Chemosensitivity and endocrine sensitivity prediction by MammaPrint and BluePrint in the Neoadjuvant Breast Registry Symphony Trial (NBRST).

Abstract

29 Background: Classification into molecular subtypes is important for the selection of therapy for patients with breast cancer. Previous analyses demonstrated that breast cancer subtypes have distinct clinical outcome (Gluck, BCRT 2013). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathologic complete response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups. Methods: The study includes women aged 18 to 90 with histologically proven breast cancer, who are scheduled to start neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy (NET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. Results: Of 336 patients, T1-4 N0-3, had definitive surgery and the overall pCR rate was 24%. 32/167 (19%) IHC/FISH ERPR+/Her2- patients were reclassified by BluePrint (31 Basal). 43/95 (45%) IHC/FISH Her2+ patients were reclassified by BluePrint (25 Luminal and 18 Basal). 3/74 (3%) IHC/FISH triple-negative patients were not Basal by BluePrint. Of 45 (13%) patients classified as Luminal A 32 received NCT; one patient (3%) had a pCR; 13 patients received NET and 9 (70%) had a PR. Of 116 (35%) patients classified as Luminal B, 111 received NCT and seven (6%) had a pCR. The pCR rate (17/149 (11%)) in IHC/FISH ERPR+/HER2- patients was higher. Fifty-five (16%) are BluePrint HER2 and received NCT (51 plus trastuzumab); 27 (49%) had a pCR compared to 35/95 (37%) in IHC/FISH HER2+ patients. One-hundred twenty (36%) are BluePrint Basal and received NCT; 46 (38%) had a pCR, similar to the pCR percentage seen in the 74 patients designated triple-negative by IHC/FISH. Conclusions: Molecular subtyping using MammaPrint and BluePrint leads to a reclassification of 23% (78/336) of tumors. BluePrint reclassification resulted in better grouping of patients into expected response groups compared to local surrogate subtyping with immunostains.