Anticancer Activity of Region B Capsaicin Analogs.

The heterocyclic vanilloid compound capsaicin is responsible for the spicy and pungent flavor of chili peppers. Several convergent studies have shown that capsaicin suppresses the growth of multiple human cancers. Apart from capsaicin, natural and synthetic capsaicin-like compounds display growth suppressive activity in human cancers. The pharmacophore of capsaicin is comprised of three regions, namely region A (the aromatic ring), region B (the amide bond), and region C (the side chain). The present manuscript describes the isolation and synthesis of capsaicin analogs which have structural modifications in region B of the molecule. Furthermore, the pharmacokinetic properties, anticancer activity of region B capsaicin analogs, as well as the signaling pathways (underlying the growth-inhibitory effects of region B capsaicin analogs) have also been described. The discovery of novel, second-generation region B capsaicin analogs may foster the hope of innovative nutrition-based combination therapies in human cancers.

Role of mitochondrial translation in remodeling of energy metabolism in ER/PR(+) breast cancer.

Remodeling of mitochondrial energy metabolism is essential for the survival of tumor cells in limited nutrient availability and hypoxic conditions. Defects in oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis also cause a switch in energy metabolism from oxidative to aerobic glycolysis contributing to the tumor heterogeneity in cancer. Specifically, the aberrant expressions of mitochondrial translation components such as ribosomal proteins (MRPs) and translation factors have been increasingly associated with many different cancers including breast cancer. The mitochondrial translation is responsible for the synthesis 13 of mitochondrial-encoded OXPHOS subunits of complexes. In this study, we investigated the contribution of mitochondrial translation in the remodeling of oxidative energy metabolism through altered expression of OXPHOS subunits in 26 ER/PR(+) breast tumors. We observed a significant correlation between the changes in the expression of mitochondrial translation-related proteins and OXPHOS subunits in the majority of the ER/PR(+) breast tumors and breast cancer cell lines. The reduced expression of OXPHOS and mitochondrial translation components also correlated well with the changes in epithelial-mesenchymal transition (EMT) markers, E-cadherin (CHD1), and vimentin (VIM) in the ER/PR(+) tumor biopsies. Data mining analysis of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) breast cancer proteome further supported the correlation between the reduced OXPHOS subunit expression and increased EMT and metastatic marker expression in the majority of the ER/PR(+) tumors. Therefore, understanding the role of MRPs in the remodeling of energy metabolism will be essential in the characterization of heterogeneity at the molecular level and serve as diagnostic and prognostic markers in breast cancer.

Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.

Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.

Spherical Invasion Assay: A Novel Method to Measure Invasion of Cancer Cells.

The invasion of tumor cells into the neighboring blood vessels and lymph nodes is a vital step for distant metastasis. Traditionally, the invasive activity of growth factors (or the anti-invasive activity of drugs) is measured with the Boyden chamber assay. However, this assay has a few disadvantages like poor physiological relevance of transwell inserts and an inability to control chemokine gradients. The Boyden chamber assay is one of the most prevalent methods to measure the invasion of cancer cells. It would be advantageous to develop another assay that could validate the results of the Boyden chamber assay. With this in mind, our laboratory developed the spherical invasion assay (SIA) to measure the pro-invasive activity of human cancer cells. The SIA also circumvents some of the drawbacks of the Boyden chamber assay. The present manuscript measures the anti-invasive activity of the Src kinase inhibitor PP2 in A549 human non-small cell lung carcinoma (NSCLC) cells using the SIA. The SIA protocol is comprised of two steps. In the first step, A549 human NSCLC cells (treated or not with PP2) were mixed with Matrigel and seeded in the middle of an eight-well chamber slide. After 24 h, a second layer of Matrigel was overlaid over the first layer. Over the course of the next 24 h, the A549 cells invade from the primary to the secondary Matrigel layers. Subsequently, the cells are visualized by phase-contrast microscopy and the images obtained are quantified using ImageJ to calculate the anti-invasive activity of PP2 in A549 cells. The results of the SIA correlate well with Boyden chamber assays. The SIA may be adapted for multiple experimental designs, such as drug screening (to combat invasion and metastasis), measuring the pro-invasive activity of growth factors, and elucidating the signaling pathways underlying the pro-invasive/anti-invasive activity of biological modifiers. Graphic abstract: Diagrammatic illustration of the spherical invasion assay ( Hurley et al., 2017 ) . A. The first layer is comprised of human cancer cells mixed in a 1:1 suspension with Phenol Red containing Matrigel (represented as LAYER 1 in the figure). After 24 h, the cancer cells grow and extend up to the boundary of this first layer. B. A second layer of 1:1 solution Phenol Red-free Matrigel, in Phenol Red-free RPMI (represented as LAYER 2 in the figure) is added on top of the first Matrigel spot. The cells are incubated for 24 h at 37°C. C. Over these 24 h, the cancer cells invade from the primary layer into the secondary Matrigel layer. The chamber slides are observed by phase-contrast microscopy. D. A representative photograph of the images obtained by the SIA is shown. The black arrow indicates the cancer cells invading into the second layer of Matrigel. The dotted line represents the interface between the two layers. The distance to which the cells have traveled (into the secondary Matrigel layer) is measured at ten sites (for each photograph) in a randomized double-blind fashion by three independent observers, using NIH ImageJ Version 1.47. This process is repeated for three separate photographic fields per sample.

