title: EndoPredict predicts for the response to neoadjuvant chemotherapy in ER-positive, HER2-negative breast cancer.
abstract: The EndoPredict (EP) signature is a prognostic 11-gene expression signature specifically developed in ER+/HER2- node-negative/positive breast cancer. It is associated with relapse-free survival in patients treated with adjuvant hormone therapy, suggesting that EP low-risk patients could be treated with adjuvant hormone therapy alone whereas high-risk patients would deserve addition of adjuvant chemotherapy. Thus, it is important to determine whether EP high-risk patients are or are not more sensitive to chemotherapy than low-risk patients. Here, we have assessed the EP predictive value for pathological complete response to neoadjuvant chemotherapy in ER+/HER2- breast cancer. We gathered gene expression and histoclinical data of 553 pre-treatment ER+/HER2- breast carcinomas treated with anthracycline-based neoadjuvant chemotherapy. We searched for correlation between the pathological complete response (pCR) and the EP score-based classification. The overall pCR rate was 12%. Fifty-one percent of samples were classified as low-risk according to the EP score and 49% as high-risk. EP classification was associated with a pCR rate of 7% in the low-risk group and 17% in the high-risk group (p < 0.001). In multivariate analysis, the EP score remained significantly associated with pCR. Many genes upregulated in the high-risk tumours were involved in cell proliferation, whereas many genes upregulated in the low-risk tumours were involved in ER-signalling and stroma. Despite higher chemosensitivity, the high-risk group was associated with worse disease-free survival. In conclusion, EP high-risk ER+/HER2- breast cancers are more likely to respond to anthracycline-based chemotherapy.
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes (IPC), UMR1068 Inserm, 13009 Marseille, France; Faculté de Médecine, Aix-Marseille Université, 13001 Marseille, France. Electronic address: bertuccif@ipc.unicancer.fr.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes (IPC), UMR1068 Inserm, 13009 Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Faculté de Médecine, Aix-Marseille Université, 13001 Marseille, France; Département d'Oncologie Médicale, CRCM, IPC; UMR1068 Inserm, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes (IPC), UMR1068 Inserm, 13009 Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Breast cancer; EndoPredict; Neoadjuvant; Response to chemotherapy