Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine.

Breast cancer is the most common cancer among women in the world as well as in the United States. Molecular and histological differentiation have helped clinicians optimize treatments with various therapeutics, including hormonal therapy, chemotherapy, immunotherapy, and radiation therapy. Recently, immunotherapy has become the standard of care in locally advanced triple-negative breast cancer and an option across molecular subtypes for tumors with a high tumor mutation burden.

A novel network-based method identifies a cuproplasia-related pan-cancer gene signature to predict patient outcome.

Copper is a vital micronutrient involved in many biological processes and is an essential component of tumour cell growth and migration. Copper influences tumour growth through a process called cuproplasia, defined as abnormal copper-dependent cell-growth and proliferation. Copper-chelation therapy targeting this process has demonstrated efficacy in several clinical trials against cancer.

Integrative Co-Registration of Elemental Imaging and Histopathology for Enhanced Spatial Multimodal Analysis of Tissue Sections through TRACE.

Summary: Elemental imaging provides detailed profiling of metal bioaccumulation, offering more precision than bulk analysis by targeting specific tissue areas. However, accurately identifying comparable tissue regions from elemental maps is challenging, requiring the integration of hematoxylin and eosin (H&E) slides for effective comparison. Facilitating the streamlined co-registration of Whole Slide Images (WSI) and elemental maps, TRACE enhances the analysis of tissue regions and elemental abundance in various pathological conditions.

Cancer Epidemiology in the Northeastern United States (2013-2017).

Unlabelled: We tested the hypotheses that adult cancer incidence and mortality in the Northeast region and in Northern New England (NNE) were different than the rest of the United States, and described other related cancer metrics and risk factor prevalence. Using national, publicly available cancer registry data, we compared cancer incidence and mortality in the Northeast region with the United States and NNE with the United States overall and by race/ethnicity, using age-standardized cancer incidence and rate ratios (RR). Compared with the United States, age-adjusted cancer incidence in adults of all races combined was higher in the Northeast (RR, 1.

Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis.

Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial.

Connecting copper and cancer: from transition metal signalling to metalloplasia.

Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient.

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.

Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer ("METRIC"): a randomized multicenter study.

The METRIC study (NCT#0199733) explored a novel antibody-drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.

Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer.

Purpose: Rash develops in approximately 50% of patients receiving alpelisib for breast cancer, often requiring dose modifications. Here, we describe the clinicopathologic, laboratory, and management characteristics of alpelisib-related dermatologic adverse events (dAEs).

Methods: A single center-retrospective analysis was conducted.

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.

Health-related quality of life in patients receiving first-line eribulin mesylate with or without trastuzumab for locally recurrent or metastatic breast cancer.

Background: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor approved for second-line (European Union) or third-line (United States) treatment of metastatic breast cancer. Two phase 2 single trials, evaluating first-line eribulin as monotherapy (Study 206; NCT01268150) or in combination with trastuzumab (Study 208; NCT01269346) in locally recurrent or metastatic breast cancer, demonstrated objective response rates of 28.6 and 71.

Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis.

Purpose: Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing metastatic breast cancer (MBC) drug therapies.

Methods: We searched the literature to identify clinical trials testing MBC drug therapies. Key eligibility criteria included at least 90% of patients enrolled in the trial having MBC, therapeutic clinical trials, and Phase II-III studies.

Regular use of aspirin and other non-steroidal anti-inflammatory drugs and breast cancer risk for women at familial or genetic risk: a cohort study.

Background: The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers.

Methods: We analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history.

Copper Depletion as a Therapeutic Strategy in Cancer.

Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche. As a result, copper depletion has emerged as a novel therapeutic strategy in the treatment of metastatic cancer.

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.

Background: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.

Functional Peptide Nanofibers with Unique Tumor Targeting and Enzyme-Induced Local Retention Properties.

An effective tumoral delivery system should show minimal removal by the reticuloendothelial system (RES), promote tumor uptake and penetration, and minimize on-site clearance. This study reports the design and synthesis of advanced self-assembling peptide nanofiber precursor (NFP) analogues. The peptidic nature of NFP offers the design flexibility for on-demand customization with imaging agents and surface charges while maintaining a set size, allowing for real-time monitoring of kinetic and dynamic tumoral delivery by multimodal fluorescence/positron emission tomography/computed tomography (fluo/PET/CT) imaging, for formulation optimization.

Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy.

Purpose: This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance.

Patients And Methods: Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35).

Efficacy and Safety of Ixabepilone and Capecitabine in Patients With Advanced Triple-negative Breast Cancer: a Pooled Analysis From Two Large Phase III, Randomized Clinical Trials.

Introduction: The purpose of this study was to evaluate the safety and efficacy of ixabepilone plus capecitabine in patients with metastatic or locally advanced triple-negative breast cancer (TNBC).

Patients And Methods: We conducted a pooled analysis of patients with TNBC enrolled in 2 phase III trials (NCT00080301 and NCT00082433), pretreated or resistant to an anthracycline and a taxane. In each study, patients were randomized to receive ixabepilone 40 mg/m (3-hour intravenous infusion, day 1), plus oral capecitabine 1000 mg/m twice daily (days 1-14), or capecitabine alone 1250 mg/m twice daily (days 1-14), every 3 weeks.