Anti-cancer activity of sustained release capsaicin formulations.

Capsaicin (trans-8-methyl-N-vanillyl-6-noneamide) is a hydrophobic, lipophilic vanilloid phytochemical abundantly found in chili peppers and pepper extracts. Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers. Despite its potent cancer-suppressing activity, the clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting. All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems. Most of the capsaicin-based the sustained release drugs have been tested for their pain-relieving activity. Only a few of these formulations have been investigated as anti-cancer agents. The present review describes the physicochemical properties, bioavailability, and anti-cancer activity of capsaicin-sustained release agents. The asset of such continuous release capsaicin formulations is that they display better solubility, stability, bioavailability, and growth-suppressive activity than the free drug. The encapsulation of capsaicin in sustained release carriers minimizes the adverse side effects of capsaicin. In summary, these capsaicin-based sustained release drug delivery systems have the potential to function as novel chemotherapies, unique diagnostic imaging probes and innovative chemosensitization agents in human cancers.

Effect of Tart Cherry on Aromatase Inhibitor-Induced Arthralgia (AIA) in Nonmetastatic Hormone-Positive Breast Cancer Patients: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: Aromatase Inhibitor induced Arthralgia (AIA) can cause noncompliance leading to decreased breast-cancer survival. Effective interventions for AIA are limited. Tart cherry (TC) showed beneficial effect on musculoskeletal pain. 48 patients (Pts) randomized to TC versus placebo over 6 weeks, TC (23pts) had 34.7% mean pain decrease versus 1.4% in Placebo (25pts). TC can improve AIA in nonmetastatic breast-cancer patients. METHODS: Randomized, placebo-controlled, double-blind trial. Eligible patients with NMHPBC on AI for at least 4 weeks were randomized to TC concentrate [50 tart cherries] vs. placebo (P) [syrup] in 1:1 model. Patients instructed to consume 1 Oz of concentrate in 8 Oz water daily for 6 weeks, and document their pain intensity at baseline, weekly and at study completion in a diary using Visual Analog Scale (VAS), with 0 mm indicating no pain, and 100 mm indicating highest pain. RESULTS: Sixty patients were enrolled. Two patients did not complete the study due to diarrhea, and 10 patients were noncompliant. Forty-eight patients were included in the final analysis. TC group (23 pts) had 34.7% mean decrease in pain compared to 1.4% in P group (25 pts). This difference was statistically significant (Mann-Whitney U Test, P = .034). CONCLUSIONS: Tart cherry can significantly improve AIA in nonmetastatic breast cancer patient.

Pneumonitis and cellular immunodeficiency triggered by the CDK 4/6 inhibitor Abemaciclib.

