2/1/10
Personalized Cancer Care Off to Slow Start (Questions Tamoxifen CYP2D6 testing)
http://www.gooznews.com/node/3250
Quote:
With the cost of new cancer drugs soaring to $10,000 a month or more, genomic analyses of cancer tumors hold out the hope that oncologists will be able to identify in advance which patients will benefit from use of pricey new drugs. A new
draft report from the Agency for Healthcare Research and Quality suggests that day is still a ways off.
In the finding most likely to cause controversy, the AHRQ report found there was "no consistent associations" between breast cancer patients with the relevant CYP2D6 polymorphism and the outcome of tamoxifen therapy, whether as primary treatment or in as post-operative adjuvant therapy. Estimates vary, but anywhere from 10 to 40 percent of women have the gene variant of
CYP2D6 that is believed to slow the metabolism of tamoxifen and make it less effective. A number of companies sell a $300 test that can show if women have the allegedly telltale
CYP2D6 polymorphism.
As is often the case, the 13 studies identified by the systematic review didn't contain enough data to draw definitive conclusions. "Most studies were relatively small and thus underpowered to detect what would be a plausible effect size for the modification of response to tamoxifen by a single polymorphism," the report noted.
and then, same day....a new Tamoxifen marker:
LINK
Discovery could aid cancer care
(UKPA) – 6 hours ago
A new gene discovery could lead to more personalised treatment for breast cancer patients, scientists announced.
Experts have identified a gene, FKBPL, which predicts how women will respond to the commonly used drug tamoxifen.
The medicine interferes with the activity of the female hormone oestrogen, and is suitable for women with hormone sensitive breast cancer.
About 28,000 women in the UK are diagnosed with this type of cancer each year and thousands are given tamoxifen for five years after an initial round of treatment or surgery.
However, not all women respond to the drug and it is estimated that only around two-thirds actually benefit.
Now, scientists at Queen's University Belfast have found that high levels of FKBPL in breast cancer cells suggest a woman will respond well to tamoxifen and have a better chance of survival than women with low levels of the gene.
Tracy Robson and Hayley McKeen published the study, funded by the charity Breast Cancer Campaign, in the journal Cancer Research.
Dr Robson said: "I believe that many women are being treated with tamoxifen without knowing whether it will benefit them.
"This research is a step in the right direction towards personalised treatment, ensuring that appropriate therapies are given right at the point of diagnosis, avoiding unnecessary treatment.
"More importantly this research should allow us to identify which patients are unlikely to respond to or eventually relapse on tamoxifen therapy, which means they could be treated more aggressively with chemotherapy."
Same month:
J Clin Oncol. 2010 Feb 1. [Epub ahead of print]
Significant Effect of Polymorphisms in CYP2D6 and ABCC2 on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Breast Cancer Patients.
Kiyotani K,
Mushiroda T,
Imamura CK,
Hosono N,
Tsunoda T,
Kubo M,
Tanigawara Y,
Flockhart DA,
Desta Z,
Skaar TC,
Aki F,
Hirata K,
Takatsuka Y,
Okazaki M,
Ohsumi S,
Yamakawa T,
Sasa M,
Nakamura Y,
Zembutsu H.
Laboratories for Pharmacogenetics, Genotyping Development, and Medical Informatics, RIKEN Center for Genomic Medicine, Yokohama; Department of Clinical Pharmacokinetics and Pharmacodynamics, School of Medicine, Keio University; Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo; Department of Surgery, Itoh Surgery and Breast Clinic; Department of Surgery, Yamakawa Breast Clinic, Kochi; First Department of Surgery, Sapporo Medical University; Department of Surgery, Sapporo Breast Surgical Clinic, Sapporo; Department of Breast Surgery, Kansai Rosai Hospotal, Hyogo; Department of Breast Oncology, Shikoku Cancer Center, Ehime; Department of Surgery, Tokushima Breast Care Clinic, Tokushima, Japan; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
PURPOSE: The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. PATIENTS AND METHODS: We studied 282 patients with hormone receptor-positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d. RESULTS: CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with