Comparison of Molecular Subtyping with BluePrint, MammaPrint, and TargetPrint to Local Clinical Subtyping in Breast Cancer Patients

• Published in: Annals of surgical oncology 2012-10, Vol.19 (10), p.3257-3263
• Main Authors: Nguyen, Bichlien, Cusumano, Pino G., Deck, Kenneth, Kerlin, Deborah, Garcia, Agustin A., Barone, Julie L., Rivera, Edgardo, Yao, Katharine, de Snoo, Femke A., van den Akker, Jeroen, Stork-Sloots, Lisette, Generali, Daniele
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast Neoplasms - classification; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Oncology; Female; Gene Expression Profiling; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Ki-67 Antigen - metabolism; Medicine; Medicine & Public Health; Microarray Analysis; Middle Aged; Neoplasm Grading; Oncology; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; RNA, Messenger - genetics; Surgery; Surgical Oncology; Survival Rate
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-012-2561-6

Purpose To compare breast cancer subtyping with the three centrally assessed microarray-based assays BluePrint, MammaPrint, and TargetPrint with locally assessed clinical subtyping using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Methods BluePrint, MammaPrint, and TargetPrint were all performed on fresh tumor samples. Microarray analysis was performed at Agendia Laboratories, blinded for clinical and pathological data. IHC/FISH assessments were performed according to local practice at each institution; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) assessments were performed on 132 samples, and Ki-67 on 79 samples. Results The concordance between BluePrint and IHC/FISH subtyping was 94 % for the Luminal-type, 95 % for the HER2-type, and 94 % for the Basal-type subgroups. The concordance of BluePrint with subtyping using mRNA single gene readout (TargetPrint) was 96 % for the Luminal-type, 97 % for the HER2-type, and 98 % for the Basal-type subgroups. The concordance for substratification into Luminal A and B using MammaPrint and Ki-67 was 68 %. The concordance between TargetPrint and IHC/FISH was 97 % for ER, 80 % for PR, and 95 % for HER2. Conclusions The implementation of multigene assays such as TargetPrint, BluePrint, and MammaPrint may improve the clinical management of breast cancer patients. High discordance between Luminal A and B substratification based on MammaPrint versus locally assessed Ki-67 or grade indicates that chemotherapy decisions should not be based on the basis of Ki-67 readout or tumor grade alone. TargetPrint serves as a second opinion for those local pathology settings where high-quality standardization is harder to maintain.