Breast cancer is the second most common cancer amongst women in the United States following non-melanoma skin cancer. There were an estimated 276,480 new cases and 42,170 deaths in 2020. The lifetime risk for developing breast cancer in females is about 13%. In the United States this year approximately 284,200 people out of which 281,550 women and 2,650 men, will be diagnosed with invasive breast cancer. In recent years, treatment options with novel mechanisms have emerged. Cyclin dependent kinase (CDK) 4/6 inhibitors, namely palbociclib, ribociclib and abemaciclib, are relatively new targeted therapies for treating breast cancers express estrogen receptors (ER) and/or progesterone receptors (PR). CDKs are important regulatory enzymes in cell cycle transitions and cell division. Selective inhibition of CDK4/6 causes cell cycle to arrest in the G1 phase, resulting in reduced cell viability and tumor response. Abemaciclib is the only one approved as monotherapy. Palbociclib and ribociclib must be used as adjunctive therapy to endocrine therapy such as tamoxifen, aromatase inhibitors or fulvestrant. Common side effects include neutropenia, thrombocytopenia, fatigue, nausea, and vomiting. A black box warning for all CDK inhibitors is a rare but possibly fatal severe inflammation of the lungs, called pneumonitis. We present a fatal case of severe pneumonitis with superimposed fungal respiratory infection in the setting of hypogammaglobulinemia in a 65-year-old female with metastatic ER and PR positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer who received abemaciclib.

Hormone Receptor Positive/HER2 Negative Breast Cancer With Isolated Bladder Metastasis: A Rare Case.

Breast cancer is the most common cancer diagnosed in women in North America. Hormone receptor positive (HR+) and HER2 negative (HER2-) breast cancers account for at least 60% to 70% of all breast cancer cases. They usually metastasize to lymph nodes, bones, liver, lungs, and brain. Urinary bladder is a very unusual site for metastatic HR+/HER2- breast cancer and occurs in only 2% of all metastatic disease. In this article, we present a case of a 63-year-old female with locally advanced breast cancer who underwent mastectomy, adjuvant chemotherapy, radiation, and hormonal therapy. She was in remission for almost 17 years and subsequently presented with hematuria and lower abdominal pain. Cystoscopy was performed, which showed evidence of bladder wall thickening. Histopathology showed metastatic HR+/HER2- breast cancer consistent with her history of breast primary. Imaging studies did not show any other evidence of metastatic disease. She was started on cyclin D kinase 4/6 inhibitor, palbociclib, in combination with an aromatase inhibitor, letrozole. This is an exceedingly rare case of HR+ and HER2- breast cancer with metastasis to the urinary bladder. The late onset of recurrence with bladder metastasis makes this case very unique and to our knowledge only few similar cases have been reported in the literature.

Detecting early onset of anthracyclines-induced cardiotoxicity using a novel panel of biomarkers in West-Virginian population with breast cancer.

Cardiotoxic manifestation associated with breast cancer treatment by anthracycline regimen increases patients' susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post-anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. This study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, further assessing their correlation with cardiac injury specific markers, troponin I and T, and demonstrate the development of cardiac dysfunction in breast cancer patients. Blood obtained from West Virginian females clinically diagnosed with breast cancer and receiving anthracyclines showed upregulated level of biomarkers and circulating miRNAs after 3 and 6 months of chemotherapy initiation with increased levels of cardiac troponin I and T. These biomarkers and miRNAs significantly correlated with elevated troponins. Following 6 months of anthracycline-regimens, 23% of the patient population showed cardiotoxicity with reduced left ventricular ejection fraction. Our results support the clinical application of plasma biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.

An updated review of epidemiology, risk factors, and management of male breast cancer.

Unlike female breast cancer, male breast cancer (MBC) is rare and not very well understood. Prospective data in the management of MBC are lacking and majority of treatment strategies are adopted from the established guidelines for breast cancer in women. The understanding of biology, clinical presentation, genetics, and management of MBC is evolving but there still remains a large knowledge gap due to the rarity of this disease. Older age, high estradiol levels, klinefelter syndrome, radiation exposure, gynecomastia, family history of breast cancer, BRCA2 and BRCA1 mutation are some of the known risk factors for MBC. Routine screening mammography is not recommended for asymptomatic men. Diagnostic mammogram with or without ultrasound should be considered if there is a suspicion for breast mass. Majority of men with early-stage breast cancer undergo mastectomy whereas breast conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) remains an alternative option in selected cases. Since the majority of MBC are hormone receptor positive (HR+), adjuvant hormonal therapy is required. Tamoxifen for a total of 5 to 10 years is the mainstay adjuvant hormonal therapy. The role of neoadjuvant and adjuvant chemotherapy for early-stage breast cancer is uncertain and not commonly used. The role of gene recurrence scores like oncotype Dx and mammaprint is evolving and can be used as an aid for adjuvant chemotherapy. Majority of metastatic MBC are treated with hormonal therapy with either tamoxifen, gonadotropin-releasing hormone agonist (GnRH) with aromatase inhibitors (AI), or fulvestrant. Chemotherapy is reserved for patients with visceral crisis or rapidly growing tumors.

Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy.

Capsaicin displays robust growth-inhibitory activity in multiple human cancers. However, the feasibility of capsaicin as a clinically relevant anticancer drug is hampered by its adverse side effects. This concern has led to extensive research focused on the isolation and synthesis of second-generation nonpungent capsaicin analogues with potent antineoplastic activity. A major class of nonpungent capsaicin-like compounds belongs to the N-acyl-vanillylamide (N-AVAM) derivatives of capsaicin (hereafter referred as N-AVAM capsaicin analogues). This perspective discusses the isolation of N-AVAM capsaicin analogues from natural sources as well as their synthesis by chemical and enzymatic methods. The perspective describes the pharmacokinetic properties and anticancer activity of N-AVAM capsaicin analogues. The signaling pathways underlying the growth-inhibitory effects of N-AVAM capsaicin analogues have also been highlighted. It is hoped that the insights obtained in this perspective will facilitate the synthesis of a second generation of N-AVAM capsaicin analogues with improved stability and growth-suppressive activity in human cancer.

Breast cancer in a patient with Birt-Hogg-Dubé syndrome (BHDS) with dramatic response to neoadjuvant chemotherapy.

This is a case of 49-year-old white woman who presented with a rapidly growing right sided breast mass. A subsequent punch biopsy confirmed grade 3 invasive mammary carcinoma of no special type which was negative for oestrogen receptor, progesterone receptor and Her-2 neu overexpression. She was a carrier of folliculin gene mutation that is characteristic of Birt-Hogg-Dubé syndrome (BHDS), a condition known to cause skin lesions, renal cancers and pneumothoraces. Family history revealed patient's mother, grandmother and maternal aunt developed renal cell carcinomas during their lifetime and were positive for the same germ line mutation. Tumour tissue was positive for TP53 mutation and negative for BRCA1, BRCA2 and other genes commonly associated with breast cancer. We report a patient with BHDS presenting with breast cancer that showed dramatic response to neoadjuvant chemotherapy prior to bilateral mastectomy, local chest wall radiation and 6 months of adjuvant capecitabine.

Capsaicinoids: Multiple effects on angiogenesis, invasion and metastasis in human cancers.

Cancer progression is a complex multistep process comprising of angiogenesis of the primary tumor, its invasion into the surrounding stroma and its migration to distant organs to produce metastases. Nutritional compounds of the "capsaicinoid" family regulate angiogenesis, invasion and metastasis of tumors. Capsaicinoids display robust anti-angiogenic activity in both cell culture and mice models. However, conflicting reports exist about the effect of capsaicinoids on invasion of metastasis of cancers. While some published reports have described an anti-invasive and anti-metastatic role for capsaicinoids, others have argued that capsaicinoids stimulate invasion and metastasis of cancers. The present review article summarizes these findings involving the bioactivity of capsaicin in angiogenesis, invasion and metastasis of cancer. A survey of literature indicate that they are several articles summarizing the growth-inhibitory activity of capsaicinoids but few describe its effects on angiogenesis, invasion and metastasis in detail. Our review article fills this gap of knowledge. The discovery of a second generation of natural and synthetic capsaicin analogs (with anti-tumor activity) will pave the way to improved strategies for the treatment of several human cancers.

