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Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient’s management and therapy selection

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Abstract

Background

Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored.

Methods

Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen’s coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated.

Results

The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467–0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25–28.67, and HR = 5.02, 95 % CI 0.96–26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04–0.69, P = 0.014).

Conclusions

The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient’s management and therapy selection.

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Acknowledgments

This work was supported by the Instituto de Salud Carlos III (FEDER) research grants FIS07/00316, RTICC12/0036/0006 and RD12/0036/0076 and NCI Breast SPORE program (P50-CA58223-09A1), and the Breast Cancer Research Foundation. AR: is supported by Rio Hortega post-residency fellowship, Instituto de Salud Carlos III.

Conflict of interest

C.M.P is an equity stock holder of BioClassifier LLC, and has filed a patent on the PAM50 assay. The rest of the authors have declared no conflict of interest.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain

    A. Romero, J. Á. García-Sáenz, M. de la Hoya, E. Díaz-Rubio & T. Cladés

  2. Molecular Oncology Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos, C/Prof. Martín Lagos s/n, 28040, Madrid, Spain

    A. Romero, M. de la Hoya, E. Díaz-Rubio & T. Cladés

  3. Unidad de Patología Mamaria, Hospital Clínico San Carlos, Madrid, Spain

    A. Romero, J. Á. García-Sáenz, A. Pelayo, V. Furió, J. M. Román & T. Cladés

  4. Valld’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    A. Prat

  5. Statistics Department, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain

    N. del Prado

  6. Pathology Department, Hospital Clínico San Carlos, Madrid, Spain

    A. Pelayo & V. Furió

  7. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    C. M. Perou

  8. Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    M. Martín

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  1. A. Romero
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  2. A. Prat
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Correspondence to A. Romero.

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Romero, A., Prat, A., García-Sáenz, J.Á. et al. Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient’s management and therapy selection. Clin Transl Oncol 16, 386–394 (2014). https://doi.org/10.1007/s12094-013-1088-z

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  • DOI: https://doi.org/10.1007/s12094-013-1088-z

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