CYP2D6 testing in breast cancer: ready for prime time?

Despite recent advances in hormonal therapy for breast cancer, tamoxifen remains a major therapeutic option, with indications ranging from primary prevention to metastatic disease. Understanding the variation in response to tamoxifen may significantly improve our ability to personalize cancer care and maximize therapeutic efficacy. One area of particular interest is the impact of cytochrome P450 CYP2D6 genetic polymorphisms on tamoxifen metabolism.

EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance.

Glioblastoma, GBM, is the most frequent brain malignancy in adults. Patients with these tumors survive only, approximately, one year after diagnosis and rarely survive beyond two years. This poor prognosis is, in part, due to our insufficient understanding of the complex aggressive nature of these tumors and the lack of effective therapy.

Prediction of survival following first-line chemotherapy in men with castration-resistant metastatic prostate cancer.

Purpose: We sought to evaluate predictors of overall survival following progression after systemic chemotherapy in men with metastatic castration-resistant prostate cancer.

Experimental Design: For our study population, we used the TAX327 multicenter randomized phase III trial comparing administration of docetaxel and prednisone every 3 weeks, weekly administration of docetaxel and prednisone, and administration of mitoxantrone and prednisone every 3 weeks. Progression was defined as the earliest of prostate-specific antigen (PSA), tumor, or pain progression.

The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival.

Aims Of The Study: There are no known predictive factors of response in men receiving chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). We investigated pre-treatment factors that predicted a 30% PSA decline (30% PSAD) within 3 months of starting chemotherapy, and assessed performance of a risk group classification in predicting PSA declines and overall survival (OS) in men with mCRPC.

Methods: In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline within 3 months.

Do patient attributes predict oncologist empathic responses and patient perceptions of empathy?

Purpose: Most patients with advanced cancer experience negative emotion. When patients express emotions, oncologists rarely respond empathically. Oncologists may respond more empathically to some patients, and patients may perceive different levels of empathy and trust given past documentation of disparities in cancer care.

Thromboprophylaxis with low-molecular-weight heparin in medical patients with cancer.

Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents.

Reliable data on 5- and 10-year survival provide accurate estimates of 15-year survival in estrogen receptor-positive early-stage breast cancer.

There are few studies of model-based survival projections using early empirical results for estimating long-term survival. Utilizing Early Breast Cancer Trialists' Collaborative Group (EBCTCG) data, a Markov model was generated to compare empirical results with those modeled beyond the empirical result time horizon in estrogen receptor (ER)-positive early-stage breast cancer (ESBC). Modeling 15-year survival based on 5- and 10-year EBCTCG data resulted in an average error estimate in breast cancer mortality of 0.

MYC activity mitigates response to rapamycin in prostate cancer through eukaryotic initiation factor 4E-binding protein 1-mediated inhibition of autophagy.

Loss of PTEN and activation of phosphoinositide 3-kinase are commonly observed in advanced prostate cancer. Inhibition of mammalian target of rapamycin (mTOR), a downstream target of phosphoinositide 3-kinase signaling, results in cell cycle arrest and apoptosis in multiple in vitro and in vivo models of prostate cancer. However, single-agent use of mTOR inhibition has limited clinical success, and the identification of molecular events mitigating tumor response to mTOR inhibition remains a critical question.

Impact of venous thromboembolism and anticoagulation on cancer and cancer survival.

Changes in the hemostatic system and chronic hemostatic activation are frequently observed in patients with cancer, even in the absence of venous thromboembolism (VTE). VTE is a leading cause of death among patients with cancer and contributes to long-term mortality in patients with early as well as advanced-stage cancer. Mounting evidence suggests that components of the clotting cascade and associated vascular factors play an integral part in tumor progression, invasion, angiogenesis, and metastasis formation.

Evolution of HIV-1 in a patient population failing multiple-drug therapy.

To understand the evolutionary pathway of the multi-drug-resistant virus HIV-1 under drug-induced selection pressure, plasma from seven patients from baseline to different intervals post-treatment failure were used in RT-PCR protocols. Multiple clones were sequenced for each time point. Drug-resistant mutations were detected in five patients.

Using surrogate biomarkers to predict clinical benefit in men with castration-resistant prostate cancer: an update and review of the literature.

