Chemosensitivity predicted by BluePrint 80-gene functional subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

Abstract

Purpose: The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response.

Methods: The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2, and Basal.

Results: A total of 426 patients had definitive surgery. Thirty-seven of 211 (18 %) IHC/FISH hormone receptor (HR)+/HER2- patients were reclassified by Blueprint as Basal (n = 35) or HER2 (n = 2). Fifty-three of 123 (43 %) IHC/FISH HER2+ patients were reclassified as Luminal (n = 36) or Basal (n = 17). Four of 92 (4 %) IHC/FISH triple-negative (TN) patients were reclassified as Luminal (n = 2) or HER2 (n = 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 of 75 IHC/FISH HER2+/HR+ patients reclassified as BPLuminal is 3 %. NCT pCR for BluePrint Basal patients was 49 of 140 (35 %), comparable to the 34 of 92 pCR rate (37 %) in IHC/FISH TN patients.

Conclusions: BluePrint 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 more accurately identifies patients likely to respond (or not respond) to NCT.

Fig. 1

a pCR rates and major subtype re-assignments for patients classified by BluePrint/MammaPrint molecular subtyping compared with IHC/FISH assessed subgroups. The analysis includes only patients treated with NCT (n = 403). The two major subtype reassignments were (A) conventional luminal (HR+/HER2−) patients, 35 of 188 (19 %) patients reclassified by BluePrint as Basal (arrow A) and (B) conventional HER2+ patients, 36 of 123 (29 %) reclassified by BluePrint as Luminal (arrow B). b pCR rates and major subtype reassignments for conventional HER2+/HR+ (“triple positive”) patients (95 % treated with NCT/trastuzumab). Thirty-six of 75 (48 %) of conventional HER2+/HR+ patients were reclassified by BluePrint as Luminal—with only 1 pCR (3 %) to NCT (arrow A). Thirty-three of 75 (44 %) of conventional HER2+/HR+ patients were classified by BluePrint as HER2, with a pCR rate to NCT of 45 % (arrow B). Six conventional HER2+/HR+ patients were reassigned to BPBasal (not shown)