[18F]-Fluoroestradiol (FES) brain PET in the evaluation of patients with estrogen receptor positive breast cancer and known or suspected brain metastases.

Objective: Our purpose was to describe our initial institutional experience using dedicated brain [18F]-Fluoroestradiol (FES) PET/CT or PET/MRI in the management of patients with estrogen-receptor-positive (ER+) breast cancer brain metastases (BCBM), and compare to [18F]-Fluorodeoxyglucose (FDG) PET and MRI.

Materials & Methods: Patients with biopsy-proven ER+ disease and MRI findings of suspected new, progressive, or recurrent BCBM were included in this retrospective study. Clinical and demographic data were collected.

Facts and Perspectives: Implications of tumor glycolysis on immunotherapy response in triple negative breast cancer.

Triple negative breast cancer (TNBC) is an aggressive disease that is difficult to treat and portends a poor prognosis in many patients. Recent efforts to implement immune checkpoint inhibitors into the treatment landscape of TNBC have led to improved outcomes in a subset of patients both in the early stage and metastatic settings. However, a large portion of patients with TNBC remain resistant to immune checkpoint inhibitors and have limited treatment options beyond cytotoxic chemotherapy.

Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer.

Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy.

Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer.

Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls.

Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer.

Purpose: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

Endocrine Therapy-related Endocrinopathies-Biology, Prevalence and Implications for the Management of Breast Cancer.

Nearly 270,000 new breast cancer cases are predicted to be diagnosed in the USA in 2019 with more than 70% being estrogen receptor positive and treated using endocrine therapy. The suppression of estrogen biosynthesis or action via the use of ovarian suppression, aromatase inhibitors and selective estrogen receptor modulators/degraders, respectively, is effective in approximately 70% of women. The systemic inhibition of estrogen during breast cancer treatment is also associated with side effects due to the important endocrine functions of this steroid hormone, including its role in the maintenance of energy homeostasis and bone health.

Eribulin Plus Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase Ib/II Study.

Purpose: As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings.

Patients And Methods: In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting.

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531.

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531.

Akt Inhibition Is Associated With Favorable Immune Profile Changes Within the Tumor Microenvironment of Hormone Receptor Positive, HER2 Negative Breast Cancer.

The PI3K/Akt/mTOR pathway in part impacts tumorigenesis through modulation of host immune activity. To assess the effects of Akt inhibition on the tumor micro-environment (TME), we analyzed tumor tissue from patients with operable hormone receptor positive, HER2 negative breast cancer (BC) treated on a presurgical trial with the Akt inhibitor MK-2206. Quantitative multiplex immunofluorescence (qmIF) was performed using CD3, CD8, CD4, FOXP3, CD68, and pancytokeratin on biopsy and surgical specimens of MK-2206 and untreated, control patients.

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA-mutated metastatic breast cancer.

Inhibition of EZH2 Catalytic Activity Selectively Targets a Metastatic Subpopulation in Triple-Negative Breast Cancer.

Epigenetic changes are increasingly being appreciated as key events in breast cancer progression. However, breast cancer subtype-specific epigenetic regulation remains poorly investigated. Here we report that EZH2 is a leading candidate of epigenetic modulators associated with the TNBC subtype and that it predicts poor overall survival in TNBC patients.

Integrative Molecular Analysis of Patients With Advanced and Metastatic Cancer.

Purpose: We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis.

Patients And Methods: Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated.

SET: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer.

There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SET index to measure gene expression microarray probe sets that were correlated with hormone receptors ( and ) and robust to preanalytical and analytical influences. We tested SET index in biopsies of metastastic HR+/HER2- breast cancer against the treatment outcomes in 140 patients.

Phase I Trial of Veliparib, a Poly ADP Ribose Polymerase Inhibitor, Plus Metronomic Cyclophosphamide in Metastatic HER2-negative Breast Cancer.

Background: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy.

Methods: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer.

Randomized phase II trial of fulvestrant alone or in combination with bortezomib in hormone receptor-positive metastatic breast cancer resistant to aromatase inhibitors: a New York Cancer Consortium trial.

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A-500 mg intramuscular (i.

Residual Pure Intralymphatic Breast Carcinoma Following Neoadjuvant Chemotherapy Is Indicative of Poor Clinical Outcome, Even in Node-Negative Patients.

Residual carcinoma confined to lymphovascular spaces following neoadjuvant chemotherapy (NAC) for invasive breast carcinoma is an uncommon finding. We studied pathologic features and outcome for patients with pure intralymphatic carcinoma (PIC) following NAC, a pattern of residual disease reported to have a poor outcome in the only previously published series of this entity. Six of 284 (2.

Therapeutic Advances and New Directions for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely and and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP).

Therapies for triple negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is a heterogeneous disease associated with a high risk of recurrence, and therapeutic options are currently limited to cytotoxic therapy. Germ-line mutations may occur in up to 20% of unselected patients with TNBC, which may serve as a biomarker identifying which patients may have tumors that are particularly sensitive to platinums and/or inhibitors of poly(ADP-ribose)polymerase. A substantial proportion of patients with TNBCs not associated with germ-line BRCA mutations may have tumors that are ‘BRCA-like’, rendering those individuals potential candidates for similar strategies.

Circulating tumor cells in newly diagnosed inflammatory breast cancer.

Introduction: Circulating tumor cells (CTCs) are an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer. Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. The prognostic value of a CTC count in newly diagnosed IBC has not been established.