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Context: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.Objective: To determine whether women taking raloxifene have a lower risk of invasive breast cancer.Design and Setting: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.Participants: A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.Intervention: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome Measures: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.Results: Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).Conclusion: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene. [ABSTRACT FROM AUTHOR]

Objective: To determine factors that influence the sensitivity of modern first screening mammography.Design: Cross-sectional.Setting: Nine counties in northern California.Participants: A total of 28 271 women aged 30 years and older referred for first screening mammography to the Mobile Mammography Screening Program of the University of California, San Francisco, from April 1985 to March 1992, of whom 238 were subsequently diagnosed as having breast cancer.Measurements: Breast cancer risk profile, 2 standard mammographic views per breast, breast density, and follow-up of abnormal and normal mammography by contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results tumor registry to determine the occurrence of any invasive cancer or ductal carcinoma in situ.Results: For women aged 50 years and older, the sensitivity of first screening mammography was relatively high and decreased slightly with increasing length of follow-up after mammography: 98.5% for 7 months of follow-up, 93.2% for 13 months, and 85.7% for 25 months. Sensitivity was higher among women aged 50 years and older when breast density was primarily fatty rather than primarily dense (98.4% vs 83.7%; P < .01). For women younger than 50 years, the sensitivity of first screening mammography also decreased with increasing length of follow-up but was significantly lower than for older women: 87.5% for 7 months of follow-up, 83.6% for 13 months, and 71.4% for 25 months. For women younger than 50 years, breast density did not affect the sensitivity of mammography (81.8% for those with primarily fatty breasts vs 85.4% for those with primarily dense breasts) and was lower among those with a family history of breast cancer (68.8%).Conclusions: The sensitivity of modern mammography is highest among women aged 50 years and older who have primarily fatty breast density. Sensitivity is lowest among women younger than 50 years and particularly low when the time between screenings is about 2 years or when women have a family history of breast cancer, possibly because of rapid tumor growth. [ABSTRACT FROM AUTHOR]

Objective: To determine the sensitivity, specificity, and likelihood ratios (LRs) for modern screening mammography by decade of age and mammographic interpretation.Design: Cross-sectional.Setting: Nine counties in northern California.Participants: A total of 26,057 women aged 30 years and older who underwent a total of 41,747 first and subsequent screening mammographic examinations at the Mobile Mammography Screening Program of the University of California, San Francisco, from April 1985 to September 1991.Measurements: Breast cancer risk profile, 2 standard mammographic views per breast, and follow-up of abnormal and normal mammograms of contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results tumor registry. False-negative examinations were normal examinations that occurred within 13 months of a diagnosis of invasive breast cancer or ductal carcinoma in situ.Results: The sensitivity of first screening mammography increased with age: 77.3% for ages 30 to 39 years, 86.7% for ages 40 to 49 years, 93.6% for ages 50 to 59 years, 94.1% for ages 60 to 69 years, and 91.2% for ages 70 years and older (P = .04). Specificity was similar for all ages, ranging from 92.6% to 95.2%. Of all abnormal first screening examinations, 92.9% were reported as "additional evaluation needed." The LRs for that category ranged from 5.2 to 8.8 and did not vary with age. Based on the risk of breast cancer before mammography, which increases with age, the risk of breast cancer after mammography associated with these LRs were 0.01 for ages 30 to 39 years, 0.02 for ages 40 to 49 years, 0.05 for ages 50 to 59 years, 0.07 for ages 60 to 69 years, and 0.07 for ages 70 years and older. The LRs for mammography reported as "suspicious for malignancy" ranged from 88 to 144 and did not vary across age groups. These LRs were associated with a risk of breast cancer about 10 times greater than when mammography was reported as "additional evaluation needed."Conclusion: Most abnormal first screening mammography are interpreted as "additional evaluation needed" and are associated with LRs of about 7. Given this low LR, the risk of breast cancer after mammography is primarily influenced by a woman's age-specific risk of breast cancer before mammography. The LRs for screening mammography interpreted as "suspicious for malignancy" are high (about 124) and are associated with a substantial increase in the risk of breast cancer irrespective of age, but these interpretations comprise only a small proportion of abnormal mammography. [ABSTRACT FROM AUTHOR]

