Model-Based Quantification of Impact of Genetic Polymorphisms and Co-Medications on Pharmacokinetics of Tamoxifen and Six Metabolites in Breast Cancer.

Variations in clinical response to tamoxifen (TAM) may be related to polymorphic cytochromes P450 (CYPs) involved in forming its active metabolite endoxifen (ENDO). We developed a population pharmacokinetic (PopPK) model for tamoxifen and six metabolites to determine clinically relevant factors of ENDO exposure. Concentration-time data for TAM and 6 metabolites come from a prospective, multicenter, 3-year follow-up study of adjuvant TAM (20 mg/day) in patients with breast cancer, with plasma samples drawn every 6 months, and genotypes for 63 genetic polymorphisms (PHACS study, NCT01127295).

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.

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 alpha- and beta-tubulin, classes II to IV beta-tubulin isotypes, and tau protein was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded tumors from the primary breast cancer.

Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in women worldwide. Elderly individuals make up a large part of the breast cancer population, and there are important specific considerations for this population. The International Society of Geriatric Oncology created a task force to assess the available evidence on breast cancer in elderly individuals, and to provide evidence-based recommendations for the diagnosis and treatment of breast cancer in such individuals.

Chemobrain: is systemic chemotherapy neurotoxic?

Purpose Of Review: The existence of chemobrain has become almost universally accepted, although many details of the concept are controversial. Data about the different types of cognitive impairment and their duration are not always consistent in the literature. We still do not know which cytotoxic agents are responsible, which characteristics make patients vulnerable, and which biologic mechanisms are involved.

Progress and new standards of care in the management of HER-2 positive breast cancer.

The aim of this review article is to examine the available evidence regarding diagnosis and treatment of HER-2 positive breast cancer. This group of breast tumours (up to 30% of the total number of breast cancers) is known for having a more aggressive behaviour. The current recommendations for HER-2 positive tumour diagnosis are discussed since accurate identification of HER-2 amplification or overexpression is key for allowing a correct risk assessment and treatment.

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.

Potential predictive value of Bcl-2 for response to tamoxifen in the adjuvant setting of node-positive breast cancer.

Approximately 50% of patients with estrogen receptor (ER)-positive breast cancer (BC) and 70%-80% of patients with ER-positive and progesterone receptor (PgR)-positive BC respond to hormonal therapy. Additional predictive markers are needed. A group of 287 patients with ER- and/or PgR-positive tumors was selected from 804 patients previously enrolled in a multicenter phase III trial.

Facts and controversies in systemic treatment of metastatic breast cancer.

The management of metastatic breast cancer remains an important and controversial issue. The systemic therapy, comprising endocrine, cytotoxic and biological agents, can be administered sequentially or in combination. Few drugs or combinations provide a significant improvement in survival and, therefore, in the great majority of cases, treatment is given with a palliative intent.

Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study.

Docetaxel is currently one of the most active agents for breast cancer. Predictive markers of docetaxel efficacy are clearly needed in order to avoid unnecessary toxicity in nonresponding or resistant patients and to improve the cost-effectiveness ratio of docetaxel. This pilot study correlates the clinical efficacy of docetaxel in 54 metastatic or locally advanced breast cancer patients with the expression of microtubule-associated parameters evaluated by immunohistochemistry in archival tumor samples.

Metastatic melanoma: chemotherapy.

The incidence of cutaneous melanoma has been rapidly increasing, with an estimate of 47,700 new cases diagnosed in 2000 in the United States. In the early phase of its natural history, melanoma is cured in most cases by surgery, but once the metastatic phase develops, it is almost always fatal. The treatment of metastatic melanoma remains unsatisfactory.