Abstract
IntroductionNot all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change.MethodsBaseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted comparing subjects who experienced >10% reduction in PMD to those who experienced ≤10% reduction or increase.ResultsAfter multivariate adjustment, PMD change was found to be significantly associated with the degree of CYP2D6 enzyme functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95% confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to experience a >10% reduction, respectively.ConclusionsTamoxifen-induced change in PMD appears to have a genetic component.
Highlights
Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition
The Wald test was used to determine the statistical significance of an overall linear trend for the association between Cytochrome P450 2D6 (CYP2D6) metabolizer status, treated as a semi-continuous variable, and binary percent mammographic density (PMD) change (P trend)
Odds ratios (ORs) and 95% confidence intervals (CIs) (lower bound of a 95% confidence interval (L95), upper bound of a 95% confidence interval (U95)) were estimated by applying a logistic regression model, using the group with 10% reduction as a reference
Summary
Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change. Tamoxifen reduces both the risk and recurrence of breast cancer [1,2]. There may be genetic reasons as to why some women experience a decrease in mammographic density and a dramatic influence on risk and prognosis of breast cancer. We hypothesize that only women who are able to metabolize tamoxifen would experience a decrease in density and a potential parallel effect on breast cancer risk and prognosis.
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