Recurrent prostate cancer has a complex molecular etiology and a prolonged disease course. Although initially responsive to androgen ablation, many men eventually become castration resistant, develop skeletal metastases, and are palliatively treated with docetaxel-based chemotherapy, radiation therapy, bisphosphonates, and best supportive care. Given the modest success rates of the current standard of care, clinical trial enrollment is encouraged.

Poor documentation prevents adequate assessment of quality metrics in colorectal cancer.

To standardize oncology clinical practice and improve patient outcomes, multiple organizations have developed cancer-specific metrics on the basis of a systematic background review, expert guidance, and fundamental elements of cancer care-staging and treatment.

A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer.

Objectives: The appropriate sequencing of chemotherapy and radiation for the treatment of advanced endometrial cancer has not yet been determined. We sought to evaluate the outcome and adverse effects in patients with advanced stage endometrial cancer treated with postoperative chemotherapy and radiation to determine whether there was an advantage to a particular sequencing modality.

Methods: A multicenter retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1993 to 2007 was conducted.

Cost-effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the United States.

Background: Prophylaxis with granulocyte colony-stimulating factor reduces the risk for febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy.

Objective: We estimated the incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 of chemotherapy) with pegfilgrastim versus filgrastim in women with early-stage breast cancer receiving myelosuppressive chemotherapy in the United States.

Methods: A decision-analytic model was constructed from a health payer's perspective with a lifetime study horizon.

Cancer and thrombosis: back to the future renewed interest in an old problem.

Cancer patients are at increased risk for thromboembolic complications due to the release of procoagulants, compression or invasion of blood vessels and the reduced mobility associated with cancer and cancer treatment. This has led to recommendations for thromboprophylaxis in hospitalized medical and surgical cancer patients and extended prophylaxis in cancer patients experiencing a venous thromboembolism. Routine prophylactic anticoagulation is not currently recommended in ambulatory cancer patients except in very high risk settings.

Improved surgical outcomes for breast cancer patients receiving neoadjuvant aromatase inhibitor therapy: results from a multicenter phase II trial.

Background: Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer. A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice.

Study Design: One hundred fifteen postmenopausal women with >2 cm, estrogen receptor (ER) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.

Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration.

We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and alpha- and gamma-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt).

Adherence to nicotine replacement therapy among pregnant smokers.

Introduction: This secondary analysis examined the association between adherence to nicotine replacement therapy (NRT) and smoking cessation among pregnant smokers enrolled in Baby Steps, an open-label randomized controlled trial testing cognitive-behavioral therapy (CBT) versus CBT plus NRT.

Method: The analysis included only women who received NRT for whom we had complete data (N = 104). Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation.

Genomic strategy for targeting therapy in castration-resistant prostate cancer.

Purpose: Despite treatments which lower circulating androgens, advanced prostate cancers often maintain androgen receptor (AR) signaling. The variable response to secondary hormonal manipulations in men with castrate-resistant prostate cancer (CRPC) creates a compelling need for strategies to individualize therapy based on the molecular features of each patient's tumor.

Methods: A transcription-based AR activity signature was developed from an androgen-sensitive prostate cancer cell (LNCaP) and tested on independent data sets of prostate cancer cell lines and human tumors to assess its precision and accuracy in detecting AR activity.

Tyrosine phosphorylation of the human glutathione S-transferase P1 by epidermal growth factor receptor.

Epidermal growth factor receptor (EGFR) gene amplification, mutations, and/or aberrant activation are frequent abnormalities in malignant gliomas and other human cancers and have been associated with an aggressive clinical course and a poor therapeutic outcome. Elevated glutathione S-transferase P1 (GSTP1), a major drug-metabolizing and stress response signaling protein, is also associated with drug resistance and poor clinical outcome in gliomas and other cancers. Here, we provide evidence that GSTP1 is a downstream EGFR target and that EGFR binds to and phosphorylates tyrosine residues in the GSTP1 protein in vitro and in vivo.

Persistent smoking after a diagnosis of lung cancer is associated with higher reported pain levels.

Unlabelled: The purpose of this study was to evaluate the impact of smoking status after a diagnosis of lung cancer on reported pain levels. We conducted a telephone survey of patients with lung cancer identified from 4 participating sites between September 2004 and July 2006. Patients were asked to rate their usual pain level over the past week on a 0 to 10 rating scale on which 0 was "no pain" and 10 "pain as bad as you can imagine.