TY - JOUR
T1 - A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer
AU - Hatzis, Christos
AU - Pusztai, Lajos
AU - Valero, Vicente
AU - Booser, Daniel J.
AU - Esserman, Laura
AU - Lluch, Ana
AU - Vidaurre, Tatiana
AU - Holmes, Frankie
AU - Souchon, Eduardo
AU - Wang, Hongkun
AU - Martin, Miguel
AU - Cotrina, José
AU - Gomez, Henry
AU - Hubbard, Rebekah
AU - Chacón, J. Ignacio
AU - Ferrer-Lozano, Jaime
AU - Dyer, Richard
AU - Buxton, Meredith
AU - Gong, Yun
AU - Wu, Yun
AU - Ibrahim, Nuhad
AU - Andreopoulou, Eleni
AU - Ueno, Naoto T.
AU - Hunt, Kelly
AU - Yang, Wei
AU - Nazario, Arlene
AU - DeMichele, Angela
AU - O'Shaughnessy, Joyce
AU - Hortobagyi, Gabriel N.
AU - Symmans, W. Fraser
PY - 2011/5/11
Y1 - 2011/5/11
N2 - Context: Prediction of high probability of survival from standard cancer 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, Setting, and Patients: Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu) - negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline - based regimens (then endocrine therapy if estrogen receptor [ER] - positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. Main Outcome Measures: Distant relapse - free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years). Results: Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy. Conclusion: A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.
AB - Context: Prediction of high probability of survival from standard cancer 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, Setting, and Patients: Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu) - negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline - based regimens (then endocrine therapy if estrogen receptor [ER] - positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. Main Outcome Measures: Distant relapse - free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years). Results: Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy. Conclusion: A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.
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U2 - 10.1001/jama.2011.593
DO - 10.1001/jama.2011.593
M3 - Article
C2 - 21558518
AN - SCOPUS:79955798310
SN - 0098-7484
VL - 305
SP - 1873
EP - 1881
JO - JAMA
JF - JAMA
IS - 18
ER -