Abstract P2-11-23: MammaPrint and BluePrint in early breast cancer: Clinical implications of prognostic stratification and molecular subtyping
Authors: K Yao, M Turk, K Kaul, J Wesseling, L Stork-Sloots, F de Snoo, M Cristofanilli
Journal: Cancer Research (2013)

Abstract Background: 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 [Glück et al. BCRT 2013]. The aim of this study is to compare tumor subtyping between clinical immunohistochemistry (IHC)/fluorescent in-situ (FISH) hybridization and MammaPrint and BluePrint and to determine which method of subtyping most accurately predicts long term outcome. Methods: 325 frozen/FFPE tumor samples from patients with AJCC stage TI-III, N0-Ib breast cancers were obtained from two separate cancer centers (NorthShore and Fox Chase Cancer Center) in the United States from 1992-2010. Median follow-up was 10.2 years. All patients underwent surgical excision and adjuvant therapy according to NCCN guidelines. Clinical subtyping included IHC and FISH whereas MammaPrint and BluePrint included microarray analysis. Results: Median age at diagnosis was 55 years (range 28-89 years) and 138 (42%) were AJCC Stage I, 119 (37%) Stage IIA, and 68 (21%) Stage IIB. One hundred three (33%) patients received adjuvant endocrine therapy (ET) alone, 84 (27%) received adjuvant chemotherapy (CT) alone, 104 (33%) received both modalities and 25 (7%) did not receive adjuvant treatment. Clinical Hormone Receptor (HR) and HER2 status assessment revealed that 208 (64%) of all tumors examined were luminal-like (ER/PR positive, HER2 negative), 52 (16%) were classified as HER2 positive and 65 (20%) as triple negative. Molecular classification using BluePrint demonstrated discordance in the following clinical groups: 20 out of 208 (10%) originally classified as luminal-like were reclassified as HER2-type (35%, n = 7) and as Basal-type (65%, n = 13) by BluePrint; 26 out of 52 (50%) previously identified as HER2 positive were reclassified as Luminal A (19%, n = 5), Luminal B (50%, n = 13), and 8 (31%) as Basal-type by BluePrint; 14 out of 65 (22%) patients originally identified as triple negative were reclassified as Luminal A (14%, n = 2), 5 (36%) as Luminal B and 7 (50%) as Basal-type by BluePrint. Molecular classification with BluePrint and MammaPrint identifies 40% of patients as Luminal A-type with 99% distant metastases free survival (DMFS) at 5 years. DMFS at 5-years for Luminal B tumors and HER2-type tumors was similar between clinical subtyping and BluePrint/MammaPrint subtyping but for triple negative tumors was different. For tumors using clinical subtyping, the DMFS for triple negative tumors was 84% compared to 93% for BluePrint/MammaPrint subtyping. Discordant cases are being centrally re-assessed for ER, PR and HER2. Conclusions: Molecular subtyping with BluePrint and MammaPrint leads to a more accurate molecular classification with clinically significant prognostic stratification. The use of MammaPrint and BluePrint in the management of patients with primary breast cancer should be considered to select adjuvant therapy in this era of personalized medicine. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-23.