Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

Apolipoprotein E genotype and Cognition in Bipolar Disorder

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer`s Disease (AD). APOE allele *3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well-established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18-35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele *2 presented better cognitive performance. The presence of allele *4 was associated with worse performance in a few executive tasks. APOE *3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Background/Aims: Prolactin (PRL) secretion and its gene expression are inhibited by dopamine. Prolactinomas are the most common secreting pituitary adenomas, and dopamine agonists (DA) are the first choice for their treatment. However, a subset of patients is resistant to DA. As the mechanisms involved in DA resistance are not fully understood, the aim of this study was to obtain new insights regarding the molecular differences between the prolactinomas that are responsive to DA and those that are resistant. Methods: Tumor tissue samples were collected from 17 patients who harbored prolactinomas, which were classified as responsive or resistant according to their clinical and laboratorial reaction to DA. The expression of 6 genes was evaluated by real-time polymerase chain reaction: dopamine receptor type 2 (DRD 2), nerve growth factor-beta (NGFB) and its receptor (NGFR), estrogen receptor-alpha (ERA), estrogen receptor-beta (ERB) and the pituitary tumor transforming gene (PTTG). Results: Median DRD 2 and NGFR expression in responsive patients was significantly higher than in resistant ones (p = 0.029 and p = 0.020, respectively). Moreover, the expressions of DRD 2 and NGFR were positively correlated with PRL decrease during treatment (r = 0.66, p = 0.005 and r = 0.57, p = 0.044, respectively). Furthermore, ERB expression was positively correlated to PTTG expression (r = 0.68, p = 0.032) and negatively correlated to NGFB expression (r = -0.75, p = 0.02). Conclusions: DRD2 and NGFR expressions are related to the responsiveness of prolactinoma to DA. However, PTTG, ERB and ERA expressions are not. Also ERB, ERA and PTTG expressions did not present a clear correlation to tumor aggressiveness. Furthermore, the response of prolactinomas to DA should be viewed as a spectrum ranging from the most responsive to the most resistant ones. Copyright (c) 2008 S. Karger AG, Basel

Obesity, estrone, and coronary artery disease in postmenopausal women

Objectives: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. Methods: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at I and 2 years. Women were grouped according to their BMI (kg/m(2)) as normal (18.5 <= BMI < 25), overweight (25 <= BMI < 30) or obese (BMI >= 30), and by low and high estrone levels (< 15 and >= 15 pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. Results: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p = 0.074) of greater all cause mortality in women with low estrone levels (< 15 mL). In this model, adjusted for BMI, age [OR 1.08; p = 0.03], C-reactive protein [OR = 1.24; p = 0.024] and hypertension [OR = 6.22; p = 0.003] were independent predictors of all cause mortality. Conclusions: Postmenopausal women with low estrone levels (< 15 pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients

The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3`A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p = 0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome. (C) 2011 Elsevier Ltd. All rights reserved.

Parathyroid hormone secretion in women in late menopause submitted to EDTA-induced hypocalcemia

Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in Young women (Group Y = 30.9 years, N = 7) and in women in late menopause (Group M = 64.7 years, N = 7) and their relationship to bone mineral density. Methods: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2 h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine Lis well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). Results: The aged patients presented lower femoral BMD (Y = 0.860 g/cm(2) vs. M = 0.690 g/cm(2), P < 0.01), With four of them having a T score lower than - 2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak = 236 pg/ml) than for subjects with osteoporosis (OM: peak = 134.4 pg/ml). Conclusions: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Assessment of Vascular Effects of Tamoxifen and Its Metabolites on the Rat Perfused Hindquarter Vascular Bed

