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A Gene Expression Signature that Can Predict the Recurrence of Tamoxifen-Treated Primary Breast Cancer
- Source :
- Clinical Cancer Research, Clinical Cancer Research, American Association for Cancer Research, 2008, 14 (6), pp.1744-52. ⟨10.1158/1078-0432.CCR-07-1833⟩, Clinical Cancer Research, 2008, 14 (6), pp.1744-52. ⟨10.1158/1078-0432.CCR-07-1833⟩
- Publication Year :
- 2008
- Publisher :
- HAL CCSD, 2008.
-
Abstract
- Purpose: The identification of a molecular signature predicting the relapse of tamoxifen-treated primary breast cancers should help the therapeutic management of estrogen receptor–positive cancers. Experimental Design: A series of 132 primary tumors from patients who received adjuvant tamoxifen were analyzed for expression profiles at the whole-genome level by 70-mer oligonucleotide microarrays. A supervised analysis was done to identify an expression signature. Results: We defined a 36-gene signature that correctly classified 78% of patients with relapse and 80% of relapse-free patients (79% accuracy). Using 23 independent tumors, we confirmed the accuracy of the signature (78%) whose relevance was further shown by using published microarray data from 60 tamoxifen-treated patients (63% accuracy). Univariate analysis using the validation set of 83 tumors showed that the 36-gene classifier is more efficient in predicting disease-free survival than the traditional histopathologic prognostic factors and is as effective as the Nottingham Prognostic Index or the “Adjuvant!” software. Multivariate analysis showed that the molecular signature is the only independent prognostic factor. A comparison with several already published signatures demonstrated that the 36-gene signature is among the best to classify tumors from both training and validation sets. Kaplan-Meier analyses emphasized its prognostic power both on the whole cohort of patients and on a subgroup with an intermediate risk of recurrence as defined by the St. Gallen criteria. Conclusion: This study identifies a molecular signature specifying a subgroup of patients who do not gain benefits from tamoxifen treatment. These patients may therefore be eligible for alternative endocrine therapies and/or chemotherapy.
- Subjects :
- Oncology
Cancer Research
Pathology
Multivariate analysis
0302 clinical medicine
Cluster Analysis
classifier
Oligonucleotide Array Sequence Analysis
Aged, 80 and over
0303 health sciences
Univariate analysis
tamoxifen
Middle Aged
Prognosis
3. Good health
Treatment Outcome
Receptors, Estrogen
Chemotherapy, Adjuvant
030220 oncology & carcinogenesis
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Nottingham Prognostic Index
Female
Breast disease
Receptors, Progesterone
medicine.drug
Adult
medicine.medical_specialty
Antineoplastic Agents, Hormonal
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Sensitivity and Specificity
Article
Disease-Free Survival
03 medical and health sciences
Breast cancer
breast cancer
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
medicine
gene expression profiling
Humans
030304 developmental biology
Aged
business.industry
Carcinoma
Cancer
medicine.disease
Gene expression profiling
Drug Resistance, Neoplasm
Neoplasm Recurrence, Local
business
Tamoxifen
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 10780432 and 15573265
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research, Clinical Cancer Research, American Association for Cancer Research, 2008, 14 (6), pp.1744-52. ⟨10.1158/1078-0432.CCR-07-1833⟩, Clinical Cancer Research, 2008, 14 (6), pp.1744-52. ⟨10.1158/1078-0432.CCR-07-1833⟩
- Accession number :
- edsair.doi.dedup.....980f945eafcdc88cb491df47082e37d4