. Results A significant interaction between C8A mRNA and treatment was detected (P < .001), indicating a predictive response to trastuzumab treatment. For the C8A-low subgroup (mRNA expression lower than the cohort mean), no significant treatment benefit was observed (P = .73). In the C8A-high subgroup, patients receiving trastuzumab experienced a lower hazard of a DFS event by approximately 75% compared with those in the observation arm (hazard ratio [HR], 0.25; P < .001). A significant prognostic effect of C8A mRNA also was seen (P < .001) in the observation arm, where the C8A-high group hazard of a DFS event was three times the respective hazard of the C8A-low group (HR, 3.27; P < .001). C8A mRNA is highly prognostic in the Hungarian Academy of Science HER2+ gastric cancer cohort (HR, 1.72; P < .001). Conclusion C8A as a single-gene biomarker prognostic of DFS and predictive of a benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer if validated by additional studies. Understanding the advantage of overexpression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer. © 2019 American Society of Clinical Oncology.
Συγγραφείς:
Willis, S.
Polydoropoulou, V.
Sun, Y.
Young, B.
Tsourti, Z.
Karlis, D.
Long, B.
Lin, X.
Theel, S.
Carlson, J.
Györffy, B.
Williams, C.
Abramovitz, M.
Dafni, U.
Dowsett, M.
Leyland-Jones, B.
Περιοδικό:
JCO Precision Oncology
Εκδότης:
American Society of Clinical Oncology
Λέξεις-κλειδιά:
complement component C8a; messenger RNA; trastuzumab, Article; cancer prognosis; cancer survival; clinical outcome; cohort analysis; controlled study; disease free survival; gene expression; human; human epidermal growth factor receptor 2 positive breast cancer; major clinical study; phase 3 clinical trial (topic); priority journal; randomized controlled trial (topic); stomach cancer
