A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole.

BACKGROUND: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. METHODS: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. RESULTS: Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). CONCLUSIONS: Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.

The peripheral arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population.

BACKGROUND: The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population. METHODS: We performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease. RESULTS: The prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); p < 0.001).Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index > or =25 Kg/m2 OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors. CONCLUSIONS: The prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.

Does heart failure therapy differ according to patient sex?

OBJECTIVES: To assess differences in clinical characteristics, treatment and outcome between men and women with heart failure (HF) treated at a multidisciplinary HF unit. All patients had their first unit visit between August 2001 and April 2004. PATIENTS: We studied 350 patients, 256 men, with a mean age of 65 +/- 10.6 years. In order to assess the pharmacological intervention more homogeneously, the analysis was made at one year of follow-up. RESULTS: Women were significantly older than men (69 +/- 8.8 years vs. 63.6 +/- 10.9 years, p < 0.001). Significant differences were found in the HF etiology and in co-morbidities. A higher proportion of men were treated with ACEI (83% vs. 68%, p < 0.001) while more women received ARB (18% vs. 8%, p = 0.006), resulting in a similar percentage of patients receiving either of these two drugs (men 91% vs. women 87%). No significant differences were observed in the percentage of patients receiving beta-blockers, loop diuretics, spironolactone, anticoagulants, amiodarone, nitrates or statins. More women received digoxin (39% vs. 22%, p = 0.001) and more men aspirin (41% vs. 31%, p = 0.004). Carvedilol doses were higher in men (29.4 +/- 18.6 vs. 23.8 +/- 16.4, p = 0.03), ACEI doses were similar between sexes, and furosemide doses were higher in women (66 mg +/- 26.2 vs. 56 mg +/- 26.2, p < 0.05). Mortality at 1 year after treatment analysis was similar between sexes (10.4% men vs. 10.5% women). CONCLUSIONS: Despite significant differences in age, etiology and co-morbidities, differences in treatment between men and women treated at a multidisciplinary HF unit were small. Mortality at 1 year after treatment analysis was similar for both sexes.

Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality.

BACKGROUND: The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). METHODS/DESIGN: This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. DISCUSSION: In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of arterial disease than the classical cardiovascular risk factors and may, therefore, contribute to improving the predictive value of the equations of cardiovascular risk and thereby allowing optimisation of multifactorial treatment of atherosclerotic disease.

En el camino hacia la excelencia científical / On the road to scientific excellence

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Senología y patología mamaria en personas trans / Senology and breast disease in trans-gender

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Cuantificando la excelencia / Quantifying excellence

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Value of the identification of microsatellite instability in colorectal cancer.

OBJECTIVE: Recent studies defend a possible prognostic and therapeutic value of the identification of microsatellite instability (MSI) in colorectal cancer. This work tries to assess the impact that the identification of MSI tumours can have in clinical practice. MATERIAL AND METHODS: We recovered tumour samples from 92 of the 143 patients operated on for colorectal cancer in our institution between 1995 and 2000. Five MSI markers (BAT 25, BAT 26, D2S123, D5S346 and D17S250) were studied on them. The rate and clinicopathologic characteristics of MSI tumours were investigated along with their impact on the global and disease-free survival as compared with microsatellite stable (MSS) tumours. RESULTS: All 5 microsatellite markers' status were established in 73 patients (79.3% of the samples). Among them, 7 tumours showed instability in just one marker (low microsatellite instability [MSI-L]) whereas 5 tumours had mutations in 2 or more markers (high microsatellite instability [MSI-H]), for a total 15.4% rate of MSI tumours. All MSI-H tumours were located in the right colon. We could not fi nd any impact from MSI detection on global or disease-free survival. CONCLUSIONS: MSI determination did not identify groups of patients with a different prognosis. Moreover, with such low incidence its determination can only be justified in those cases that fulfill Bethesda's criteria to identify families with Lynch's syndrome.