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)

Laura J. Esserman, Donald A. Berry, Maggie C.U. Cheang, Christina Yau, Charles M. Perou, Lisa Carey, Angela De Michele, Joe W. Gray, Kathleen Conway-Dorsey, Marc E. Lenburg, Meredith B. Buxton, Sarah E. Davis, Laura J. Van't Veer, Clifford Hudis, Koei Chin, Denise Wolf, Helen Krontiras, Leslie Montgomery, Debu Tripathy, Constance LehmanMinetta C. Liu, Olufunmilayo I. Olopade, Hope S. Rugo, John T. Carpenter, Chad Livasy, Lynn Dressler, David Chhieng, Baljit Singh, Carolyn Mies, Joseph Rabban, Yunni Yi Chen, Dilip Giri, Alfred Au, Nola Hylton

Research output: Contribution to journalArticle

203 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1049-1062
Number of pages14
JournalBreast Cancer Research and Treatment
Volume132
Issue number3
DOIs
StatePublished - Apr 1 2012

Keywords

  • Breast cancer
  • Molecular biomarkers
  • Neoadjuvant chemotherapy
  • Pathologic complete response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., ... Hylton, N. (2012). 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). Breast Cancer Research and Treatment, 132(3), 1049-1062. https://doi.org/10.1007/s10549-011-1895-2