Objective: To assess the evidence that lipid lowering prevents coronary heart disease (CHD) events in women.Data Sources: English-language literature assessing the effects of cholesterol lowering with dietary and/or drug interventions as primary or secondary prevention on CHD events in women.Main Outcome Measures: Coronary heart disease and total mortality were the primary outcomes assessed. Angiographic regression of coronary atherosclerosis was a secondary outcome. STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: All nine of the identified studies that met the criteria were included. Relative risks for CHD and total mortality were calculated from available data. Summary relative risks were calculated using meta-analytic techniques.Conclusions: There is no evidence from primary prevention trials that cholesterol lowering affects total mortality in healthy women, although the available data are limited. Limited evidence suggests that treatment of hypercholesterolemia in women with coronary disease may decrease CHD mortality. Future research should address the role of dietary and other nondrug treatment of hypercholesterolemia in women at high risk for CHD. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up.Design: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects.Main Results: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up.Conclusion: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age. [ABSTRACT FROM AUTHOR]

Objective: To determine the positive predictive value (PPV) of low-cost screening mammography according to age and family history of breast cancer.Design: Cross-sectional.Setting: Six counties in northern California.Participants: A total of 31,814 women aged 30 years and older referred for mammography to the University of California, San Francisco, Mobile Mammography Screening Program from April 18, 1985, through November 20, 1992.Measurements: Breast cancer risk profile, two standard mammographic views per breast, and follow-up of abnormal screening examinations.Results: Although women aged 50 years or older constituted only 38.3% of all women who received first-screening mammography, 74% of breast cancers were detected in this group. Ten cancers were diagnosed per 1000 first-screening examinations in women aged 50 years or older, with 14.8 diagnostic procedures per cancer diagnosed compared with two cancers per 1000 screening examinations and 48.3 diagnostic tests per cancer diagnosed in women younger than 50 years. The PPV of first-screening mammography (number of breast cancers detected per abnormal examination) increased with age: .03 for those aged 30 to 39 years; .04 for those aged 40 to 49; .09 for those aged 50 to 59; .17 for those aged 60 to 69; and .19 for those aged 70 years or older (chi 2 for trend, P < .001). Women aged 50 to 59 years had a higher PPV for first-screening mammography than women aged 40 to 49 years (.09 vs. .04; P = .004), and women with a family history of breast cancer had higher PPVs compared with women without history (40 to 49 years of age, .13 vs .04, P = .01; and 50 to 59 years of age, .22 vs .09, P = .01).Conclusion: Five times as many cancers per 1000 first-screening mammographic examinations were diagnosed in women aged 50 years or older compared with women aged less than 50 years. The highest PPVs for mammography were in women aged 50 years or older and in women aged 40 years or older with a family history of breast cancer. Efforts to promote screening mammography should focus on women in these groups, in whom the majority of breast cancers occur and for whom mammography has the highest PPVs. [ABSTRACT FROM AUTHOR]

Context: Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.Objective: To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.Design: Randomized, blinded, placebo-controlled secondary prevention trial.Setting: Outpatient and community settings at 20 US clinical centers.Participants: A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention: Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures: The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.Results: Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions: During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ (DCIS) accounts for approximately 12% of newly diagnosed breast cancers. Knowledge of the factors that predict who will be diagnosed with DCIS is very limited.Purpose: The goal of this study was to determine risk factors associated with DCIS and whether these risk factors are similar to those associated with invasive breast cancer.Methods: We conducted a cross-sectional study of 39,542 women aged 30 years and older who underwent a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program from April 1985 through September 1995. A breast cancer risk profile and clinical history were obtained for each woman. Follow-up after abnormal mammography was performed to determine the presence of DCIS or invasive breast cancer by contacting the women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results cancer registry. Multivariate analysis was performed by the use of polytomous logistic regression. Two-sided statistical tests were used to determine P values.Results: Among women aged 30-49 years, a family history of breast cancer (i.e., at least one affected first degree relative) was associated with an increased risk of DCIS (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-4.9) and body mass index greater than or equal to 25 kg/m2 was associated with a decreased risk of DCIS (OR = 0.4, 95% CI = 0.2 to 0.9). For each of these factors, there was a trend in the same direction bordering on statistical significance for invasive cancer (ORs = 1.7 [95% CI = 0.9-3.4] and 0.6 [95% CI = 0.3-1.1], respectively). Report of a palpable mass was associated with an increased risk of invasive cancer among women aged 30-49 years (OR = 12.0; 95% CI = 7.1-20.0); there was a trend in the same direction for DCIS (OR = 2.0; 95% CI = 0.8-5.1), but the association was much stronger for invasive disease than for DCIS (OR = 6.0; 95% CI = 2.1-18.0; P = .001). Among women aged 50 years and older, family history of breast cancer and nulliparity or age at birth of first child of 30 years or older increased the risk of both DCIS (ORs = 2.2 [95% CI = 1.0-4.2] and 2.3 [95% CI = 1.3-3.8], respectively) and invasive breast cancer (ORs = 1.5 [95% CI = 1.0-2.2] and 1.6 [95% CI = 1.2-2.1], respectively). Report of a palpable mass was not associated with an increased risk of DCIS among women 50 years and older, but it was strongly associated with an increased risk of invasive cancer (OR = 9.3; 95% CI = 6.0-14.0). Increasing age was associated with an increased risk of both DCIS and invasive cancer among women aged 30-49 years, but the association was stronger for invasive disease; a trend in the same direction bordering on statistical significance was observed for women aged 50 years and older.Conclusion: Risk factors for DCIS are similar to those for invasive breast cancer.Implications: More research is needed to better understand the malignant potential of DCIS lesions and factors that predict which lesions will become invasive breast cancer if left untreated. [ABSTRACT FROM AUTHOR]

