title: A gene expression signature that can predict the recurrence of tamoxifen-treated primary breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: U868 Institut National de la Sante et de la Recherche Medicale, Tumoral Identity and Plasticity, Cancer Research Center of Montpellier, Université Montpellier 1, CRLC Val d'Aurelle-Paul Lamarque, France.
authors.forename: Maïa
authors.initials: M
authors.lastname: Chanrion
authors.forename: Vincent
authors.initials: V
authors.lastname: Negre
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salvetat
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Mac Grogan
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Franck
authors.initials: F
authors.lastname: Molina
authors.forename: Charles
authors.initials: C
authors.lastname: Theillet
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Darbon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D012680:Sensitivity and Specificity; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen