Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 527
© 2008 American Society of Clinical Oncology

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Abstract

Combined use of genomic prognostic and treatment response predictors in breast cancer

University of Texas M. D. Anderson Cancer Center, Houston, TX; Nuvera Biosciences Inc, Woburn, MA; Institut Jules Bordet, Brussels, Belgium; Institut Goustave Roussy, Villejuif, France; Netherlands Cancer Institute, Amsterdam, Netherlands Antilles

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Background: An advantage of gene expression profiling-based diagnostic tests is that several different predictors can be applied to the same data and prognostic, as well as endocrine- and chemotherapy-sensitivity predictions can be generated from a single specimen. We tested this concept on two cohorts of breast cancers including a total of 427 cases. Methods: Gene expression profiling results generated with Affymetrix U133A gene chips were available on 198 stage I-II, lymph node-negative patients who received no systemic adjuvant therapy and on 229 stage I-III, HER-2 normal breast cancers who all received preoperative paclitaxel/FAC chemotherapy. We applied the Genomic Grade prognostic index (GGI) and 2 separate predictive signatures including a 200-gene endocrine sensitivity index and a 207-gene clinical phenotype-specific chemotherapy response predictor to each case. MammaPrint prognostic prediction results were also available on the 198 cases. The predictive accuracies of each of these tests were reported previously. Results: Sixty-four (32%) of the 198 cases from the prognostic data set were assigned to good prognosis by MammaPrint, among these low risk patients, 8 (12%) were predicted to be highly chemotherapy sensitive and 20 (31%) to be highly endocrine sensitive. Among the high risk patients, 69 (51%) were predicted to be highly sensitive to chemo- and 8 (6%) highly sensitive to endocrine-therapy while 57 (42%) showed low sensitivity to both modalities. In the neoadjuvant data, 82 patients (36%) were low risk for recurrence by the GGI (MammaPrint results were not available) and 10 of these (12%) were predicted to achieve excellent pathologic response (pCR or RCB-I). Sixty-one (41%) of the high-risk patients were predicted to have pCR/RCB-I response and 54% of the poor prognosis group was predicted to be insensitive to both endocrine- and chemotherapy. Conclusions: Patients predicted to be at low risk for recurrence are mainly sensitive to endocrine therapy but about 12% may also be sensitive to chemotherapy; 40–50% of high-risk patients are predicted to be insensitive to existing therapies. Simultaneous prediction of risk of recurrence and sensitivity to endocrine- and chemotherapies is currently possible and may allow more personalized treatment decisions in the future.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Agendia, Nuvera Biosciences Inc Nuvera Biosciences, Pfizer Inc, Roche Pharmaceuticals Agendia, Nuvera Biosciences, Nuvera Biosciences Inc Bristol-Myers Squibb, Genentech

Abstract presentation from the 2008 ASCO Annual Meeting