Genetic enzyme CYP2D6 variation was associated with outcomes in breast cancer

The presence of functional CYP2D6 alleles was linked to better clinical outcomes, while the presence of nonfunctional or reduced-function alleles were linked to worse outcomes in women with early stage breast cancer.

Researchers retrospectively collected data from a German breast cancer cohort and prospectively collected data from the U.S. North Central Cancer Treatment Group trial. Analyses were performed on 1,325 women diagnosed with stage I to stage III breast cancer between 1986 and 2005 treated with adjuvant tamoxifen. The majority of participants were postmenopausal (95.4%). Median follow-up was 6.3 years.

Women were classified as having extensive metabolism, heterozygous extensive/intermediate metabolism or poor metabolism. The recurrence rates were highest among those with poor metabolism (29.0%), followed by those with heterozygous extensive/intermediate metabolism (20.9%) and those with extensive metabolism (14.9%).

Risk for recurrence was increased among women with poor metabolism (HR=1.90; 95% CI, 1.10-3.28) and women with heterozygous extensive/intermediate metabolism (HR=1.40; 95% CI, 1.04-1.90) compared with those with extensive metabolism.

Additionally, event-free survival was worse for those with decreased CYP2D6 activity compared with women with extensive metabolism; those with poor metabolism and heterozygous extensive/intermediate metabolism had an HR of 1.33 (95% CI, 1.06-1.68) for event-free survival. Disease-free survival was also worse (HR=1.29; 95% CI, 1.03-1.61). No difference was observed for OS.

“Since tamoxifen is standard of care for premenopausal women with estrogen receptor–positive breast cancer, and tamoxifen as well as aromatase inhibitors are valid treatment options for postmenopausal patients, our findings provide a powerful argument for refined endocrine treatment,” the researchers wrote.

Schroth W. JAMA. 2009;302:1429-1436.