title: Equivalence of MammaPrint array types in clinical trials and diagnostics.
abstract: MammaPrint is an FDA-cleared microarray-based test that uses expression levels of the 70 MammaPrint genes to assess distant recurrence risk in early-stage breast cancer. The prospective RASTER study proved that MammaPrint Low Risk patients can safely forgo chemotherapy, which is further subject of the prospective randomized MINDACT trial. While MammaPrint diagnostic results are obtained from mini-arrays, clinical trials may be performed on whole-genome arrays. Here we demonstrate the equivalence and reproducibility of the MammaPrint test. MammaPrint indices were collected for breast cancer samples: (i) on both customized certified array types (n = 1,897 sample pairs), (ii) with matched fresh and FFPE tissues (n = 552 sample pairs), iii) for control samples replicated over a period of 10 years (n = 11,333), and iv) repeated measurements (n = 280). The array type indicated a near perfect Pearson correlation of 0.99 (95 % CI: 0.989-0.991). Paired fresh and FFPE samples showed an excellent Pearson correlation of 0.93 (95 % CI 0.92-0.94), in spite of the variability introduced by intratumoral tissue heterogeneity. Control samples showed high consistency over 10 year's time (overall reproducibility of 97.4 %). Precision and repeatability are overall 98.2 and 98.3 %, respectively. Results confirm that the combination of the near perfect correlation between array types, excellent equivalence between tissue types, and a very high stability, precision, and repeatability demonstrate that results from clinical trials (such as MINDACT and I-SPY 2) are equivalent to current MammaPrint FFPE and fresh diagnostics, and can be used interchangeably.
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Inès
authors.initials: I
authors.lastname: Beumer
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Witteveen
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Delahaye
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: Wehkamp
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Mireille
authors.initials: M
authors.lastname: Snel
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: Dreezen
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Arno
authors.initials: A
authors.lastname: Floore
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: Brink
authors.affiliation: Agendia Inc, 22 Morgan, Irvine, CA 92618, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Chan
authors.affiliation: Divisions of Molecular Pathology and Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Linn
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Bernards
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: van 't Veer
authors.affiliation: Agendia NV, Science Park 406, 1098 XH, Amsterdam, The Netherlands. annuska.glas@agendia.com.
authors.forename: Annuska
authors.initials: A
authors.lastname: Glas
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011446:Prospective Studies; D015203:Reproducibility of Results; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*; D014021:Tissue Preservation
keywords: Breast cancer; Clinical prognostic value; Diagnostic microarray test; I-SPY; MINDACT; MammaPrint