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.
More In the Journals summaries>>