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, Gordon Mills, K. A. Do, F. Meric-Bernstam

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 1 2013
Externally publishedYes

Fingerprint

Residual Neoplasm
Proteomics
Breast Neoplasms
Recurrence
Drug Therapy
Survival
Biomarkers
Hormones
Protein Array Analysis
Cyclins
Proportional Hazards Models
Cluster Analysis
Proteins

Keywords

  • Breast cancer
  • Neoadjuvant chemotherapy
  • Residual disease

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Gonzalez-Angulo, A. M., Liu, S., Chen, H., Chavez-MacGregor, M., Sahin, A., Hortobagyi, G. N., ... 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

Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy. / Gonzalez-Angulo, A. M.; Liu, S.; Chen, H.; Chavez-MacGregor, M.; Sahin, A.; Hortobagyi, G. N.; Mills, Gordon; Do, K. A.; Meric-Bernstam, F.

In: Annals of Oncology, Vol. 24, No. 4, mds530, 01.04.2013, p. 909-916.

Research output: Contribution to journalArticle

Gonzalez-Angulo, AM, Liu, S, Chen, H, Chavez-MacGregor, M, Sahin, A, Hortobagyi, GN, Mills, G, Do, KA & Meric-Bernstam, F 2013, 'Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy', Annals of Oncology, vol. 24, no. 4, mds530, pp. 909-916. https://doi.org/10.1093/annonc/mds530
Gonzalez-Angulo AM, Liu S, Chen H, Chavez-MacGregor M, Sahin A, Hortobagyi GN et al. Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy. Annals of Oncology. 2013 Apr 1;24(4):909-916. mds530. https://doi.org/10.1093/annonc/mds530
Gonzalez-Angulo, A. M. ; Liu, S. ; Chen, H. ; Chavez-MacGregor, M. ; Sahin, A. ; Hortobagyi, G. N. ; Mills, Gordon ; Do, K. A. ; Meric-Bernstam, F. / Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy. In: Annals of Oncology. 2013 ; Vol. 24, No. 4. pp. 909-916.
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