Clinical breast cancer
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Clinical breast cancer · Oct 2008
Cardiac morbidity and mortality after breast conservation treatment in patients with early-stage breast cancer and preexisting cardiac disease.
This study was undertaken to determine the risk of late cardiac morbidity and mortality in patients with preexisting cardiac disease treated with contemporary radiation techniques for early-stage breast cancer. ⋯ Although OS was similar in both groups, radiation was associated with a higher incidence of cardiac death in patients with left-sided breast cancer. Efforts should be made to minimize cardiac exposure and also to promote more vigilant risk factor modification in this group of women.
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Clinical breast cancer · Aug 2008
ReviewAdjuvant trastuzumab therapy for HER2-positive breast cancer.
HER2 is overexpressed or gene amplified in 20%-25% of breast cancers. The anti-HER2 monoclonal antibody trastuzumab targets HER2-positive tumors, inhibiting proliferation and inducing cell death via extracellular and intracellular mechanisms. The clinical benefits observed with trastuzumab in the metastatic setting provided the rationale for assessing trastuzumab in the treatment of early breast cancer. ⋯ Risk factors associated with cardiac dysfunction included baseline left ventricular ejection fraction level, hypertension, and older age. The addition of trastuzumab to adjuvant chemotherapy provides significant survival benefits with a positive benefit/risk ratio. Ongoing and planned trials correlated with basic science will enhance our understanding of HER2-positive disease, leading to treatment optimization and further improvements in patient outcomes.
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Clinical breast cancer · Jun 2008
Phase I/II study of ixabepilone plus capecitabine in anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer.
The aim of this study was to determine the safety, maximum tolerated dose (MTD), recommended phase II dose, and efficacy of the epothilone B analogue ixabepilone plus capecitabine in anthracycline-pretreated/ resistant and taxane-resistant metastatic breast cancer (MBC). ⋯ Ixabepilone plus capecitabine demonstrated clinical activity and an acceptable safety profile in patients with anthracycline-pretreated/resistant and taxane-resistant MBC. Ixabepilone was recently approved in the United States for the treatment of resistant/refractory locally advanced or MBC.
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Clinical breast cancer · Apr 2008
Multicenter StudyPhase II trial of gemcitabine/carboplatin (plus trastuzumab in HER2-positive disease) in patients with metastatic breast cancer.
Gemcitabine and carboplatin have significant preclinical synergy, and both provide synergistic antitumor activity in metastatic breast cancer (MBC) when used in combination with trastuzumab. The gemcitabine/ cisplatin combination is highly active in MBC with response rates (RRs) of approximately 50% in anthracycline- and taxane-pretreated patients and up to 80% in untreated subjects. This phase II trial studied the efficacy and safety of gemcitabine/carboplatin with or without trastuzumab in patients with MBC. ⋯ Gemcitabine/carboplatin/trastuzumab is highly active in patients with HER2-positive MBC. Gemcitabine/carboplatin is active in patients with HER2-negative MBC independent of previous taxane therapy. Gemcitabine/carboplatin with or without trastuzumab administered every 2 weeks is associated with a low frequency of serious toxicity.
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Clinical breast cancer · Mar 2008
ReviewCardiac toxicity of ErbB2-targeted therapies: what do we know?
The potential for cardiac toxicity in association with targeted biologic agents was first observed with trastuzumab, a monoclonal antibody that targets the ErbB2/HER2 receptor. In the pivotal trial of trastuzumab in ErbB2-positive metastatic cancer, an increased incidence of serious cardiac events was observed, particularly when trastuzumab was administered in combination with anthracyclines. The ErbB2 receptor is expressed on cardiomyocytes, in addition to tumor tissue, where it exerts a protective effect on cardiac function; thus, interference with ErbB2-signaling may block this protective effect. ⋯ In a comprehensive analysis of cardiac safety data from all lapatinib trials completed to date, which included 3558 healthy volunteers and patients with a variety of solid cancers on 43 trials, the overall incidence of left ventricular ejection fraction declines was 1.6%, with 0.2% of patients experiencing symptomatic CHF. Risk factors that might predict for cardiac dysfunction with ErbB2-targeted therapy are actively under investigation and will aid in the identification of at-risk populations and in the development of strategies for risk minimization in the future. It is important to note that, while careful cardiac monitoring is required for all patients receiving ErbB2-targeted therapy in any disease setting, the overall impact of these agents on the outcomes of patients with ErbB2-positive breast cancer has been dramatic and positive.