Pii‐21

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109873/1/cptclpt2006159.pd

Pi‐29

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110026/1/cptclpt200664.pd

Pii‐18

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110052/1/cptclpt2006156.pd

Plasma Letrozole Concentrations in Postmenopausal Women With Breast Cancer Are Associated With CYP2A6 Genetic Variants, Body Mass Index, and Age

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109858/1/cptclpt2011174.pd

Evolución del comportamiento físico químico de los pozos en Termas de Rio Hondo como aporte al diagnóstico de situación actual

En la Provincia de Santiago del Estero, la Ciudad de Termas de Rio Hondo constituye un importante ce ntro urbano turístico invernal. Posee en el subsuelo, aguas termales usadas en balneoterapia con propiedades termomedicinales. La extracción excesiva en época de temporada invernal asociadas al turismo, genera un desfasaje entre las demandas potenciales y la disponibilidad del recurso, alterando el sistema. La geoquímica, provee información sobre la distribución de los elementos químicos y su evolución espacial y temporal en el sistema hídrico, caracterizando el agua de los acuíferos y definiendo problemas ambientales. La metodología, se basó en la selección de resultados de análisis físico-químicos existentes y actuales comparados, respecto a TSD. Las anomalías observadas en la concentración de los iones, respecto a las profundidades de explotación están asociadas a la presión antrópica del sistema.In the province of Santiago del Estero, the City of Termas de Rio Hondo is a major urban center winter resort. It has in the subsurface thermal properties used in balneotherapy termomedicinales. Excessive extraction in times of winter season associated with tourism, generates a potential mismatch between the demands and resource availability, altering the system. The geochemistry, provides information on the distribution of chemical elements and their spatial and temporal evolution in the water system, characterizing water aquifers and defining environmental problems. The methodology was based on the selection of results of physicochemical analysis of existing and current compared with respect to TSD. The anomalies observed in the concentration of ions, with respect to depths of operation are associated with human pressure system.Universidad Nacional de La Plat

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Background: Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy. Methods: Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment. Results: Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed. Conclusion: Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes

Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients

The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a ‘score’ based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r2=0.935, P=0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely

Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy.

BACKGROUND: Tamoxifen, a selective oestrogen receptor (ER) modulator, increases bone mineral density (BMD) in postmenopausal women and decreases BMD in premenopausal women. We hypothesised that inherited variants in candidate genes involved in oestrogen signalling and tamoxifen metabolism might be associated with tamoxifen effects in bone. METHODS: A total of 297 women who were initiating tamoxifen therapy were enrolled in a prospective multicentre clinical trial. Lumbar spine and total hip BMD values were measured using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of tamoxifen therapy. Single-nucleotide polymorphisms (SNPs) in ESR1, ESR2, and CYP2D6 were tested for associations in the context of menopausal status and previous chemotherapy, with a mean percentage change in BMD over 12 months. RESULTS: The percentage increase in BMD was greater in postmenopausal women and in those patients who had been treated with chemotherapy. No significant associations between tested SNPs and either baseline BMD or change in BMD with 1 year of tamoxifen therapy were detected. CONCLUSION: The evaluated SNPs in ESR and CYP2D6 do not seem to influence BMD in tamoxifen-treated subjects