@article{3087254,
    title = "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",
    author = "Willis, S. and Polydoropoulou, V. and Sun, Y. and Young, B. and Tsourti, Z. and Karlis, D. and Long, B. and Lin, X. and Theel, S. and Carlson, J. and Györffy, B. and Williams, C. and Abramovitz, M. and Dafni, U. and Dowsett, M. and Leyland-Jones, B.",
    journal = "JCO Precision Oncology",
    year = "2018",
    number = "2",
    pages = "1-12",
    publisher = "American Society of Clinical Oncology",
    doi = "10.1200/PO.18.00016",
    keywords = "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",
    abstract = "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."
}