Hot flashes are associated with CYP2D6 genotype in breast cancer survivors taking tamoxifen.

摘要: CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #6045 Background: We have previously shown that participants in the Women's Healthy Eating and Living (WHEL) study comparison group who reported hot flashes after breast cancer treatment had more favorable disease-free survival than women did not report flashes. However, this was case intervention group. The polymorphic CYP450 enzyme CYP2D6 catalyzes conversion of tamoxifen (TAM) to one its key active metabolites, endoxifen. Some studies suggested certain genetic variants are associated with a decreased likelihood flashes, reduced endoxifen levels an increased risk disease recurrence receiving adjuvant TAM therapy. This analysis performed estimate association between genotype early stage survivors took WHEL study. Methods: randomized trial dietary survivors, enrolled within 4 years diagnosis from 1995-2000. Participants self-reported use, flash severity menopausal status at entry. Clinical characteristics (tumor stage, estrogen receptor status, chemotherapy) were extracted medical records. Blood samples obtained by venipuncture, separated stored -80 deg. DNA buffy coat analyzed using Roche AmpliChip Test. Women classified according their predicted phenotype as Extensive (EM), Heterozygous (Het EM), Intermediate (IM), Poor (PM), or Ultrarapid (UM) Metabolizers. Results: Overall, 1434 verified receptor-positive I II cancers taking baseline for least months. A total 1411 successfully genotyped phenotypes follows: 468 EM (33.2%); 665 Het EM(47.1%), 164 IM (11.6%), 86 PM (6.1%) 28 UM (2.0%). In univariate analyses, there significant difference among relation baseline: 79.8% EMs, 76.3% 80.1% IMs, 63.9% PMs, 75% UMs (χ2= 11.3, p=0.02). After controlling age, time since diagnosis, half likely referent (OR= 0.46; 95% CI= 0.28-0.78; p=0.003). Additional analyses serum associations outcome underway. Conclusion: study, Metabolizers TAM, based on genotype, experiencing while cancer. Citation Information: Res 2009;69(2 Suppl):Abstract nr 6045.