Capsaicinoids enhance chemosensitivity to chemotherapeutic drugs.

Cytotoxic chemotherapy is the mainstay of cancer treatment. Conventional chemotherapeutic agents do not distinguish between normal and neoplastic cells. This leads to severe toxic side effects, which may necessitate the discontinuation of treatment in some patients. Recent research has identified key molecular events in the initiation and progression of cancer, promoting the design of targeted therapies to selectively kill tumor cells while sparing normal cells. Although, the side effects of such drugs are typically milder than conventional chemotherapies, some off-target effects still occur. Another serious challenge with all chemotherapies is the acquisition of chemoresistance upon prolonged exposure to the drug. Therefore, identifying supplementary agents that sensitize tumor cells to chemotherapy-induced apoptosis and help minimize drug resistance would be valuable for improving patient tolerance and response to chemotherapy. The use of effective supplementary agents provides a twofold advantage in combination with standard chemotherapy. First, by augmenting the activity of the chemotherapeutic drug it can lower the dose needed to kill tumor cells and decrease the incidence and severity of treatment-limiting side effects. Second, adjuvant therapies that lower the effective dose of chemotherapy may delay/prevent the development of chemoresistance in tumors. Capsaicinoids, a major class of phytochemical compounds isolated from chili peppers, have been shown to improve the efficacy of several anti-cancer drugs in cell culture and animal models. The present chapter summarizes the current knowledge about the chemosensitizing activity of capsaicinoids with conventional and targeted chemotherapeutic drugs, highlighting the potential use of capsaicinoids in novel combination therapies to improve the therapeutic indices of conventional and targeted chemotherapeutic drugs in human cancers.

Colonic Obstruction from an Unusual Cause: A Rare Case of Metastatic Invasive Ductal Carcinoma to the Colon.

Colon metastasis from breast cancer is rare. Gastrointestinal (GI) metastasis is more frequently seen in patients with invasive lobular carcinoma of the breast compared to invasive ductal carcinoma; however, the most common sites of metastasis still remain the lymph nodes, lungs, liver, and bones. We describe a 68-year-old female with a remote history of invasive ductal carcinoma of the breast who presented with abdominal pain and a palpable mass. On imaging, she was found to have a colonic obstruction and underwent a right hemicolectomy that proved to be metastatic invasive ductal carcinoma of the breast.

Factors Associated with Functional Decline in Elderly Female Breast Cancer Patients in Appalachia.

Background Functional status has been previously shown in the elderly cancer population to predict both mortality as well as treatment tolerance. The goal of this study was to determine if there are certain subsets of the elderly breast cancer population that are at higher risk of experiencing functional decline following treatment. Methods Patient charts from the Edwards Comprehensive Cancer Center in Huntington, West Virginia, from January 2006 - January 2016 were reviewed. Relevant inclusion criteria included patients of 65 years of age and older with a new diagnosis of Stage 0-III breast cancer. Functional decline was defined as an increase of at least one point in Eastern Cooperative Oncology Group (ECOG) scores within one year of diagnosis. ECOG performance status was subjectively determined by the physician. Fisher's exact test and Pearson's Chi-squared test were initially utilized to assess potential factors associated with functional decline such as pretreatment ECOG score, age at diagnosis, stage, hormone receptor status, type of surgery received, whether radiation therapy, chemotherapy, or hormonal therapy was received, medical comorbidities, body mass index (BMI), complaints of weakness at diagnosis, and ambulatory status. Factors that were found to be significant were further assessed via multivariate logistic regressions. Results Three-hundred and fourteen patients were identified as meeting inclusion criteria. At one-year follow-up, 45 patients (14.3% of the cohort) had documented functional decline. On initial analysis, factors associated with functional decline included Stage III disease (p=0.002) and complaints of weakness at diagnosis (p=0.004). Following multivariate analysis, Stage III disease (p = 0.02), complaints of weakness at diagnosis (p = 0.04), and bilateral mastectomy (p = 0.03) were significantly associated with functional decline. Conclusion Patients who were diagnosed with Stage III breast cancer, had complaints of weakness at time of diagnosis, or had bilateral mastectomies were more likely to have a decline in functional status at one-year follow-up. Awareness of factors associated with functional decline in the elderly Appalachian population with Stage 0-III breast cancer will be useful during discussions regarding patient expectations, treatment, and goals of care. Elderly breast cancer patients for whom bilateral prophylactic mastectomies are not indicated may be better served by lumpectomy alone (based on patient age, hormone receptor status, and tumor size), lumpectomy followed by radiation therapy, or unilateral mastectomy to maximize the likelihood of functional preservation following treatment.

Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination.

A 62-year-old white female with a history of early-stage triple-negative breast cancer on a combination of carboplatin and paclitaxel in the adjuvant setting presented with lower gastrointestinal bleeding. She tolerated 4 cycles of dose-dense adriamycin/cyclophosphamide with no major symptoms. After 6 cycles of weekly paclitaxel in combination with carboplatin every 3 weeks, she presented with diarrhea and lower gastrointestinal bleeding. Colonosopic examination showed erythema and inflammation in the splenic flexure, descending colon, and sigmoid colon consistent with ischemic colitis. Pathology favored the same diagnosis. She was treated conservatively with intravenous fluids and bowel rest. Chemotherapy was held for 2 weeks and resumed after recovery without carboplatin. She was able to tolerate the remaining 6 cycles of paclitaxel with no recurrence of her symptoms.

Creating a Biomarker Panel for Early Detection of Chemotherapy Related Cardiac Dysfunction in Breast Cancer Patients.

Cardiotoxicity is an important issue for breast cancer patients receiving anthracycline-trastuzumab therapy in the adjuvant setting. Studies show that 3-36% of patients receiving anthracyclines and/or trastuzumab experience chemotherapy related cardiac dysfunction (CRCD) and approximately 17% of patients must stop chemotherapy due to the consequences of CRCD. There is currently no standardized, clinically verified way to detect CRCD early, but common practices include serial echocardiography and troponin measurements, which can be timely, costly, and not always available in areas where health care resources are scarce. Furthermore, detection of CRCD, before there is any echocardiographic evidence of dysfunction or clinical symptoms present, would allow maximal benefit of chemotherapy and minimize cardiac complications. Creating a panel of serum biomarkers would allow for more specificity and sensitivity in the early detection of CRCD, which would be easy to implement and cost effective in places with limited health care. Based on a review of the literature, we propose creating a biomarker panel consisting of topoisomerase 2ß, serum troponin T/I, myeloperoxidase, NT-proBNP, miR-208b, miR-34a, and miR-150 in breast cancer patients receiving anthracyclines and/or trastuzumab to detect CRCD before any signs of overt cardiotoxicity are apparent.

Bilateral Triple-Negative Invasive Breast Cancer with a BRCA2 Mutation, and Glioblastoma: A Case Report and Literature Review.

Breast cancer is the second leading cause of death among women in North America. Glioblastoma is the most common primary malignant central nervous system tumor in adults. The majority of hereditary breast cancers are associated with deleterious mutations in the BRCA1 and BRCA2 genes. Although few case reports have described the incidence of glioblastoma in patients previously diagnosed with breast cancer, any association between BRCA2 mutations and glioblastoma has not been demonstrated to date. Herein, we report a woman who is a carrier of a familial BRCA2 mutation, and was previously diagnosed with triple-negative breast cancer (TNBC) and subsequently with a second primary TNBC and glioblastoma. Further investigation is required to define the possible relationship between these two aggressive malignances and the BRCA2 mutation, which might be critical for the proper management and treatment of this disease.

Prospect of the use of checkpoint inhibitors in hepatocellular cancer treatments.

Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%-3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC. The introduction of immune checkpoint inhibitors (cytotoxic T-lymphocyte antigen 4, programmed death 1, and programmed death-ligand 1) has opened a new horizon for cancer immunotherapy. Future direction in immunotherapy for HCC is to rationally combine it with other treatment modalities, including surgery, radiofrequency ablation, and cytotoxic agents, to maximize its therapeutic efficacy.