Changes in Citric Acid Cycle and Nucleoside Metabolism Are Associated with Anthracycline Cardiotoxicity in Patients with Breast Cancer

AbstractAnthracyclines and HER2-targeted antibodies are very effective for the treatment of breast cancer, but their use is limited by cardiotoxicity. In this nested case-control study, we assessed the role of intermediary metabolism in 38 women with breast cancer treated with anthracyclines and trastuzumab. Using targeted mass spectrometry to measure 71 metabolites in the plasma, we identified changes in citric acid and aconitic acid that differentiated patients who developed cardiotoxicity from those who did not. In patients with cardiotoxicity, the magnitude of change in citric acid at three  months correlated with the change in left ventricular ejection fraction (LVEF) and absolute LVEF at nine months. Patients with cardiotoxicity also demonstrated more pronounced changes in purine and pyrimidine metabolism. Early metabolic changes may therefore provide insight into the mechanisms as sociated with the development of chemotherapy-associated cardiotoxicity.
Source: Journal of Cardiovascular Translational Research - Category: Cardiology Source Type: research

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Publication date: Available online 15 August 2019Source: Carbohydrate PolymersAuthor(s): Yaping Wang, Junmin Qian, Ming Yang, Weijun Xu, Jinlei Wang, Guanghui Hou, Lijie Ji, Aili SuoAbstractCombination chemotherapy has attracted more and more attention in the field of anticancer treatment. Herein, a synergetic targeted combination chemotherapy of doxorubicin (DOX) and cisplatin in breast cancer was realized by HER2 antibody-decorated nanoparticles assembled from aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS). Cisplatin and DOX were successively conjugated onto AHA through chelation and Schiff’s base ...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
CONCLUSIONS: This multicentric retrospective study confirmed that sequential adjuvant therapy with anthracycline-based chemotherapy and paclitaxel for HER2 negative breast cancer is an effective and reliable regimen. PMID: 31424664 [PubMed - in process]
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
Abstract The transcriptional coactivator Amplified in Breast Cancer 1 (AIB1) plays a major role in the progression of hormone and HER2-dependent breast cancers but its role in triple negative breast cancer (TNBC) is undefined. Here, we report that established TNBC cell lines, as well as cells from a TNBC patient-derived xenograft (PDX) that survive chemotherapy treatment in vitro express lower levels of AIB1 protein. The surviving cell population has an impaired tube-formation phenotype when cultured onto basement membrane, a property shared with TNBC cells that survive shRNA-mediated depletion of AIB1 (AIB1LOW ce...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research
CONCLUSIONS: The most potential impact of TAILORx findings on practice change is for patients ≤ 50 years of age with RS of 16-25 who did not receive chemotherapy but may benefit. These findings may serve as a baseline for future analysis of practice patterns related to TAILORx. PMID: 31429016 [PubMed - as supplied by publisher]
Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Ann Surg Oncol Source Type: research
The objective of this analysis was to assess the pharmacokinetics of pertuzumab in combination with trastuzumab in Chinese patients with early breast cancer. Samples for pertuzumab and trastuzumab pharmacokinetic analysis were taken from Chinese patients during cycle 1 of treatment and at steady-state in cycle 10. Noncompartmental analysis was used to estimate minimum and maximum serum concentrations (Cmax and Cmin), area under the concentration-time curve, clearance, and other pharmacokinetic parameters. In 15 patients, mean steady-state Cmax and Cmin pertuzumab serum concentrations (368 ± 177 μg/ml, and 122 &pl...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Clinical Papers Source Type: research
Abstract BACKGROUND: Immune checkpoint inhibitors are active in a broad range of cancers, including programmed death ligand 1 (PD-L1)-positive, triple-negative, metastatic breast cancer (MBC). Antibody-dependent cell-mediated cytotoxicity is a mechanism of action of trastuzumab. We performed a phase Ib trial of durvalumab and trastuzumab in HER2-positive MBC previously treated with chemotherapy and anti-HER2 antibodies to assess safety, efficacy, and correlative endpoints. PATIENTS AND METHODS: Patients with HER2-positive MBC were enrolled on a standard 3 + 3 design. Dose level 1 was durvalumab (1,125 mg intr...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Conclusions: Collagen degradation markers are associated with response to neoadjuvant therapy and seem to play a role in breast cancer.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conditions:   Bilateral Breast Carcinoma;   Breast Carcinoma;   HER2/Neu Negative;   Mastectomy Patient;   Recurrent Breast Carcinoma;   Triple-Negative Breast Carcinoma Interventions:   Drug: ATR Kinase Inhibitor M6620;   Other: Quality-of-Life Assessment;   Other: Questionnaire Administration;   Radiation: Radiation Therapy Sponsor:   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
The present study aimed to examine the factors affecting survival of female patients with inflammatory breast cancer (IBC), as well as to construct and validate a nomogram to predict overall survival in IBC. AbstractIn the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models w...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Authors: Weiss J, Glode A, Messersmith WA, Diamond JR Abstract Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan. Areas covered: This review covers the m...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
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