Tamoxifen has been suggested to produce beneficial cardiovascular effects, although the mechanisms for these effects are not fully known. Moreover, although tamoxifen metabolites may exhibit 30-100 times higher potency than the parent drug, no previous study has compared the effects produced by tamoxifen and its metabolites on vascular function. Here, we assessed the vascular responses to acetylcholine and sodium nitroprusside on perfused hindquarter vascular bed of rats treated with tamoxifen or its main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen, and endoxifen) for 2 weeks. Plasma and whole-blood thiobarbituric acid reactive substances (TBARS) concentrations were determined using a fluorometric method. Plasma nitrite and NOx (nitrite + nitrate) concentrations were determined using an ozone-based chemiluminescence assay and Griess reaction, respectively. Treatment with tamoxifen reduced the responses to acetylcholine (pD(2) = 2.2 +/- 0.06 and 1.9 +/- 0.05 after vehicle and tamoxifen, respectively; P < 0.05), while its metabolites improved these responses (pD(2) = 2.5 +/- 0.04 after N-desmethyl-tamoxifen, 2.5 +/- 0.03 after 4-hydroxy-tamoxifen, and 2.6 +/- 0.08 after endoxifen; P < 0.01). Tamoxifen and its metabolites showed no effect on endothelial-independent responses to sodium nitroprusside (P > 0.05). While tamoxifen treatment resulted in significantly higher plasma and whole blood lipid peroxide levels (37% and 62%, respectively; both P < 0.05), its metabolites significantly decreased lipid peroxide levels (by approximately 50%; P < 0.05). While treatment with tamoxifen decreased the concentrations of markers of nitric oxide formation by approximately 50% (P < 0.05), tamoxifen metabolites had no effect on these parameters (P > 0.05). These results suggest that while tamoxifen produces detrimental effects, its metabolites produce counteracting beneficial effects on the vascular system and on nitric oxide/reactive oxygen species formation.

Oestradiol Potentiates Hormone Secretion and Neuronal Activation in Response to Hypertonic Extracellular Volume Expansion in Ovariectomised Rats

Secretion of vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) is an essential mechanism for the maintenance of hydromineral homeostasis. Secretion of these hormones is modulated by several circulating factors, including oestradiol. However, it remains unclear how oestradiol exerts this modulation. In the present study we investigated the participation of oestradiol in the secretion of VP, OT and ANP and in activation of vasopressinergic and oxytocinergic neurones of the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus in response to extracellular volume expansion (EVE). For this purpose, ovariectomised (OVX) rats treated for 7 days with vehicle (corn oil, 0.1 ml/rat, OVX+O group) or oestradiol (oestradiol cypionate, 10 mu g/kg, OVX+E group) were subjected to either isotonic (0.15 m NaCl, 2 ml/100 g b.w., i.v.) or hypertonic (0.30 m NaCl, 2 ml/100 g b.w., i.v.) EVE. Blood samples were collected for plasma VP, OT and ANP determination. Another group of rats was subjected to cerebral perfusion, and brain sections were processed for c-Fos-VP and c-Fos-OT double-labelling immunohistochemistry. In OVX+O rats, we observed that both isotonic and hypertonic EVE increased plasma OT and ANP concentrations, although no changes were observed in VP secretion. Oestradiol replacement did not alter hormonal secretion in response to isotonic EVE, but it increased VP secretion and potentiated plasma OT and ANP concentrations in response to hypertonic EVE. Immunohistochemical data showed that, in the OVX+O group, hypertonic EVE increased the number of c-Fos-OT and c-Fos-VP double-labelled neurones in the PVN and SON. Oestradiol replacement did not alter neuronal activation in response to isotonic EVE, but it potentiated vasopressinergic and oxytocinergic neuronal activation in the medial magnocellular PVN (PaMM) and SON. Taken together, these results suggest that oestradiol increases the responsiveness of vasopressinergic and oxytocinergic magnocellular neurones in the PVN and SON in response to osmotic stimulation.

Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats

Successful reproduction requires that changes in plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oxytocin (OT), estrogen (E-2) and progesterone (P-4) occur together with the display of maternal behaviors. Ovarian steroids and environmental stimuli can affect the dendritic spines in the rat hippocampus. Here, studying Wistar rats, it is described: (a) the sequential and concomitant changes in the hormonal profile of females at postpartum days (PP) 4, 8, 12, 16, 20 and 24, comparing to estrous cycle referential values; (b) the dendritic spine density in the stratum radiatum of CA1 (CA1-SR) Golgi-impregnated neurons in virgin females across the estrous cycle and in multiparous age-matched ones; and (c) the proportion of different types of spines in the CAI-SR of virgin and postpartum females, both in diestrus. Plasma levels of gonadotrophins and ovarian hormones remained low along PP while LH increased and PRL decreased near the end of the lactating period. The lowest dendritic spine density was found in virgin females in estrus when compared to diestrus and proestrus phases or to postpartum females in diestrus (p < 0.03). Other comparisons among groups were not statistically significant (p > 0.4). There were no differences in the proportions of the different spine types in nulliparous and postpartum females (p > 0.2). Results suggest that medium layer CA1-SR spines undergo rapid modifications in Wistar females across the estrous cycle (not quite comparable to Sprague-Dawley data or to hormonal substitutive therapy following ovariectomy), but persistent effects of motherhood on dendritic spine density and morphology were not found in this area. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures

