Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy

A. M. Gonzalez-Angulo, S. Liu, H. Chen, M. Chavez-MacGregor, A. Sahin, G. N. Hortobagyi, G. B. Mills, K. A. Do, F. Meric-Bernstam

    Research output: Contribution to journalArticle

    13 Scopus citations

    Abstract

    Background: The purpose of this study was to determine the functional proteomic characteristics of residual breast cancer and hormone receptor (HR)-positive breast cancer after neoadjuvant systemic chemotherapy, and their relationship with patient outcomes. Methods: Reverse phase protein arrays of 76 proteins were carried out. A boosting approach in conjunction with a Cox proportional hazard model defined relapse predictors. A risk score (RS) was calculated with the sum of the coefficients from the final model. Survival outcomes and associations of the RS with relapse were estimated. An independent test set was used to validate the results. Results: Test (n = 99) and validation sets (n = 79) were comparable. CoxBoost revealed a three-biomarker (CHK1pS345, Caveolin1, and RAB25) and a two-biomarker (CD31 and Cyclin E1) model that correlated with recurrence-free survival (RFS) in all residual breast cancers and in HR-positive disease, respectively. Unsupervised clustering split patients into high- and low risk of relapse groups with different 3-year RFS (P ≤ 0.001 both). RS was a substantial predictor of RFS (P = 0.0008 and 0.0083) after adjustment for other substantial characteristics. Similar results were found in validation sets. Conclusions: We found models that independently predicted RFS in all residual breast cancer and in residual HRpositive disease that may represent potential targets of therapy in this resistant disease.

    Original languageEnglish (US)
    Article numbermds530
    Pages (from-to)909-916
    Number of pages8
    JournalAnnals of Oncology
    Volume24
    Issue number4
    DOIs
    StatePublished - Apr 2013

    Keywords

    • Breast cancer
    • Neoadjuvant chemotherapy
    • Residual disease

    ASJC Scopus subject areas

    • Hematology
    • Oncology

    Fingerprint Dive into the research topics of 'Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy'. Together they form a unique fingerprint.

  • Cite this

    Gonzalez-Angulo, A. M., Liu, S., Chen, H., Chavez-MacGregor, M., Sahin, A., Hortobagyi, G. N., Mills, G. B., Do, K. A., & Meric-Bernstam, F. (2013). Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy. Annals of Oncology, 24(4), 909-916. [mds530]. https://doi.org/10.1093/annonc/mds530