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CYP2D6 predicted treatment outcome in tamoxifen-treated metastatic breast cancer
International Conference on Molecular Targets and Cancer Therapeutics
Inherited variation of the gene CYP2D6 had a negative impact on OS in patients treated with tamoxifen for hormone receptor-positive metastatic breast cancer, according to the results of a study presented by Laureen A. Lammers, PharmD, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
“Our study found that, for women with hormone receptor-positive metastatic breast cancer, CYP2D6 phenotype, as derived from both genotype information and co-medication use, is an important predictor of treatment outcomes associated with tamoxifen,” said Lammers, from the Erasmus Medical Center in Rotterdam, the Netherlands. “In addition, our study confirms that concomitant use of drugs that inhibit CYP2D6 limit the effectiveness of tamoxifen therapy, and should, therefore, be discouraged.”
CYP2D6 plays an important role in the metabolism of tamoxifen into the active metabolite endoxifen; however, variations in the gene or use of CYP2D6 inhibiting medications reduce endoxifen concentrations in patients being treated for breast cancer, according to background information.
In this study, Lammers and colleagues sought to examine the effect of the CYP2D6 predicted phenotype — the combined effect of genetic variants and concomitant use of CYP2D6 inhibiting medication — on patients' outcomes, specifically OS in women being treated with tamoxifen.
The researchers examined patients being treated with tamoxifen for hormone receptor-positive breast cancer who had blood samples available.
They found that patients with predicted poor metabolizer phenotypes had a worse OS compared with extensive metabolizers (HR=2.11; P=.031). Those patients with intermediate and extensive metabolizer phenotype had comparable time to progression and OS and were later examined as one group by researchers.
Patients with poor metabolizer phenotypes had a shorter time to progression compared with the intermediate/extensive metabolizer patients (1.7 years vs. 2.9 years; P=.09). In addition, poor metabolizers had a significantly shorter OS than intermediate/extensive metabolizers (5.4 years vs. 9.9 years; P=.01).
The researchers also found that the concomitant use of CYP2D6 inhibitors was independently associated with a worse OS (HR=3.55) and worse time to progression (HR=2.97) compared with patients not receiving the drugs.
For more information:
- Lammers L. #C118. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Nov. 15-19, 2009; Boston.