Anthracyclines in the treatment of patients with early breast cancer.
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ABSTRACT:
SUBMITTER: Guarneri V
PROVIDER: S-EPMC9271479 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Anthracyclines in the treatment of patients with early breast cancer.
ESMO open 20220419 3
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Project description:Standard chemotherapy for early breast cancer consists generally of an anthracycline - taxane - based regimen, preferably in sequence. Anthracyclines are among the most active cytotoxic drugs against breast cancer. Nevertheless, benefits attained by the use of the more potent anthracycline schedules must be balanced against increased short - and long - term toxicity, and treatment options must be individualized for each patient. Authors review available data regarding anthracycline efficacy and toxicity in the early breast cancer setting and the potential directions for future research.
| S-EPMC9289865 | biostudies-literature
Project description:BackgroundSarcopenia refers to the reduction of both volume and number of skeletal muscle fibers. Lean body mass loss is associated with survival, quality of life and tolerance to treatment in cancer patients. The aim of our study is to analyse the association between toxicities and sarcopenia in early breast cancer patients receiving adjuvant treatment.Materials and methodsBreast cancer patients who have received anthracycline-based adjuvant treatment were retrospectively enrolled. CT scan images performed before, during and after adjuvant chemotherapy were used to evaluate lean body mass at third lumbar vertebra level with the software Slice Omatic V 5.0.Results21 stage I-III breast cancer patients were enrolled. According to the skeletal muscle index at third lumbar vertebra cut-off ≤38.5 cm2/m2, 8 patients (38.1%) were classified as sarcopenic before starting treatment, while 10 patients (47.6%) were sarcopenic at the end of treatment. A lower baseline L3 skeletal muscle index is associated with G3-4 vs G0-2 toxicities (33.4 cm2/m2 (31.1-39.9) vs 40.5 cm2/m2 (33.4-52.0), p = 0.028). Similarly skeletal muscle cross sectional area was significantly lower in patients with G3-4 toxicities (86.7 cm2 (82.6-104.7) vs 109.0 cm2 (83.3-143.9), p = 0.017). L3 skeletal muscle index is an independent predictor of severe toxicity (p = 0.0282) in multivariate analysis.ConclusionLean body mass loss is associated with higher grade of toxicity in early breast cancer patients receiving adjuvant chemotherapy.
| S-EPMC5986630 | biostudies-literature
Project description: Not available
| S-EPMC6378927 | biostudies-literature
Project description:Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-alpha (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. Here we describe in details the contents and quality controls for the gene expression and clinical data associated with the study published by Desmedt and colleagues in the Journal of Clinical Oncology in 2011 (Desmedt et al., 2011). We also provide R code to easily access the data and perform the quality controls and basic analyses relevant to this dataset.
| S-EPMC4608867 | biostudies-literature
Project description:BackgroundAnthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.ObjectivesThe objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010) and EMBASE (1980 to November 2010) databases. In addition, we handsearched reference lists, conference proceedings of the International Society of Paediatric Oncology (SIOP) and American Society of Clinical Oncology (ASCO) meetings (1998 to 2010) and ongoing trials registers.Selection criteriaRandomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional therapy or placebo in cancer patients (children and adults) receiving anthracyclines.Data collection and analysisTwo review authors independently performed the study selection, risk of bias assessment and data extraction including adverse effects.Main resultsWe identified RCTs for the eight cardioprotective agents N-acetylcysteine, phenethylamines, coenzyme Q10, a combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol, amifostine and dexrazoxane (mostly for adults with advanced breast cancer). All studies had methodological limitations and for the first seven agents there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The 10 included studies on dexrazoxane enrolled 1619 patients. The meta-analysis for dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (risk ratio (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control groups. The results for adverse effects were ambiguous. No significant difference in the occurrence of secondary malignancies was identified.Authors' conclusionsNo definitive conclusions can be made about the efficacy of cardioprotective agents for which pooling of results was impossible. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control groups was identified. The evidence available did not allow us to reach any definite conclusions about adverse effects. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects for each individual patient.
| S-EPMC6457676 | biostudies-literature
Project description:Pre-surgical treatments in patients with early breast cancer allows a direct estimation of treatment efficacy, by comparing the tumor and the treatment. Patients who achieve a pathological complete response at surgery have a better prognosis, with lower risk of disease recurrence and death. Hence, clinical research efforts have been focusing on high-risk patients with residual disease at surgery, who may be "salvaged" through additional treatments administered in the post-neoadjuvant setting. In the present review, we aim to illustrate the development and advantages of the post-neoadjuvant setting, and to discuss the available strategies for patients with early breast cancer, either approved or under investigation. This review was written after literature search on main scientific databases (e.g., PubMed) and conference proceedings from major oncology conferences up to 1 August 2022. T-DM1 and capecitabine are currently approved as post-neoadjuvant treatments for patients with HER2-positive and triple-negative breast cancer, respectively, with residual disease at surgery. More recently, other treatment strategies have been approved for patients with high-risk early breast cancer, including the immune checkpoint inhibitor pembrolizumab, the PARP inhibitor olaparib and the CDK 4/6 inhibitor abemaciclib. Novel agents and treatment combinations are currently under investigation as promising post-neoadjuvant treatment strategies.
| S-EPMC9654353 | biostudies-literature
Project description:BackgroundAlthough trastuzumab and anthracyclines are frequently used to treat breast cancer (BC) and gastric cancer (GC), cardiotoxicity is a serious concern. The cardiac function assessment is recommended at baseline before initiating treatment. However, the prevalence rates of baseline cardiac checkups are unknown.MethodsThe national database of hospital-based cancer registries linked to the health services-utilization data was used to study patients with newly diagnosed stage IV BC and GC (n = 6271) who received trastuzumab (n = 4324, 69.0%) or anthracyclines between January 2012 and December 2015. The baseline ultrasound echocardiogram (UCG) performance rate and factors related to adequate UCG performance for all patients and those receiving trastuzumab were analyzed.ResultsThe adequate baseline UCG checkup rate was higher in patients treated with trastuzumab than in those treated with anthracyclines (71.8% vs 44.1%, respectively). Additionally, patients with GC were less likely to receive an adequate baseline UCG performance than those with BC (70.4% vs 75.0%, respectively). After adjusting for potential confounders, patients with anthracycline-treated BC and GC were less likely to receive adequate baseline UCG performance than those with trastuzumab-treated BC (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.20-0.28, and OR: 0.07, 95% CI: 0.03-0.16, respectively). Furthermore, patients with trastuzumab-treated GC were less likely to receive adequate baseline UCG performance than those with BC (OR: 0.65, 95% CI: 0.50-0.84).ConclusionsThe baseline UCG was less likely to be performed in patients receiving anthracyclines than in those receiving trastuzumab, as well as in patients with GC than in those with BC.
| S-EPMC9844617 | biostudies-literature
Project description:Doxorubicin (DOX), a commonly used anticancer agent, causes cardiotoxicity that begins with the first dose and may progress to heart failure years after treatment. An inflammatory response associated with neutrophil recruitment has been recognized as a mechanism of DOX-induced cardiotoxicity. This study aimed to validate mRNA expression of the previously identified biomarkers of DOX-induced cardiotoxicity, PGLYRP1, CAMP, MMP9, and CEACAM8, and to assay their protein expression in the peripheral blood of breast cancer patients. Blood samples from 40 breast cancer patients treated with DOX-based chemotherapy were collected before and after the first chemotherapy cycle and > 2 years after treatment. The protein and gene expression of PGLYRP1/Tag7, CAMP/LL37, MMP9/gelatinase B, and CEACAM8/CD66b were determined using ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each candidate biomarker. Patients with cardiotoxicity (n = 20) had significantly elevated levels of PGLYRP1, CAMP, MMP9, and CEACAM8 at baseline, after the first dose of DOX-based chemotherapy, and at > 2 years after treatment relative to patients without cardiotoxicity (n = 20). The first dose of DOX induced significantly higher levels of all examined biomarkers in both groups of patients. At > 2 years post treatment, the levels of all but MMP9 dropped below the baseline. There was a good correlation between the expression of mRNA and the target proteins. We demonstrate that circulating levels of PGLYRP1, CAMP, MMP9, and CEACAM8 can predict the cardiotoxicity of DOX. This novel finding may be of value in the early identification of patients at risk for cardiotoxicity.
| S-EPMC11395913 | biostudies-literature
Project description:BackgroundDuplication of the centromeric region of chromosome 17 (Ch17CEP) is associated with sensitivity to anthracyclines. An explanation may be chromosome instability (CIN); a frequent event in solid tumours associated with poor outcome. The predictive value of CIN seems to be drug dependent and CIN has been associated with both sensitivity and resistance to chemotherapy.MethodsIn this study, we used fluorescent in situ hybridisation for chromosomes 1, 7, 11, 17 and 18 to identify patients with high tumour CIN% in 322 patients recruited into the BR9601 clinical trial.ResultsHigh tumour CIN% was correlated to Ch17CEP (P=3.68e-7) and is associated with a reduced RFS (P=0.0011) and OS (P=0.04). Patients with high CIN had a decreased risk of death on E-CMF compared with CMF.ConclusionCIN is of prognostic significance and may be of predictive value in determining anthracycline response, although further testing is required.
| S-EPMC3389422 | biostudies-literature
Project description:Background:Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time. Methods:After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection. Results:Thirty-two female patients (aged 57±13 years) with pre-treatment haematocrit 38%±4%, and ejection fraction 64%±6% were analysed. Pre-treatment mECV was 27.0%±2.9% at 1 min, and 26.4%±3.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%±4.9%, and 30.0%±5.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%±4.5%, and 27.7%±3.7%, respectively, without significant differences (P>0.548) when compared to post-treatment values. Conclusions:mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients' clinical workflow.
| S-EPMC7242290 | biostudies-literature