Abstract

ABSTRACT Aim: The aim of the NBRST study is to compare a multi-gene classifier to conventional IHC/FISH subtyping to predict chemosensitivity as defined by pathological complete response (pCR), or endocrine sensitivity as defined by partial response (PR). Methods: The study includes women with histologically proven breast cancer, who will receive neo-adjuvant chemotherapy (NCT) or neo-adjuvant endocrine therapy (NET). BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 426 patients had definitive surgery. 37/211 (18%) IHC/FISH HR + /HER2- patients were re-classified by Blueprint as Basal (35) or HER2 (2). 53/123 (43%) IHC/FISH HER2+ patients were re-classified as Luminal (36) or Basal (17). 4/92 (4%) IHC/FISH triple negative (TN) patients were re-classified as Luminal (2) or HER2 (2). NCT pCR rates were 2% in Luminal A and 7% Luminal B patients versus 10% pCR in IHC/FISH HR + /HER2- patients. The NCT pCR rate was 53% in BluePrint HER2 patients. This is significantly superior (p = 0.047) to the pCR rate in IHC/FISH HER2+ patients (38%). The pCR rate of 36/75 IHC/FISH HER2 + /HR+ patients re-classified as BPLuminal is 3%. NCT pCR for BluePrint Basal patients was 49/140 (35%), comparable to the 34/92 pCR rate (37%) in IHC/FISH TN patients. Conclusions: BluePrint/MammaPrint molecular subtyping reclassifies 22% (94/426) of tumors, reassigning more responsive patients to the HER2 and Basal categories while reassigning less responsive patients to the Luminal category. These findings suggest that compared with IHC/FISH, BluePrint/MammaPrint more accurately identifies patients likely to respond (or not respond) to neo-adjuvant chemotherapy. Disclosure: F. De Snoo: Employee of Agendia; L. Stork-Sloots: Employee of Agendia. All other authors have declared no conflicts of interest.

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