Browsing by Author "Nguyen, Anne"

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    Composite Functional Genetic and Comedication CYP2D6 Activity Score in Predicting Tamoxifen Drug Exposure Among Breast Cancer Patients
    (Wiley, 2010-04) Borges, Silvana; Desta, Zeruesenay; Jin, Yan; Faouzi, Azzouz; Robarge, Jason D.; Philip, Santosh; Nguyen, Anne; Stearns, Vered; Hayes, Daniel; Rae, James M.; Skaar, Todd C.; Flockhart, David A.; Li, Lang
    Accurate assessment of CYP2D6 phenotypes from genotype is inadequate in patients taking CYP2D6 substrate together with CYP2D6 inhibitors. A novel CYP2D6 scoring system is proposed that incorporates the impact of concomitant medications with the genotype in calculating the CYP2D6 activity score. Training (n = 159) and validation (n = 81) data sets were obtained from a prospective cohort tamoxifen pharmacogenetics registry. Two inhibitor factors were defined: 1 genotype independent and 1 genotype based. Three CYP2D6 gene scoring systems, and their combination with the inhibitor factors, were compared. These 3 scores were based on Zineh, Zanger, and Gaedigk's approaches. Endoxifen/NDM-Tam plasma ratio was used as the phenotype. The overall performance of the 3 gene scoring systems without consideration of CYP2D6-inhibiting medications in predicting CYP2D6 phenotype was poor in both the training set (R(2) = 0.24, 0.22, and 0.18) and the validation set (R(2) = 0.30, 0.24, and 0.15). Once the CYP2D6 genotype-independent inhibitor factor was integrated into the score calculation, the R(2) values in the training and validation data sets were nearly twice as high as the genotype-only scoring model: (0.44, 0.43, 0.38) and (0.53, 0.50, 0.41), respectively. The integration of the inhibitory effect of concomitant medications with the CYP2D6 genotype into the composite CYP2D6 activity score doubled the ability to predict the CYP2D6 phenotype. However, endoxifen phenotypes still varied substantially, even with incorporation of CYD2D6 genotype and inhibiting factors, suggesting that other, as yet unidentified factors must be involved in tamoxifen activation.
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    Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy.
    (ASCO, 2008-12-20) Jin, Yan; Hayes, Daniel F.; Li, Lang; Robarge, Jason D.; Skaar, Todd C.; Philips, Santosh; Nguyen, Anne; Schott, Anne; Hayden, Jill; Lemler, Suzanne; Storniolo, Anna Maria; Flockhart, David A.; Stearns, Vered
    PURPOSE: Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) alpha and beta (ESR1 and ESR2, respectively) are associated with tamoxifen-induced hot flashes. PATIENTS AND METHODS: We determined ESR1 PvuII and XbaI and ESR2-02 genotypes in 297 women who were initiating tamoxifen. One-week hot flash diaries were collected to calculate a hot flash score (frequency x severity) before and 1, 4, 8, and 12 months after starting tamoxifen. RESULTS: Approximately 80% of 297 participants reported hot flashes before or during the first year of tamoxifen. After 4 months of tamoxifen, premenopausal women who did not receive adjuvant chemotherapy had a four-fold increase in hot flash score (from 5.9 to 23.6; P = .003) compared with a 1.17-fold increase (from 19.6 to 23; P = .34) in those who received chemotherapy. In premenopausal women, increased number of ESR1 PvuII and XbaI CG alleles was associated with higher baseline hot flash scores compared with those who had other haplotypes (P = .0026). At 4 months, postmenopausal women with ESR1 PvuII CC and ESR2-02 GG genotypes had 4.6 times increases in hot flash scores than other postmenopausal women (56 v 12; P = .0007). Women who had the ESR2-02 AA genotype were significantly less likely to experience tamoxifen-induced hot flashes than women who carried at least one ESR-02 G allele (hazard ratio, 0.26; 95% CI, 0.10 to 0.63; P = .001). CONCLUSION: Knowledge of menopausal status, prior chemotherapy, and ESR genotype may help predict which women are most likely to suffer hot flashes during tamoxifen treatment.
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    IMPRS Research Symposium Program
    (Indiana University School of Medicine, 2024) Nguyen, Anne; Herbert, Brittney-Shea
    Program includes the names of symposium presenters, titles of their research projects, and the names and departmental affiliations of their mentors.
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    Indiana Biobank (IB)
    (Office of the Vice Chancellor for Research, 2011-04-08) Nguyen, Anne; Shekhar, Anantha; Flockhart, David
    The Indiana Biobank (IB) was established in July 2010 as a conduit in the new era of personalized medicine to serve the needs of the Indiana research communities and to make an impact on Hoosier health. The overall objective of the Indiana Biobank is to create a collection of high quality biospecimens that are well annotated and linked to the electronic health record, genomic and proteomic data, to provide to the research community to carry out translational research. The ability to successfully do research and translate to the clinical setting is greatly facilitated by the availability of an extensive biorepository of biological samples, with accompanying clinical and genomic data, procured from patients at IU Health, Wishard and other clinical venues throughout Indiana.