Pharmacogenomics, CYP2D6, and Tamoxifen: A Survey of the Reasons Sustaining European Clinical Practice Paradigms.

Tamoxifen is a drug that is often used in the clinical management of breast cancer. CYP2D6 is a key metabolizing enzyme that is involved in the conversion of tamoxifen to its active drug metabolites. CYP2D6 has several alleles that metabolize tamoxifen and other drugs at different rates that can alter therapeutic impact, a characteristic that renders it one of the most studied enzymes in the field of pharmacogenetics. Background and objectives: Portugal has no implemented measures based on pharmacogenomics analysis prior to therapy that might function as a cultural sample control when analyzing the individual and economic factors present in clinical practice paradigms. Therefore, we aim to investigate the impact of CYP2D6 genotyping of the tamoxifen metabolizing enzymes in the clinical management of breast cancer patients. Materials and Methods: Qualitative/quantitative studies regarding the impact of pharmacogenomics in breast cancer; personal interviews in different Portuguese laboratories within hospital setting using a survey. Analysis of data through interviews to management board and/or decision makers from major oncological centers. Results: Reasons for common adoption of pharmacogenomics practice are contradictory and based both in economic factors and cultural/clinical bias. Conclusions: This research study identifies specific cultural and/or clinical bias that act as obstacles to pharmacogenomic implementation and proposes viable courses of action that might bring about change in cultural/medical habits.

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations.

Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.

Using a population-based cancer registry for recruitment in a pilot cancer control study.

Cancer control investigations in the United States rarely use population-based registries as a resource for recruitment. A placebo-controlled, double-blind, randomized toxicity trial of tamoxifen was conducted among postmenopausal women with node negative breast cancer. To achieve the accrual goal of 140 subjects in this single institution study, the Wisconsin Cancer Reporting System (WCRS), a population-based cancer registry, was used. Registry information from the last 9 years was used to identify 3,585 women who met the study criteria with respect to age, stage, and previous therapy. The vital status of identified women was confirmed using Wisconsin state death records. For identified cases, rosters were prepared and sent to the physician with a cover letter and study description. The physicians were asked to update the list and, if appropriate, to sign letters to potentially eligible and interested women. Thirty-eight percent of women receiving a letter and study information from their physicians contacted the study office about participation. Eighteen months from its initiation, 140 women were entered on study. This successful use of a population-based cancer registry illustrates an efficient recruitment method which could be modified for other cancer control/chemoprevention trials.