Chemotherapy response and recurrence-free survival in Neoadjuvant breast cancer depends on biomarker profiles: Results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657) Journal Article
| Authors: | Esserman, L. J.; Berry, D. A.; Cheang, M. C. U.; Yau, C.; Perou, C. M.; Carey, L.; De Michele, A.; Gray, J. W.; Conway-Dorsey, K.; Lenburg, M. E.; Buxton, M. B.; Davis, S. E.; Van't Veer, L. J.; Hudis, C.; Chin, K.; Wolf, D.; Krontiras, H.; Montgomery, L.; Tripathy, D.; Lehman, C.; Liu, M. C.; Olopade, O. I.; Rugo, H. S.; Carpenter, J. T.; Livasy, C.; Dressler, L.; Chhieng, D.; Singh, B.; Mies, C.; Rabban, J.; Chen, Y. Y.; Giri, D.; Au, A.; Hylton, N. |
| Article Title: | Chemotherapy response and recurrence-free survival in Neoadjuvant breast cancer depends on biomarker profiles: Results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657) |
| Abstract: | Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ?3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group. © Springer Science+Business Media, LLC. 2011. |
| Keywords: | adult; cancer survival; controlled study; human tissue; protein expression; treatment outcome; aged; disease-free survival; middle aged; cancer surgery; gene mutation; major clinical study; overall survival; genetics; mortality; clinical trials as topic; adjuvant therapy; cancer adjuvant therapy; disease free survival; neoadjuvant therapy; cancer staging; recurrence risk; antineoplastic agent; ki 67 antigen; metabolism; neoplasm recurrence, local; breast cancer; gene expression profiling; tumor volume; antineoplastic combined chemotherapy protocols; proportional hazards models; epidermal growth factor receptor 2; tumor markers, biological; aromatase inhibitor; cohort analysis; tumor biopsy; breast neoplasms; protein p53; tumor marker; monoclonal antibody; cancer hormone therapy; wound healing; tumor suppressor gene; proportional hazards model; minimal residual disease; neoplasm, residual; microarray analysis; tumor recurrence; nucleotide sequence; breast tumor; drug response; tamoxifen; multivariate analysis; taxoids; kaplan meier method; neoadjuvant chemotherapy; taxane derivative; trastuzumab; anthracycline; hormone receptor; anthracyclines; steroid receptor; receptors, steroid; multicenter studies as topic; taxoid; recurrence free survival; pathological complete response; clinical trial (topic); pathologic complete response; kaplan-meier estimate; multicenter study (topic); controlled clinical trial (topic); cancer prognosis; antibodies, monoclonal, humanized; molecular biomarkers |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 132 |
| Issue: | 3 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2012-04-01 |
| Start Page: | 1049 |
| End Page: | 1062 |
| Language: | English |
| DOI: | 10.1007/s10549-011-1895-2 |
| PROVIDER: | scopus |
| PMCID: | PMC3332388 |
| PUBMED: | 22198468 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 9 January 2013" - "CODEN: BCTRD" - "Molecular Sequence Numbers: GENBANK: GSE22226;" - "Source: Scopus" |
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