Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen

Goetz, Matthew P.; Suman, Vera J.

doi:10.1002/cncr.24827

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…The relationship between breast cancer and the CYP gene family was recently reported, including CYP1B1 (Economopoulos and Sergentanis, 2010;Ozbek et al, 2010), CYP2J2 (Jiang et al, 2007(Jiang et al, , 2009), CYP2D6 (Stingl et al, 2010;González-Tejera et al, 2010;Thompson et al, 2011), CYP2C8 (Knüpfer et al, 2004;Dixit, et al, 2007;Jernström et al, 2009), CYP2C9 (Ekhart et al, 2008;Jernström et al, 2009) and CYP2C19 (Justenhoven et al, 2009;Ruiter et al, 2010;Goetz and Suman, 2010). Several studies have reported different conclusions for the relationship with CYP2C19.…”

Section: Discussionmentioning

confidence: 99%

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Gan¹,

Wang²,

Cao³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which significantly promote proliferation of cancer cells in vitro and in vivo. We looked for a possible association between human CYP2C19*3 gene polymorphism and breast cancer in the Chinese Han population. In a Chinese Han case-control study of breast cancer patients (N = 600) and age-and gender-matched healthy controls (N = 600), we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in breast cancer patients than in control subjects (6.67 vs 3.00%; P = 0.003). The odds ratio for carriers of AG + AA genotype for breast cancer was 2.31 (95% confidence interval = 1.27-4.43). Among patients, estrogen receptor, tumor size, histologic grade, presence of primary lymphonode metastases, progesterone receptor positivity, and age at diagnosis were not found to be significantly associated with CYP2C19*3 genotypes (all P > 0.05). We conclude that the CYP2C19*3 gene polymorphism is associated with breast cancer risk in Chinese Han women.

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Section: Discussionmentioning

confidence: 99%

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Gan¹,

Wang²,

Cao³

et al. 2011

Genet. Mol. Res.

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Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide

Gjerde

Gandini

Guerrieri-Gonzaga

et al. 2012

Breast Cancer Res Treat

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Tamoxifen dosage is based on the one-dose-fits-all approach. The anticancer effect of tamoxifen is believed to be due to the metabolites, 4-hydroxytamoxifen (4OHtam), and 4-hydroxy-N-desmethyltamoxifen (4OHNDtam/endoxifen). These demethylated metabolites of tamoxifen have been associated with its side effects, whereas the effect mediated by tamoxifen-N-oxide (tamNox) is still poorly understood. Our objective was to improve the therapeutic index of tamoxifen by personalizing its dosage and maintaining serum tamoxifen metabolite concentrations within a target range. We examined the levels of tamoxifen, 4OHtam, 4OHNDtam, N-desmethyltamoxifen (NDtam), N-desdimethyltamoxifen (NDDtam), and tamNox in serum and in breast tumors specimens of 115 patients treated with 1, 5 or 20 mg/day of tamoxifen for 4 weeks before surgery in a randomized trial. Furthermore, the metabolism of tamNox in MCF-7 breast cancer cells was also studied. The concentrations of tamoxifen and its metabolites in tumor tissues were significantly correlated to their serum levels. Tumor tissue levels were 5–10 times higher than those measured in serum, with the exception of tamNox. In MCF-7 cells, tamNox was converted back to tamoxifen. In contrast to the tissue distribution of tamNox, the concentrations of 4OHtam and 4OHNDtam in tumor tissues corresponded to their serum levels. The results suggest that implementation of therapeutic drug monitoring may improve the therapeutic index of tamoxifen. Furthermore, the tissue distribution of tamNox deviated from that of the other tamoxifen metabolites.

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Clinical Trials in the Elderly

Irvin¹,

Muss²

2012

Management of Cancer in the Older Patient

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Genetic polymorphisms of CYP2D610 and CYP2C192, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen

Cited by 3 publications

References 5 publications

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide

Clinical Trials in the Elderly

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