Context: Several studies have suggested that estrogen replacement therapy in postmenopausal women improves cognition, prevents development of dementia, and improves the severity of dementia, while other studies have not found a benefit of estrogen use.Objective: To determine whether postmenopausal estrogen therapy improves cognition, prevents development of dementia, or improves dementia severity.Data Sources: We performed a literature search of studies published from January 1966 through June 1997, using MEDLINE, manually searched bibliographies of articles identified, and consulted experts.Study Selection: Studies that evaluated biological mechanisms of estrogen's effect on the central nervous system and studies that addressed the effect of estrogen on cognitive function or on dementia.Data Extraction: We reviewed studies for methods, sources of bias, and outcomes and performed a meta-analysis of the 10 studies of postmenopausal estrogen use and risk of dementia using standard meta-analytic methods.Data Synthesis: Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia. Five observational studies and 8 trials have addressed the effect of estrogen on cognitive function in nondemented postmenopausal women. Cognition seems to improve in perimenopausal women, possibly because menopausal symptoms improve, but there is no clear benefit in asymptomatic women. Ten observational studies have measured the effect of postmenopausal estrogen use on risk of developing dementia. Meta-analysis of these studies suggests a 29% decreased risk of developing dementia among estrogen users, but the findings of the studies are heterogeneous. Four trials of estrogen therapy in women with Alzheimer disease have been conducted and have had primarily positive results, but most have been small, of short duration, non-randomized, and uncontrolled.Conclusions: There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia, or improvement in the severity of dementia. Studies conducted in women, however, have substantial methodologic problems and have produced conflicting results. Large placebo-controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias. Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of myocardial infarction (MI) and death in patients with unstable angina who are treated with aspirin plus heparin compared with patients treated with aspirin alone.Data Sources: Studies were retrieved using MEDLINE, bibliographies, and consultation with experts.Study Selection: Only published trials that enrolled patients with unstable angina, randomized participants to aspirin plus heparin vs aspirin alone, and reported incidence of myocardial infarction or death were included in the meta-analysis.Data Extraction: Patient outcomes including MI or death, recurrent ischemic pain, and major bleeding during randomized treatment; revascularization procedures after randomization; and MI or death during the 2 to 12 weeks following randomization were extracted by 2 authors, 1 of whom was blinded to the journal, institution, and author of each study.Data Synthesis: Six randomized trials were included. The overall summary relative risk (RR) of MI or death during randomized treatment was 0.67 (95% confidence interval [CI], 0.44-1.02) in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The summary RRs for secondary endpoints in patients treated with aspirin plus heparin compared with those treated with aspirin alone were 0.68 (95% CI, 0.40-1.17) for recurrent ischemic pain; 0.82 (95% CI, 0.56-1.20) for MI or death 2 to 12 weeks following randomization; 1.03 (95% CI, 0.74-1.43) for revascularization; and 1.99 (95% CI, 0.52-7.65) for major bleeding. We found no statistically significant heterogeneity among individual study findings.Conclusions: Our findings are consistent with a 33% reduction in risk of MI or death in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The bulk of evidence suggests that most patients with unstable angina should be treated with both heparin and aspirin. [ABSTRACT FROM AUTHOR]