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A Supervised Risk Predictor of Breast Cancer Based on Biological Subtypes

ABSTRACT: Purpose: The biological subtypes of breast cancer designated as Luminal A, Luminal B, HER2+/ER-, and Basal-like are clinically important for prognosis and planning treatment strategies. Recognizing that there is a continuum in both the spectrum of breast cancer disease and the risk of survival, we sought to develop a clinical test for the biological subtypes using a supervised risk classier.Methods: Microarray and real-time quantitative RT-PCR (qRT-PCR) data from 189 samples, procured as fresh-frozen and formalin-fixed, paraffin-embedded tissues, were used to statistically select prototypical samples and genes for the biological subtypes of breast cancer. Predictions for biological subtype and risk of recurrence were determined for different stages of disease, treatments, and across analytical platforms. Results: The biological subtype predictions on a large combined microarray test set showed prognostic significance across all patients (1244 subjects; p<0.0001), on node negative patients with no adjuvant systemic therapy (738 subjects; p<0.0001), and on patients treated with endocrine therapy (404 subjects; p=0.001). Analysis of a neoadjuvant chemotherapy study revealed a high pathologic complete response (pCR) rate in HER2+/ER- and Basal-like patients. The subtype and risk predications were also highly significant when using the qRT-PCR assay from archived FFPE breast cancers. Conclusion: Our risk predictor based on distance to biological subtype centroids provides a continuous risk score that applies to all stages of breast cancer given current therapies. The assay can be performed using archived breast tissues and a real-time qRT-PCR assay, thus facilitating application to retrospective cohorts and clinical samples. Keywords: reference x sample Comparison of reference samples against treatment

ORGANISM(S): Homo sapiens  

SUBMITTER: Charles Perou   Charles M Perou  Joel S Parker  Philip S Bernard 

PROVIDER: E-GEOD-10886 | ArrayExpress | 2010-06-24



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PURPOSE To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression-based "intrinsic" subtypes luminal A, luminal B, HER2-enriched, and basal-like. METHODS A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and  ...[more]

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