title: A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response.
abstract: Classification of breast cancer into molecular subtypes maybe important for the proper selection of therapy, as tumors with seemingly similar histopathological features can have strikingly different clinical outcomes. Herein, we report the development of a molecular subtyping profile (BluePrint), that enables rationalization in patient selection for either chemotherapy or endocrine therapy prescription. An 80-Gene Molecular Subtyping Profile (BluePrint) was developed using 200 breast cancer patient specimens and confirmed on four independent validation cohorts (n = 784). Additionally, the profile was tested as a predictor of chemotherapy response in 133 breast cancer patients, treated with T/FAC neoadjuvant chemotherapy. BluePrint classification of a patient cohort that was treated with neoadjuvant chemotherapy (n = 133) shows improved distribution of pathological Complete Response (pCR), among molecular subgroups compared with local pathology: 56% of the patients had a pCR in the Basal-type subgroup, 3% in the MammaPrint Low-risk, Luminal-type subgroup, 11% in the MammaPrint High-risk, Luminal-type subgroup, and 50% in the HER2-type subgroup. The group of genes identifying Luminal-type breast cancer is highly enriched for genes having an Estrogen Receptor binding site proximal to the promoter-region, suggesting that these genes are direct targets of the Estrogen Receptor. Implementation of this profile may improve the clinical management of breast cancer patients, by enabling the selection of patients who are most likely to benefit from either chemotherapy or from endocrine therapy.
authors.affiliation: Research and Development, Agendia BV, Amsterdam, The Netherlands.
authors.forename: Oscar
authors.initials: O
authors.lastname: Krijgsman
authors.forename: Paul
authors.initials: P
authors.lastname: Roepman
authors.forename: Wilbert
authors.initials: W
authors.lastname: Zwart
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
authors.forename: Sun
authors.initials: S
authors.lastname: Tian
authors.forename: Femke A
authors.initials: FA
authors.lastname: de Snoo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bender
authors.forename: Rene
authors.initials: R
authors.lastname: Bernards
authors.forename: Annuska M
authors.initials: AM
authors.lastname: Glas
mesh_terms: D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone