Inflammatory Breast Cancer: Understanding the Patient Experience.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive, locally advanced cancer with a 5-year survival rate of approximately 40%. Although patients with IBC likely experience significant and variable symptom burden from diagnosis through survivorship, the description of the symptom burden in this population is limited. OBJECTIVES: The purpose of this study was to describe the experience of patients with IBC and define the content domain for a patient-reported outcome measure of IBC symptom burden. METHODS: Twenty patients with IBC described their experience in single qualitative interviews. Content analysis was used to define the symptom burden content domain. Relevance ratings by a panel of experts reduced the number of items for a preliminary patient-reported outcome symptom burden measure. RESULTS: The mean (SD) participant age was 52.8 (12.0) years; 50.0% had distant metastatic disease, and 85.0% were currently receiving treatment. Content analysis revealed 45 symptoms, with 20 symptoms reported by greater than or equal to 20% of participants. All participants described localized disease-related symptoms. Treatment-related symptoms varied among participants based on the modalities received. CONCLUSION: Patients with IBC experience symptom burden that is distinct from the symptom burden experienced by patients with non-IBC. IMPLICATIONS FOR PRACTICE: Differentiating the disease-related symptoms of IBC may assist clinicians in making timely and accurate diagnoses for IBC. A disease- and treatment-specific measure of the symptom burden of IBC should be incorporated in clinical practice to allow for regular assessment and evaluation of symptom burden and implementation of evidence-based interventions for symptom management.

ONC201 and an MEK Inhibitor Trametinib Synergistically Inhibit the Growth of Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is a heterogeneous group of estrogen, progesterone, and HER2-negative breast cancers with poor clinical outcomes. The imipridone ONC201 is a G-protein-coupled dopamine receptor D2 modulator and an allosteric agonist of the mitochondrial protease caseinolytic protease P(ClpP), which induces apoptosis. Here, we aimed to develop a novel ONC201-based combination therapy targeting TNBC. We performed a reverse-phase protein array analysis of ONC201-treated/-untreated and -sensitive/-resistant cell lines to identify potential predictive biomarkers. A principal component analysis using measured protein expression levels, the apoptosis score (AS), and heatmaps of all the measured protein and AS-related protein expression levels did not show a clear correlation between the expression levels of a specific protein and ONC201 efficacy. Three-dimensional RNA interference kinome-wide library screening revealed the MAPK and PI3K/Akt pathways as potential synergistic therapeutic partners. The combination with the MEK inhibitor trametinib successfully inhibited the growth of both ONC201-sensitive/-resistant TNBC cell lines. The baseline ClpP level correlated with the efficacy of single-agent ONC201. Single and combination therapy increased caspase 3/7 activity. The predictive biomarkers and a detailed mechanism of synergy beyond an induction of caspase activation should be tested for translation into future studies.