Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future?

BACKGROUND: Despite current trend of targeted therapy development, cytotoxic agents are a mainstay of treatment of patients with breast cancer. We reviewed recent advances in cytotoxic therapy for patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: Medline searches were conducted for English language studies using the term 'MBC' and 'cytotoxic drugs'. The data search was restricted to the period 2000-2011. RESULTS: Several novel cytotoxic compounds, all microtubule inhibitors, have been approved for clinical use in MBC: (i) nab-paclitaxel, reported to improve tumour response and decrease hypersensitivity reactions in comparison with other taxanes; (ii) ixabepilone, shown to have clinical benefit in taxane- and anthracycline-resistant disease and (iii) eribulin, shown to improve overall survival in heavily pre-treated patients, when compared with best available standard treatment. Agents, such as larotaxel, vinflunine, trabectidin and formulations, including cationic liposomal paclitaxel or paclitaxel poliglumex, are currently under evaluation in phase II/III trials. CONCLUSION: Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with MBC. Further research into new cytotoxic compounds is needed in order to maximise benefit, whilst minimising toxicity.

Tumour dormancy and clinical implications in breast cancer.

The aim of adjuvant therapy in breast cancer is to reduce the risk of recurrence. Some patients develop metastases many years after apparently successful treatment of their primary cancer. Tumour dormancy may explain the long time between initial diagnosis and treatment of cancer, and occurrence of relapse. The regulation of the switch from clinical dormancy to cancer regrowth in locoregional and distant sites is poorly understood. In this review, we report some data supporting the existence of various factors that may explain cancer dormancy including genetic and epigenetic changes, angiogenic switch, microenvironment, and immunosurveillance. A better definition and understanding of these factors should allow the identification of patients at high risk of relapse and to develop new therapeutic strategies in order to improve prognosis.