Semana del 10al 17 de Octubre de 2006

Dr. Juan Enrique Blümel

Reuters. Health Information

NEW YORK (Reuters Health) Sept 29 - Treatment with raloxifene (Evista; Eli Lilly), which is indicated for the treatment and prevention of osteoporosis, curbs the risk of invasive breast cancer in postmenopausal women regardless of the presence or absence of risk factors for breast cancer, according to a new study. The protective effect is greater in women with a family history of breast cancer. These are the findings of subgroup analyses of 7,705 women in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial and 4,011 in the Continuing Outcomes Relevant to Evista (CORE) trial. Dr. Marc E. Lippman of the University of Michigan in Ann Arbor said: "The most important observation is that when we look at different groups of women who might be expected to have differing risks of breast cancer -- and conceivably differing protective effects of raloxifene -- we do not detect important differences in relative benefit of raloxifene in preventing breast cancer." Over the 8 years of the MORE and CORE trials, treatment of postmenopausal women with  Raloxifene was associated with a significant 66% decrease in the incidence of invasive breast cancer. In the present analyses, Dr. Lippman and colleagues assessed the effect of raloxifene on invasive breast cancer incidence by the predicted level of breast cancer risk (higher versus lower risk) using both MORE and CORE data. In the placebo arms, older age (65 years or older), higher estradiol level, and a family history of breast cancer correlated with increased breast cancer risk (p < 0.05), they report in the September 1 issue of Clinical Cancer Research. Treatment with raloxifene reduced the risk of breast cancer markedly in both women at lower and those at higher breast cancer risk. "Hazard ratio point estimates were 0.11 to 0.67, corresponding to a 33% to 89% reduction in breast cancer risk with raloxifene versus placebo," Dr. Lippman and colleagues report. As mentioned, raloxifene's effect was more pronounced in women with a family history of breast cancer, a finding seen in the MORE trial as well.

Osteoporos Int. 2006 Oct 13; [Epub ahead of print]

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

Schott AM, Ganne C, Hans D, Monnier G, Gauchoux R, Krieg MA, Delmas PD, Meunier PJ, Colin C.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1856-62

Chiarelli AM, Kirsh VA, Klar NS, Shumak R, Jong R, Fishell E, Yaffe MJ, Boyd NF.

Background: There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer. Methods: This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression. Results: A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; CI, 1.10-2.90) for women taking combined HRT. Conclusionss: information on mammographic density and HRT use should be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening.

Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1871-7

Abrahamson PE, Gammon MD, Lund MJ, Flagg EW, Porter PL, Stevens J, Swanson CA, Brinton LA, Eley JW, Coates RJ.

Among postmenopausal women, obesity is linked to increased risk of breast cancer and poorer subsequent survival. For premenopausal women, obesity may reduce incidence, but less is known about its effect on prognosis, particularly for abdominal obesity. This study investigated whether general or abdominal obesity at diagnosis influenced survival in a cohort of young women with breast cancer. A population-based follow-up study was conducted among 1,254 women ages 20 to 54 who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta or New Jersey. Women were interviewed within several months of diagnosis and asked about their weight and height at age 20 and in the year before diagnosis. Study personnel did anthropometric measures at the interview. With 8 to 10 years of follow-up, all-cause mortality status was determined using the National Death Index (n = 290 deaths). Increased mortality was observed for women who were obese [body mass index (BMI), >/=30] at the time of interview compared with women of ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48; 95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05-2.19). Strong associations with mortality were found for women who were obese at age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, >/=25) at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This study provides evidence that breast cancer survival is reduced among younger women with general or abdominal obesity.

Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1849-55

Racial/Ethnic differences in postmenopausal endogenous hormones: the multiethnic cohort study.

Setiawan VW, Haiman CA,Stanczyk FZ, Le Marchand L, Henderson BE.

University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90033.

