Chantal Bernard-Marty

Monoclonal antibody-based targeted therapy in breast cancer : current status and future directions

The recent development of monoclonal antibodies targeting growth factor receptors in cancer treatment represents a milestone for both researchers and physicians. Advances in the understanding of key molecular pathways for tumour growth and survival have facilitated the development of these targeted therapies, in particular in breast cancer. This review focuses on the three most important recombinant humanised monoclonal antibodies that have shown activity in women with breast cancer: trastuzumab, pertuzumab and bevacizumab. Trastuzumab, an anti-erbB2 (human epidermal growth factor receptor) monoclonal antibody, is currently routinely used in both the metastatic and adjuvant settings for patients with erbB2-positive tumours. Pertuzumab, a monoclonal antibody binding to a different epitope on erbB2 than trastuzumab, is under early clinical evaluation. This drug has been developed for breast cancer patients, whether overexpressing erbB2 or not. Bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor-A, is being evaluated in the metastatic setting for its antiangiogenic properties, and is showing promising results.

Class III beta-tubulin isotype predicts response in advanced breast cancer patients randomly treated either with single-agent doxorubicin or docetaxel.

Purpose: To evaluate the role of microtubule-associated variables as potential predictors of response and clinical outcome in patients with advanced breast cancer receiving single-agent docetaxel or doxorubicin chemotherapy. Experimental Design: The analysis was done on 173 tumor samples from patients with locally advanced or metastatic breast cancer who have participated in the TAX-303 phase III trial in which patients were randomly assigned to receive docetaxel or doxorubicin. Expression of total α- and β-tubulin, classes II to IV β-tubulin isotypes, and τ protein was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded tumors from the primary breast cancer. Results: We observed that patients with “high” expression of class III β-tubulin isotype had a higher probability of response to docetaxel than to doxorubicin treatment (odds ratio, 1.9; 95% confidence interval, 1.01-3.7; P = 0.05). No difference was observed in terms of time to progression or in terms of overall survival. Conclusions: This study suggests that the superiority of docetaxel over doxorubicin seems to be confined to the subgroup of patients with “high” expression of class III β-tubulin isotype.

Use and abuse of taxanes in the management of metastatic breast cancer.

Taxanes are currently introduced early in the treatment of patients with metastatic breast cancer (MBC), both as single agents and in combination with anthracyclines. Two different patient populations exist: those with no or minimal prior anthracycline exposure and those who have failed previous anthracyclines. The data generated through phase III trials in first-line MBC therapy will be reviewed and their interpretation for routine clinical practice (use versus abuse) will be discussed. Ways of improving taxane-based treatment tailoring both in the pre- and postgenomic eras will be addressed.

Management of head and neck cancer in elderly patients.

Head and neck cancer (HNC) represents a heterogeneous group of tumours requiring multimodality approaches. It is debatable whether HNC treatment in geriatric patients should be different to that delivered for younger patients. Furthermore, the risk of death seems to be higher in HNC patients with higher co-morbidity status. Despite the fact that there is no significant difference in outcome in younger versus older patients, older HNC patients are more likely to receive nonstandard, less aggressive therapies than younger patients. Age alone should not be the basis for selecting treatment options in older HNC patients. A thorough pretreatment evaluation of co-morbidities should always be performed, and radical surgical options should not be excluded in older HNC patients treated with curative intent, as postoperative complications occur no more frequently in older patients than in younger patients. Locoregional control and disease-free survival in older patients treated with radiation therapy (either with curative intent or in the palliative setting) are comparable to the results seen in younger HNC patients, with the same acute toxicity profile. In patients receiving systemic therapies, special attention must be given to modification of chemotherapy dosages according to renal and hepatic function. Molecular-targeted therapies appear to be very useful in such patients because of their favourable tolerability. In conclusion, once all physiological and biological risk factors have been addressed, a large proportion of geriatric patients can and should be offered the same HNC treatment as is offered to younger patients.