title: BIRC5 (survivin): a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy.
abstract: OBJECTIVE
  Neoadjuvant systemic therapy (NAC) is currently used in the treatment of stage II/III breast cancer. Pathological complete response as a surrogate endpoint for clinical outcomes is not completely validated for all subgroups of breast cancers. Therefore, there is a need for reliable predictive tests of the most effective treatment.
  
  
  METHODS
  We used a combination of predictive clinical, pathological, and gene expression-based markers of response to NAC in a prospective phase II multicentre randomized clinical trial in breast cancer patients, with a long follow-up (8 years). This study concerned the subpopulation of 188 patients with similar levels of pathological response rates to sequential epirubicin/cyclophosphamide and docetaxel to determine predictive marker of pCR and DFS. We used a set of 45 genes selected from high throughput analysis and a standardized RT-qPCR. We analyzed the predictive markers of pathological complete response (pCR) and DFS in the overall population and DFS the subpopulation of 159 patients with no pCR.
  
  
  RESULTS
  In the overall population, combining both clinical and genomic variables, large tumor size, low TFF1, and MYBL2 overexpression were significantly associated with pCR. T4 Stage, lymphovascular invasion, negative PR status, histological type, and high values of CCNB1 were associated with DFS. In the no pCR population, only lymphovascular invasion and high values of BIRC5 were associated with DFS.
  
  
  CONCLUSIONS
  We confirm the importance of ER-related and proliferation genes in the prediction of pCR in NAC-treated breast cancer patients. Furthermore, we identified BIRC5 (survivin) as a main pejorative prognostic factor in patients with breast cancers with no pCR. These results also open perspective for predictive markers of new targeted therapies.
authors: Department of Biostatistics, Institut Curie, Paris, France.
authors: A S
authors: AS
authors: Hamy
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, Paris, France.
authors: I
authors: I
authors: Bieche
authors: APHP Molecular Oncology Unit, Hôpital Saint Louis, Paris Diderot University, 1 Avenue Claude Vellefaux, 75010, Paris, France.
authors: J
authors: J
authors: Lehmann-Che
authors: Biology Department, Institut Gustave Roussy, Villejuif, France.
authors: V
authors: V
authors: Scott
authors: APHP Pathology Department, Hôpital Saint Louis, Paris Diderot University, Paris, France.
authors: Ph
authors: P
authors: Bertheau
authors: Pathology Department, Hôpital René-Huguenin, Institut Curie, Saint-Cloud, France.
authors: J M
authors: JM
authors: Guinebretière
authors: Pathology Department, Institut Gustave Roussy, Villejuif, France.
authors: M C
authors: MC
authors: Matthieu
authors: Pathology Department, Institut Curie, Paris, France.
authors: B
authors: B
authors: Sigal-Zafrani
authors: APHP, Centre for Therapeutic Innovation, Saint-Louis Hospital, Paris, France.
authors: O
authors: O
authors: Tembo
authors: APHP, Centre for Therapeutic Innovation, Saint-Louis Hospital, Paris, France.
authors: M
authors: M
authors: Marty
authors: Department of Biostatistics, Institut Curie, Paris, France.
authors: B
authors: B
authors: Asselain
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, Paris, France.
authors: F
authors: F
authors: Spyratos
authors: APHP Molecular Oncology Unit, Hôpital Saint Louis, Paris Diderot University, 1 Avenue Claude Vellefaux, 75010, Paris, France. patricia.de-cremoux@aphp.fr.
authors: P
authors: http://orcid.org/0000-0003-0061-8700
authors: P
authors: de Cremoux
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D000077022:Survivin; D043823:Taxoids / Q000627:therapeutic use; D015534:Trans-Activators / Q000235:genetics; D016896:Treatment Outcome; D000071163:Trefoil Factor-1
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; C064352:MYBL2 protein, human; D000077022:Survivin; C051838:TFF1 protein, human; D043823:Taxoids; D015534:Trans-Activators; D000071163:Trefoil Factor-1; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide
keywords: BIRC5; Breast cancer; Neoadjuvant chemotherapy; Predictive