Postmenopausal women with increased estrogens and lowered sex hormone-binding globulin (SHBG) concentrations are at increased risk of breast cancer. In the Multiethnic Cohort Study, the highest incidence rates of postmenopausal breast cancer were observed among Native Hawaiians followed by Japanese Americans, Whites, African Americans, and Latinas. Ethnic differences in endogenous sex hormone profiles may contribute to some of the variation in breast cancer incidence. Plasma concentrations of androstenedione, testosterone, estrone (E(1)), estradiol (E(2)), and SHBG were measured in 739 postmenopausal women from the Multiethnic Cohort Study (240 African Americans, 81 Native Hawaiians, 96 Japanese Americans, 231 Latinas, and 91 Whites). After adjusting for age, known breast cancer risk factors and lifestyle factors, the mean levels of testosterone, estrogen, and SHBG varied across populations (Ps </= 0.004). Across racial/ethnic groups, Native Hawaiians had the highest mean levels of androstenedione, testosterone, and estrogens and the lowest mean levels of SHBG. Compared with Whites, Native Hawaiians had higher androstenedione (+22%, P = 0.017), total testosterone (+26%, P = 0.013), bioavailable testosterone (+33%, P = 0.002), E(1) (>/=21%; P = 0.009), total E(2) (+26%, P = 0.001), bioavailable E(2) (+31%, P < 0.001), and lower SHBG (-12% P = 0.07) levels. Compared with Whites, Japanese Americans had higher E(2) (+15%, P = 0.036) and bioavailable E(2) (+18%, P = 0.024) levels. African Americans also had higher E(1) (+21%, P = 0.004), E(2) (+20%, P = 0.007), and bioavailable E(2) (+20%, P = 0.015) levels compared with Whites, whereas mean levels in Latinas were similar to those of Whites. Many of the differences in endogenous postmenopausal hormonal milieu across these five racial/ethnic groups are consistent with the known differences in breast cancer incidence across these populations.

Maturitas. 2006 Oct 9; [Epub ahead of print]

van de Weijer PH, Mattsson LA, Ylikorkala O.

Objetives: Current recommendations for hormone therapy are mainly based on findings from studies using standard dose regimens in older women who had a different health profile from those who start HT soon after the onset of menopause. METHODS: We, therefore, reviewed controlled trials assessing the efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT) started for treatment of climacteric symptoms. This review is limited to oral cc-HT regimens over sequential regimens as most postmenopausal women prefer not to have a return of uterine bleeding, and to studies of at least 2 years in duration. RESULTS: Low-dose cc-HT is effective in alleviating climacteric symptoms and in maintaining bone density over prolonged periods, although no data were available regarding fracture risk. No increased risk of coronary heart disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was reported in the long-term studies and no definitive evidence for an increased risk of breast cancer was found. Breakthrough bleeding during the first months of use is less common than with standard dose HT and amenorrhoea is achieved in most women over time. These regimens are safe for the endometrium and are well tolerated, with a low incidence of adverse events compared with standard doses. Conclusions: Current evidence from controlled trials indicates that low-dose oral cc-HT appears effective and safe. This makes it a good choice for the alleviation of climacteric symptoms, and for this purpose long-term administration of low-dose cc-HT does not seem to impose serious health risks. However, more long-term study data and direct head-to-head comparisons between various low-dose preparations are needed to support or rectify the safety aspects.

Diabetes Res Clin Pract. 2006 Oct 9; [Epub ahead of print]

Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A.

Department of Medicina Sperimentale,  University of Catanzaro Magna Graecia, Catanzaro, Italy.

BACKGROUND: Obesity and the metabolic syndrome (MS) frequently coexist. Both are apparently associated to cardiovascular disease. However, the contribution of obesity to cardiovascular risk, independent of the presence of the metabolic syndrome, remains controversial. The purpose of this study was to investigate whether the subclinical carotid atherosclerosis prevalence is different in obese postmenopausal women with and without the metabolic syndrome. METHODS: On the basis of consecutive recruitment, 313 postmenopausal women underwent a clinical, biochemical and ultrasound characterization. Women affected by cardiovascular disease or diabetes were excluded from the study. RESULTS: Among enrolled women the metabolic syndrome and body mass index (BMI) resulted strongly associated, but only metabolic syndrome was associated with carotid atherosclerosis, a well-known marker of cardiovascular disease. Similarly, increases in BMI unit (normal to overweight to obese) were not associated with carotid atherosclerosis whereas metabolic status (normal to metabolic syndrome) conferred an approximate three-fold adjusted odds of carotid atherosclerosis. CONCLUSIONS: The metabolic syndrome but not obesity is associated to carotid atherosclerosis in postmenopausal women. Although it remains prudent to recommend weight loss in overweight and obese women, evaluation and control of metabolic risk factors should be considered the main goal to prevent cardiovascular and cerebrovascular disease.