A relative ordering-based predictor for tamoxifen-treated estrogen receptor-positive breast cancer patients: multi-laboratory cohort validation.
Breast Cancer Res Treat
; 142(3): 505-14, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24253811
ABSTRACT
Current predictors for estrogen receptor-positive (ER-positive) breast cancer patients receiving tamoxifen are often invalid in inter-laboratory validation. We aim to develop a robust predictor based on the relative ordering of expression measurement (ROE) in gene pairs. Using a large integrated dataset of 420 normal controls and 1,129 ER-positive breast tumor samples, we identified the gene pairs with stable ROEs in normal control and significantly reversed ROEs in ER-positive tumor. Using these gene pairs, we characterized each sample of a cohort of 292 ER-positive patients who received tamoxifen monotherapy for 5 years and then identified relapse risk-associated gene pairs. We extracted a gene pair subset that resulted in the largest positive and negative predictive values for predicting 10-year relapse-free survival (RFS) using a genetic algorithm. A predictor was developed based on the gene pair subset and was validated in 2 large multi-laboratory cohorts (N = 250 and 248, respectively) of ER-positive patients who received 5-year tamoxifen alone. In the first validation cohort, the patients predicted to be tamoxifen sensitive had a 10-year RFS of 91 % (95 % confidence interval [CI] 85-97 %) with an absolute risk reduction of 34 % (95 % CI 17-51 %). The patients predicted to be tamoxifen insensitive had a significantly higher relapse risk than the patients predicted to be tamoxifen sensitive (hazard ratio = 4.99, 95 % CI 2.45-10.17, P = 9.13 × 10(-7)). Similar performance was achieved for the second validation cohort. The predictor performed well in both node-negative and node-positive subsets and added significant predictive power to the clinical parameters. In contrast, 2 previously proposed predictors did not achieve significantly better performances than the baselines of the validation cohorts. In summary, the proposed predictor can accurately and robustly predict tamoxifen sensitivity of ER-positive breast cancer patients and identified patients with a high probability of 10-year RFS following tamoxifen monotherapy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tamoxifeno
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Neoplasias de la Mama
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Receptores de Estrógenos
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Antineoplásicos Hormonales
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Breast Cancer Res Treat
Año:
2013
Tipo del documento:
Article
País de afiliación:
China