A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer, May 11, 2011, Hatzis et al. 305 (18): 1873 — JAMA

Original Contribution
JAMA. 2011;305(18):1873-1881. doi: 10.1001/jama.2011.593 A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast CancerChristos Hatzis, PhD; Lajos Pusztai, MD, DPhil; Vicente Valero, MD; Daniel J. Booser, MD; Laura Esserman, MD, MBA; Ana Lluch, MD; Tatiana Vidaurre, MD; Frankie Holmes, MD; Eduardo Souchon, MD; Hongkun Wang, PhD; Miguel Martin, MD; José Cotrina, MD; Henry Gomez, MD; Rebekah Hubbard, BS; J. Ignacio Chacón, MD; Jaime Ferrer-Lozano, MD; Richard Dyer, MD; Meredith Buxton, MS; Yun Gong, MD; Yun Wu, MD, PhD; Nuhad Ibrahim, MD; Eleni Andreopoulou, MD; Naoto T. Ueno, MD, PhD; Kelly Hunt, MD; Wei Yang, MD; Arlene Nazario, MD; Angela DeMichele, MD; Joyce O’Shaughnessy, MD; Gabriel N. Hortobagyi, MD; W. Fraser Symmans, MD


[+] Author Affiliations

Author Affiliations: Nuvera Biosciences Inc, Woburn, Massachusetts (Dr Hatzis); University of Texas M. D. Anderson Cancer Center, Houston (Drs Pusztai, Valero, Booser, Gong, Wu, Ibrahim, Andreopoulou, Ueno, Hunt, Yang, Nazario, Hortobagyi, and Symmans and Ms Hubbard); I-SPY Clinical Trial Investigators for the Cancer and Leukemia Group B, University of California at San Francisco (Dr Esserman and Ms Buxton) and University of Pennsylvania (Dr DeMichelle); Grupo Español de Investigación en Cáncer de Mama (GEICAM), Madrid, Spain (Drs Martin, Lluch, Chacón, and Ferrer-Lozano); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (Drs Vidaurre, Cotrina, Gomez, and Dyer); US Oncology The Woodlands, Texas (Dr Holmes and O’Shaughnessy); University of Texas Health Sciences Center, Lyndon B. Johnson Hospital, Houston (Dr Souchon); and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (Dr Wang).

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.

KEYWORDS: ALGORITHMS, ANTHRACYCLINES, BREAST NEOPLASMS, DECISION SUPPORT TECHNIQUES, FORECASTING, GENOME, HUMAN, GENOMICS, PROBABILITY, PROGNOSIS, SURVIVAL, TAXANE.
A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer, May 11, 2011, Hatzis et al. 305 (18): 1873 — JAMA




GENÉTICA
Actualidad Ultimas noticias - JANOes -
Un test genético abre la puerta al pronóstico de la supervivencia en el cáncer de mama
JANO.es · 02 Junio 2011 11:09

.El hallazgo permitirá saber qué pacientes responderán al tratamiento y cuáles no, lo que evitará terapias ineficaces y los efectos secundarios que conllevan.

En la investigación han participado más de 300 mujeres con cáncer de mama HER2 negativo de Estados Unidos, Perú y España.

Un test genético desarrollado por el Centro Oncológico MD Anderson de Houston, y en el que también ha trabajado el Grupo Español de Investigación en Cáncer de Mama (GEICAM), permitirá saber qué pacientes responderán al tratamiento, lo que evitará terapias ineficaces y los efectos secundarios que conllevan. El hallazgo abre la puerta al cálculo de la supervivencia en las mujeres que han contraído el tumor.

En la investigación, publicada en el Journal of the American Medical Association, y en la que han participado más de 300 mujeres con cáncer de mama HER2 negativo de Estados Unidos, Perú y España, se ha analizado el grado de quimiorresistencia y quimiosensibilidad de las pacientes a una pauta de tratamiento con taxanos y antraciclinas.

Se sabe que las pacientes que muestran una respuesta patológica completa tras recibir quimioterapia previa a la cirugía (neoadyuvante) viven más tiempo sin recaer (supervivencia libre de enfermedad), independientemente del estadio inicial del tumor. Las mayores tasas de respuesta patológica completa, aproximadamente del 30%, se han obtenido con quimioterapias que contenían un taxano. Ahora, gracias al test genético, se sabrá qué pacientes se van a beneficiar o no del tratamiento.

Según Ana Lluch, médico del Hospital Clínico de Valencia y miembro de GEICAM, “el test supone un avance en la búsqueda del esquema más adecuado en pacientes con cáncer de mama HER2 negativas que vayan a recibir terapia previa a la cirugía”.


Centro Oncológico MD Anderson (Houston)
Cancer Treatment and Cancer Research - MD Anderson Cancer Center

GEICAM
GEICAM - Grupo Español de Investigación en Cáncer de Mama

Jama (2011); doi: 10.1001/jama.2011.593
A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer, May 11, 2011, Hatzis et al. 305 (18): 1873 — JAMA

Journal of the American Medical Association
JAMA, the Journal of the American Medical Association, a weekly peer-reviewed medical journal published by AMA — JAMA


Actualidad Ultimas noticias - JANOes - Un test genetico abre la puerta al pronostico de la supervivencia en el cancer de mama - JANO.es - ELSEVIER