Study objective: To compare the effects of ethinylestradiol (EE) and 17 beta-estradiol (E(2)) on nitric oxide (NO) production and protection against oxidative stress in human endothelial cell cultures. Design: Experimental study. Settings: Research laboratory. Material: Human ECV304 endothelial cell cultures. Intervention(s): The NO synthesis was determined by flow cytometry, and oxidative stress was determined by a cell viability assay, after exposure to hydrogen peroxide (H(2)O(2)) and stimulation of endothelial cells with EE at concentrations similar to those of a contraceptive containing 30 mu g EE. Main Outcome Measure(s): The effects of EE were compared with those of E(2) at concentrations similar to those occurring during the follicular phase. Result(s): Ethinylestradiol did not increase NO synthesis and did not protect cells against oxidative stress. The viability of the cells incubated with E(2) in combination with H(2)O(2) was greater than the viability obtained with H(2)O(2) only or with H(2)O(2) in combination with EE. The cells stimulated with E(2) presented a significant increase in NO production compared with control. Conclusion(s): In contrast to the effects of E(2), EE did not protect human ECV304 endothelial cells against oxidative stress and did not increase their production of NO. (Fertil Steril (R) 2010; 94: 1578-82. (C) 2010 by American Society for Reproductive Medicine.)

Basal levels of DNA damage detected by micronuclei and comet assays in untreated breast cancer patients and healthy women

Breast cancer is the second most frequent type of cancer worldwide and is the most common malignant disease among women. Risk factors for breast cancer include early menarche, late menopause, hormonal therapies, exposure to environmental pollutants, smoking and alcohol use. However, increased or prolonged exposure to estrogen is the most important risk factor. It has been suggested that accumulation of DNA damage may contribute to breast carcinogenesis. Epidemiological studies suggest that cytogenetic biomarkers such as micronuclei in peripheral blood lymphocytes may predict cancer risk because they indicate genomic instability in target tissues. The objective of the present study was to evaluate the frequencies of micronuclei and the extent of DNA damage detected by comet assay in peripheral blood lymphocytes of untreated breast cancer patients and healthy women. The study was conducted using peripheral blood lymphocytes from 45 women diagnosed for Ductal ""in situ"" or invasive breast carcinoma and 85 healthy control women. Micronuclei and comet assays were performed to detect spontaneous DNA damage. The results showed that micronuclei frequencies and tail intensity, detected by comet assay, were significantly higher in the breast cancer group than in controls. The levels of DNA damage were similar in smokers and non-smokers, and aging did not influence the frequencies of micronuclei or tail intensity values observed in either group. In conclusion, the present work demonstrates higher levels of DNA damage in untreated breast cancer patients than in healthy women.

Influence of third-generation oral contraceptives on the complexity analysis and symbolic dynamics of heart rate variability

Objective To evaluate the influence of oral contraceptives (OCs) containing 20 mu mu g ethinylestradiol (EE) and 150 mu mu g gestodene (GEST) on the autonomic modulation of heart rate (HR) in women. Methods One-hundred and fifty-five women aged 24 +/-+/- 2 years were divided into four groups according to their physical activity and the use or not of an OC: active-OC, active-non-OC (NOC), sedentary-OC, and sedentary-NOC. The heart rate was registered in real time based on the electrocardiogram signal for 15 minutes, in the supine-position. The heart rate variability (HRV) was analysed using Shannon`s entropy (SE), conditional entropy (complexity index [CInd] and normalised CInd [NCI]), and symbolic analysis (0V%, 1V%, 2LV%, and 2ULV%). For statistical analysis the Kruskal-Wallis test with Dunn post hoc and the Wilcoxon test (p < 0.05 was considered significant) were applied. Results Treatment with this COC caused no significant changes in SE, CInd, NCI, or symbolic analysis in either active or sedentary groups. Active groups presented higher values for SE and 2ULV%, and lower values for 0V% when compared to sedentary groups (p < 0.05). Conclusion HRV patterns differed depending on life style; the non-linear method applied was highly reliable for identifying these changes. The use of OCs containing 20 mu mu g EE and 150 mu mu g GEST does not influence HR autonomic modulation.

Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue

Background: The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-TUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. Study Design: This was a randomized, prospective, open clinical Study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion., and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interlelikin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. Results: After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean +/- SD) of VCAM (92.8 +/- 4.2 to 91.2 +/- 2.7 ng/mL, p=.04), CRP (0.38 +/- 0.30 to 0.28 +/- 0.21 mg/dL, p=.03), total cholesterol (247.0 +/- 85.0 to 180.0 +/- 31.0 mg/dL, p=.0002), triglycerides (118.0 +/- 76.0 to 86.5 +/- 41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5 +/- 66.0 to 114.5 +/- 25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0 +/- 20.5 to 48.5 +/- 10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5 +/- 2.9 to 13.0 +/- 2.7 mu mol/L, p=.04) and a reduction in IL-6 levels (4.3 +/- 3.9 to 2.3 +/- 0.8 pg/mL, p=.005), VCAM (94.0 +/- 3.8 to 92.0 +/- 1.6 ng/mL, p=.03) and total leukocytes (7330 +/- 2554 to 6350 +/- 1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. Conclusions: This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-TUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment. (C) 2010 Elsevier Inc. All rights reserved.

Tibolone in postmenopausal women with systemic lupus erythematosus: A pilot study

Objective: To determine the influence of the use of tibolone on the frequency of flares of systemic lupus erythematosus (SLE) in postmenopausal patients. Methods: Thirty patients with inactive or controlled SLE were included in the study. Patients were randomized to receive a 12-month course of either tibolona (2.5 mg/day) or placebo. The following were investigated: hypoestrogenism symptoms by Kupperman index, weight; anti-dsDNA antibodies; SLE flares (frequency) assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and biochemical profile (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, complement components [C3/C4], alpha 1-acid glycoprotein, urea, creatinine, 24-h proteinuria, C-reactive protein and erythrocyte sedimentation rate). Results: The reduction in Kupperman index was greater in the patients using tibolone than in those using placebo. I-lie mean SLEDAI was not different between the groups during the study as well as SLE flare frequency (tibolone: 2/15 [13.3%] vs. placebo: 1/15 [6.7%]; p = 0.54). All cases of flares were considered mild to moderate. Although the groups were similar at the baseline evaluation, after 6 and 12 months of treatment lower values were found in the tibolone group for triglycerides (6 months: 161.6 +/- 30.9 mg/dl vs. 194.4 +/- 46.5: p = 0.04: 12 months 163.7 +/- 29.8 mg/dl vs. 204.1 +/- 49.9 mg/dl; p = 0.02: tibolone vs. placebo group, respectively) and for HDL-C (6 months: 40.7 +/- 10.7 mg/dl vs. 53.4 +/- 16.5; p = 0.02; 12 months: 47.2 +/- 7.9 mg/dl vs. 63.2 +/- 16.3 mg/dl; p < 0.01: tibolone vs. placebo group, respectively). There were no differences between the two groups in any of the remaining variables. Conclusion: In patients with inactive or stable SLE, the short-term use of tibolone did not significantly affect the frequency of flares. In addition, tibolone was well tolerated and effective to control hypoestrogenism related symptoms in SLE patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

Objectives: Studies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg). Methods: A total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (IMT) and stiffness index (beta); blood total cholesterol, HDL and triglycerides were assessed. Results: All three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 +/- 36.31 mg/dL vs. 250.59 +/- 38.37 mg/dL vs. 245.09 +/- 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01-ANOVA), the highest triglycerides (139.34 +/- 41.82 mg/dL vs. 111.35 +/- 28.22 mg/dL vs.122.09 +/- 33.42 mg/dL; p < 0.01), the highest FMD (6.32 +/- 2.33% vs. 4.10 +/- 2.06% vs. 4.66 +/- 2.52%; p < 0.01) and the lowest stiffness index (beta) (5.08 +/- 1.68 vs. 6.28 +/- 1.75 vs. 5.99 +/- 1.86; p=0.01). LTZg did not differ significantly from NETg on any evaluated parameter. Conclusions: We did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (beta) and FMD between women receiving tamoxifen anti letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole. (C) 2008 Elsevier Ireland Ltd. All rights reserved.