Abstract

Abstract Background Classification into molecular subtypes may be important for the selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS 2001; Esserman, BCRT 2011). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups using MammaPrint and BluePrint. Methods The study includes women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemotherapy (CT) or neo-adjuvant endocrine therapy (ET), 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. pCR is defined as no invasive or noninvasive residual disease in the breast or axillary lymph nodes. Results 191 Patients (median age 53, range 22-82), T1-4 N0-3, had definitive surgery and the overall pCR rate was 18%. 31 (16%) patients are classified as Luminal A-type (BluePrint Luminal/MammaPrint Low Risk) of whom 24 received neo-adjuvant CT; 1 patient (4%) had a pCR. While 7 patients received neo-adjuvant ET and 5 (71%) had a PR. 64 (34%) Patients are classified as Luminal B-type (BluePrint Luminal/MammaPrint High Risk). All but 1 patient received neo-adjuvant CT and 2 (3%) had a pCR. 30 (16%) Patients are classified as BluePrint HER2-type and all received neo-adjuvant CT and trastuzumab (except for 3 patients who did not receive trastuzumab); 11 (37%) had a pCR. 66 (31%) Patients are classified as BluePrint Basal-type and received neo-adjuvant CT; 19 (29%) had a pCR. Comparison of IHC/FISH classification with molecular subtyping: 24/102 (24%) IHC/FISH ER+/Her2- patients are not classified as Luminal-type by BluePrint (4 Her2, 20 Basal). 22/48 (46%) IHC/FISH Her2+ patients are not Her2-type by BluePrint (4 Luminal A, 11 Luminal B, and 7 Basal). All IHC/FISH triple negative patients are BluePrint Basal-type. Conclusions Molecular subtyping using MammaPrint and BluePrint leads to a reclassification of 24% (46/191) of tumors. We observed differences in pCR to neo-adjuvant treatment in groups stratified by BluePrint and MammaPrint. Patients with Luminal A-type breast cancer have a high response to neo-adjuvant endocrine therapy (71% PR) and low pCR (4%) to neo-adjuvant CT. While patients with BluePrint HER2-type and Basal-type breast cancer have a high pCR rate to neo-adjuvant CT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-02.

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