Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment

Abstract Background Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study. Methods Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication. Results A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P < 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6. Conclusions CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact

Multiple Gastrointestinal Symptoms Are Associated With Chemotherapy-Induced Nausea in Patients With Breast Cancer

BackgroundUnrelieved chemotherapy-induced nausea (CIN) is a significant problem for patients with breast cancer (BC).ObjectiveIn a sample of patients with BC who were assessed before their second or third cycle of chemotherapy, study purposes were to evaluate for the occurrence, severity, frequency, and distress associated with CIN; evaluate for differences in demographic and clinical characteristics and gastrointestinal (GI) symptom occurrence rates between patients who did and did not report CIN; and determine which demographic, clinical, and symptom characteristics were associated with the occurrence of CIN.MethodsPatients completed demographic and clinical questionnaires and the Memorial Symptom Assessment Scale for nausea and common GI symptom assessments. Univariate analyses evaluated for differences in demographic and clinical characteristics and GI symptom occurrence between patients who did and did not report CIN. Multiple logistic regression analysis evaluated for characteristics associated with CIN.ResultsOf the 532 patients with BC, 47.2% reported CIN occurrence. Characteristics associated with CIN group membership were poorer functional status, receipt of chemotherapy on a 14-day cycle, and higher occurrence rates of 5 GI symptoms (ie, dry mouth, vomiting, constipation, change in the way food tastes, and lack of appetite; all P < .001).ConclusionsUnrelieved CIN is a common symptom in patients with BC. This study is the first to demonstrate that 5 co-occurring GI symptoms were associated with CIN occurrence.Implications for practiceThis study identified new risk factors for CIN occurrence in patients with BC. Clinicians may be able to initiate additional interventions to alleviate CIN

A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. EXPERIMENTAL DESIGN: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. RESULTS: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. CONCLUSIONS: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy