A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer

Christos Hatzis, Lajos Pusztai, Vicente Valero, Daniel J. Booser, Laura Esserman, Ana Lluch, Tatiana Vidaurre, Frankie Holmes, Eduardo Souchon, Hongkun Wang, Miguel Martin, José Cotrina, Henry Gomez, Rebekah Hubbard, J. Ignacio Chacón, Jaime Ferrer-Lozano, Richard Dyer, Meredith Buxton, Yun Gong, Yun WuNuhad Ibrahim, Eleni Andreopoulou, Naoto T. Ueno, Kelly Hunt, Wei Yang, Arlene Nazario, Angela DeMichele, Joyce O'Shaughnessy, Gabriel N. Hortobagyi, W. Fraser Symmans

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1873-1881
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume305
Issue number18
DOIs
StatePublished - May 11 2011

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Anthracyclines
Breast Neoplasms
Drug Therapy
Survival
Numbers Needed To Treat
Estrogen Receptors
Recurrence
Therapeutics
taxane
Neoplasms
Multicenter Studies
Multivariate Analysis
Outcome Assessment (Health Care)
Prospective Studies
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)

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A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. / Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Wang, Hongkun; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O'Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser.

In: JAMA - Journal of the American Medical Association, Vol. 305, No. 18, 11.05.2011, p. 1873-1881.

Research output: Contribution to journalArticle

Hatzis, C, Pusztai, L, Valero, V, Booser, DJ, Esserman, L, Lluch, A, Vidaurre, T, Holmes, F, Souchon, E, Wang, H, Martin, M, Cotrina, J, Gomez, H, Hubbard, R, Chacón, JI, Ferrer-Lozano, J, Dyer, R, Buxton, M, Gong, Y, Wu, Y, Ibrahim, N, Andreopoulou, E, Ueno, NT, Hunt, K, Yang, W, Nazario, A, DeMichele, A, O'Shaughnessy, J, Hortobagyi, GN & Symmans, WF 2011, 'A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer', JAMA - Journal of the American Medical Association, vol. 305, no. 18, pp. 1873-1881. https://doi.org/10.1001/jama.2011.593
Hatzis, Christos ; Pusztai, Lajos ; Valero, Vicente ; Booser, Daniel J. ; Esserman, Laura ; Lluch, Ana ; Vidaurre, Tatiana ; Holmes, Frankie ; Souchon, Eduardo ; Wang, Hongkun ; Martin, Miguel ; Cotrina, José ; Gomez, Henry ; Hubbard, Rebekah ; Chacón, J. Ignacio ; Ferrer-Lozano, Jaime ; Dyer, Richard ; Buxton, Meredith ; Gong, Yun ; Wu, Yun ; Ibrahim, Nuhad ; Andreopoulou, Eleni ; Ueno, Naoto T. ; Hunt, Kelly ; Yang, Wei ; Nazario, Arlene ; DeMichele, Angela ; O'Shaughnessy, Joyce ; Hortobagyi, Gabriel N. ; Symmans, W. Fraser. / A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. In: JAMA - Journal of the American Medical Association. 2011 ; Vol. 305, No. 18. pp. 1873-1881.
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abstract = "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.",
author = "Christos Hatzis and Lajos Pusztai and Vicente Valero and Booser, {Daniel J.} and Laura Esserman and Ana Lluch and Tatiana Vidaurre and Frankie Holmes and Eduardo Souchon and Hongkun Wang and Miguel Martin and Jos{\'e} Cotrina and Henry Gomez and Rebekah Hubbard and Chac{\'o}n, {J. Ignacio} and Jaime Ferrer-Lozano and Richard Dyer and Meredith Buxton and Yun Gong and Yun Wu and Nuhad Ibrahim and Eleni Andreopoulou and Ueno, {Naoto T.} and Kelly Hunt and Wei Yang and Arlene Nazario and Angela DeMichele and Joyce O'Shaughnessy and Hortobagyi, {Gabriel N.} and Symmans, {W. Fraser}",
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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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