title: Molecular subtyping improves diagnostic stratification of patients with primary breast cancer into prognostically defined risk groups.
abstract: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy. The aim of this study was to evaluate the prognostic value of molecular subtyping using MammaPrint and BluePrint in women with early-stage breast cancer (BC) treated at US institutions following National Comprehensive Cancer Network standard guidelines. Tumor samples were collected from stage 1-2B consecutively diagnosed BC patients (n = 373) who underwent lumpectomy or mastectomy with an axillary staging procedure between 1992 and 2010 at two institutes (NorthShore University HealthSystem and Fox Chase Cancer Center) in the United States of America, with a median follow-up time of 9.5 years. MammaPrint low-risk patients had a 10-year DMFS of 96 % (95 %CI 92.8-99.4), while MammaPrint high-risk patients had a 10-year DMFS of 87 % (95 %CI 81.9-92.1) with a hazard ratio of 3.62 (95 %CI 1.38-9.50) (p = 0.005). Uni- and multivariate analyses included age, tumor size, grade, ER, and Her2; in multivariate analysis, MammaPrint reached near-significance (HR 3.01; p 0.08). When comparing BluePrint molecular subtyping with clinical stratification, the prognosis (10-year DMFS) was significantly different in 10-year DMFS between the different molecular subtypes (p < 0.001). This retrospective study with 10-year follow-up data provides valuable insight into prognosis of patients with primary BC comparing clinical with molecular subtyping. The BluePrint molecular stratification assay identifies patients with significantly different outcomes compared with standard clinical molecular stratification.
authors.affiliation: NorthShore University HealthSystem, 2650 Ridge Ave. Suite 1155, Evanston, IL, 60201, USA. kyao@northshore.org.
authors.forename: Katharine
authors.initials: K
authors.lastname: Yao
authors.affiliation: NorthShore University HealthSystem, 2650 Ridge Ave. Suite 1155, Evanston, IL, 60201, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldschmidt
authors.affiliation: NorthShore University HealthSystem, 2650 Ridge Ave. Suite 1155, Evanston, IL, 60201, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Turk
authors.affiliation: Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Agendia NV, Amsterdam, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stork-Sloots
authors.affiliation: Agendia NV, Amsterdam, The Netherlands. fdesnoo@medex15.com.
authors.forename: Femke
authors.initials: F
authors.lastname: de Snoo
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.|Robert Lurie Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D058889:Molecular Typing; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Molecular assay; Molecular subtyping; Prognosis