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Background: Classification into molecular subtypes may increasingly be important for the selection of therapy for patients with early-stage breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome [Sorlie et al. PNAS 2001; Esserman et al. BCRT 2011]. In our study, we analyzed the response to neo-adjuvant chemotherapy and long-term outcomes using the 70-gene profile (MammaPrint) together with an 80-gene molecular subtyping profile (BluePrint). Methods: This analysis was performed on data from 421 patients: 141 patients from the I- SPY I trial; 230 patients from the biomarker discovery program at MD Anderson (131 and 99 respectively; Hess et al. JCO 2006; Iwamoto et al. BCRT 2011]; and 50 patients from the City of Hope [Somlo et al. ASCO 2010]. All patients were treated in the neo-adjuvant setting with chemotherapy. MammaPrint and BluePrint outcomes were determined from either 44K Agilent arrays run at Agendia or available through the I-SPY I data portal, or from Affymetrix U133A arrays. The combination of MammaPrint and BluePrint resulted in four distinct molecular groups: Luminal A (MammaPrint Low Risk/Luminal-type), Luminal B (MammaPrint High Risk/ Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the defined BluePrint molecular subgroups. pCR was observed in 3% of the Luminal A and 12% of Luminal B, in 38% of the HER2-type and in 42% of the Basal-type samples. 42% of patients with clinical HER2-positive phenotype are classified as Luminal-type by BluePrint: eight patients as Luminal A and 34 patients as Luminal B. 5-year distant metastases-free survival (DMFS) of patients with HER2-type by BluePrint who achieve pCR is 87%, compared with 78% for clinical HER2+ patients with pCR. These data are in line with a recent retrospective analysis of a large cohort of patients, which showed that pCR rate is not a suitable surrogate for clinical HER2+/Hormone Receptor-positive patients and is not associated with outcome [von Minckwitz et al. JCO 2012]. BluePrint classifies more patients as Basal-type (n = 120) with higher pCR rate (42%), compared with clinical subtyping (triple negative, n=93) with a pCR rate of 31%. Despite including eight clinical HER2+ and 11 triple-negative patients, those with BluePrint Luminal A subtype (n = 88) have excellent 5-year DMFS of 94% and appear to have no benefit from chemotherapy (low pCR rate). Conclusions: Molecular subtyping using BluePrint with MammaPrint can help to improve outcomes of patients in the neo-adjuvant setting over clinical subtyping. We observed differences in pCR and DMFS following neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint; for example, patients with Luminal A breast cancer (assessed with MammaPrint and BluePrint) have a good baseline prognosis with excellent survival and may not benefit from chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved in patients (pts) with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. We are reporting a preliminary planned analysis (first 6 cycles of treatment) of a phase 2 study that evaluates efficacy and safety of eribulin as first-line therapy for HER2-negative MBC. Methods: Pts with measureable HER2-negative locally recurrent or MBC with at least 12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate at 1.4 mg/m² IV on days 1 and 8 of each 3-week cycle. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were evaluated every 6 weeks for the first 6 cycles and every 6-12 weeks thereafter per RECIST 1.1. Results: 54 of 56 enrolled pts had at least 1 post-baseline assessment. The median number of cycles delivered was 7 (range 1,21). Pt characteristics: median age, 56 yrs (range 31-85); ECOG of 0, 32 (57%); 29% had de novo stage IV; 38/56 (68%) had prior neo/adjuvant (45% had anthracycline and 45% taxane, the majority of which were given together). Seventy percent have visceral disease (45% liver, 38% lung); 41 (73%) have estrogen receptor-positive (ER) disease and 12 (21%) have triple negative (TN) (ER-/PR-/HER2-) disease. Objective response data are found in Table 1. The most common treatment-related AEs are reported in Table 2. Treatment-related serious AEs occurred in 5 (9%) pts, neutropenia (4%), and febrile neutropenia (5%). Five pts stopped study therapy due to adverse events. Fourteen pts remain on study treatment. Conclusions: The preliminary results of this first-line study suggest that eribulin has antitumor activity in ER+/HER2- and TN MBC with an acceptable safety profile. Further exploration of this treatment as part of neo/adjuvant therapy is warranted. [ABSTRACT FROM AUTHOR]

Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25-27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions - patients likely to respond would be served well by current neoadjuvant chemotherapy protocols, while those unlikely to respond may be better suited to innovative new strategies for drug discovery [von Minckwitz et al. JCO 2006]. Genomics assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potential to provide information on the likelihood of a patient with LABC responding to neo- adjuvant therapy [Glück et al. ASCO 2012]. Trial design: MINT I is a prospective study designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors, to predict responsiveness to neo-adjuvant chemotherapy in patients with LABC. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint estrogen receptor (ER), progesterone receptor (PR) and HER2 single gene readout, and the 56-gene TheraPrint Research Gene Panel will be analyzed on a fresh tumor specimen using the whole genome array. Patients will receive neo- adjuvant chemotherapy pre-specified in the protocol. Response will be measured centrally. pCR is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ. Eligibility: The study will include women ≥18 years with histologically-proven invasive breast cancer T2 (≥3.5cm)-T4, N0M0 or T2-T4N1M0, adequate bone marrow reserves and normal renal and hepatic function who signed an IRB approved informed consent. Objectives: The objectives of the study are to: 1. Determine the predictive power of MammaPrint and BluePrint for sensitivity to neo-adjuvant chemotherapy as measured by pCR. 2. Compare TargetPrint ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment. 3. Identify correlations between TheraPrint and response to neo-adjuvant chemotherapy. 4. Identify and/or validate predictive gene expression profiles of clinical response or resistance to neo-adjuvant chemotherapy. 5. Compare BluePrint with IHC-based subtype classification. Statistical methods: Standard statistical tests such as the Pearson Chi-square test will be used to characterize and evaluate the relationship between chemoresponsiveness and gene expression patterns. Accrual: A total of 226 eligible patients will be enrolled from multiple institutions. To date (June 06, 2012), 31 patients have been enrolled. Clinical trial registry number: NCT01501487. [ABSTRACT FROM AUTHOR]