Patients who are homozygous for polymorphisms in the CYP2D6 gene that cause a loss of or greatly reduced protein function are called Poor Metabolizers (PMs). They either do not produce active tamoxifen metabolites or produce them at a very low level.
Recent data on fewer than 300 patients have shown that these patients have a worse outcome when treated with tamoxifen compared with patients who do not have functional polymorphisms in the CYP2D6 gene. Because postmenopausal women with hormone-positive breast cancer can choose between taking an aromatase inhibitor (AI) for 5 years or taking tamoxifen for 2-3 years followed by an AI for their endocrine therapy, knowing a woman's CYP2D6 genotype would provide valuable information to help guide treatment.
Postmenopausal women who are PMs should avoid tamoxifen as the current, yet limited data support the lack of efficacy of tamoxifen in PMs.
References:
Knox et al., Cytochrome p450 2D6 status predicts breast cancer relapse in women receiving adjuvant tamxifen. Proceedings of The American Society of Clinical Oncology, 2006.
Goetz et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005 Dec 20; 23(36):9312-8.