Annals of oncology : official journal of the European Society for Medical Oncology
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Letter Case Reports
Carcinomas of an unknown primary site: a curable disease?
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Anthracycline-trastuzumab-containing regimens demonstrate significant clinical activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, the utility of this strategy is limited by unacceptably high rates of significant cardiotoxicity, particularly with concurrent administration. Anthracycline-induced cardiotoxicity is thought to be mediated primarily through increased myocardial oxidative stress, modified partly by the activity of neuregulins. Trastuzumab-induced cardiotoxicity is thought to be mediated by the ErbB/neuregulin system, with exposure to trastuzumab partly blocking the protective effect of neuregulins on the myocardium. ⋯ The use of less cardiotoxic anthracyclines may be one strategy to lessen the risk of cardiotoxicity. Liposomal doxorubicin products offer similar efficacy compared with conventional doxorubicin, with significantly less cardiotoxicity, and have been successfully used in combination with trastuzumab in the metastatic and neo-adjuvant setting. Clinical trials are currently underway to assess the safety of pegylated liposomal doxorubicin during concurrent administration with trastuzumab compared with standard sequential treatment using conventional doxorubicin in the adjuvant setting.
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Women with triple-negative (TN) breast cancer are at increased risk of distant metastases and have reduced survival versus other breast cancer patients. Relative survival of women with TN breast cancer who develop brain metastases is unknown. ⋯ Patients with TN disease were more likely to develop distant metastases earlier than non-TN patients, developed brain metastases sooner, and had shorter overall survival.