MammaPrint guides treatment decisions in breast Cancer: results of the IMPACt trial.

Background: Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients.

Methods: IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017.

Changing Landscape of Clinical-Genomic Oncology Practice.

The current paper discusses the use of genomics in the context of the changing landscape of clinical practice and modern medicine. Medical practice has shifted considerably over the past few decades, from empirical to evidence-based to personalized medicine, and the transition from reliance on observation to measureable parameters. Scientific innovation is required to collect an ever-increasing number and variety of data points and sophisticated analyses capable of distilling vast datasets into meaningful information.

Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers.

Immunohistochemically ER-positive HER2-negative (ER+HER2-) breast cancers are classified clinically as Luminal-type. We showed previously that molecular subtyping using the 80-gene signature (80-GS) reclassified a subset of ER+HER2- tumors to molecular Basal-type. We report here that molecular reclassification is associated with expression of dominant-negative ER variants and evaluate response to neoadjuvant therapy and outcome in the prospective neoadjuvant NBRST study (NCT01479101).

Association of 70-Gene Signature Assay Findings With Physicians' Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay.

Importance: Among patients who undergo the 21-gene assay (21-GA), 39% to 67% receive an intermediate risk result and may receive ambiguous treatment guidance. The 70-gene signature assay (70-GS) may be associated with physicians' treatment decisions in this population with early breast cancer.

Objective: To determine whether 70-GS findings are associated with physicians' decisions about adjuvant treatment and confidence in their recommendations and to evaluate the dichotomous (high- vs low-risk) and continuous distribution of 70-GS indices among this group of patients with intermediate risk.

Genomic Impact of Neoadjuvant Therapy on Breast Cancer: Incomplete Response is Associated with Altered Diagnostic Gene Signatures.

Purpose: Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response.

Methods: The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT.

KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity.

Kinase suppressors of Ras 1 and 2 (KSR1 and KSR2) function as molecular scaffolds to potently regulate the MAP kinases ERK1/2 and affect multiple cell fates. Here we show that KSR2 interacts with and modulates the activity of AMPK. KSR2 regulates AMPK-dependent glucose uptake and fatty acid oxidation in mouse embryonic fibroblasts and glycolysis in a neuronal cell line.