GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER
By C. Hatzis, L. Pusztai, V. Valero, D. Booser, L. Esserman, A. Lluch, T. Vidaurre, F. Holmes, E. Souchon, Hongkun Wang and 20 more. Journal of the American Medical Association (JAMA), 2011
630 citations recorded by the source corpus.
CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other genomic predictors showed paradoxically worse survival if predicted to be responsive to chemotherapy. CONCLUSION A genomic predictor combining ER status, predicted chemo-resistance, predicted chemo-sensitivity, and predicted endocrine sensitivity accurately identified patients with survival benefit following taxane-anthracycline chemotherapy.
Subfields: Cancer Research, Genetics, Oncology
View Paper: https://www.semanticscholar.org/paper/882afba9521441445030c7f52edc91959aa6b956
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Citations in the corpus
- The residual‐based predictiveness curve: A visual tool to assess the performance of prediction models (2016, background): “The data set considered in this section was collected by Hatzis et al. (2011).”
- Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection (2016, methodology): “dataset (GSE25066) generated by MD Anderson Cancer Center (MDACC) [8] consisted of 508 breast cancer gene expression profiles from HER2-negative breast cancer patients enrolled in a neoadjuvant chemotherapy trials that received an anthracycline-based and taxane regimen, either in combination or sequ”
- Differential Response to Neoadjuvant Chemotherapy Among 7 Triple-Negative Breast Cancer Molecular Subtypes (2013, background): “Hatzis and collegues (11) identified intrinsic subtypes in their study; thus, for 92 of our patients, we had data on PAM50 subtypes (luminal A, luminal B, HER2-enriched, basal-like, and normal-like; ref.”