Publications (48)610.36 Total impact
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Article: Walking speed, physical activity, and breast cancer in postmenopausal women.
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ABSTRACT: Higher self-reported physical activity is associated with lower breast cancer incidence and mortality. Objectively measured timed walking speed, predictive of longevity in older adults, has been associated with ambulatory physical activity in small studies but definitive assessment of the association is lacking. Participants were a subset of 14 719 postmenopausal women in the Women's Health Initiative study who, at entry, had 10 m, timed walking speed determined. After 12.4 years [mean (SD) (3.5)] follow-up, 762 invasive breast cancers were diagnosed in this group. In addition, 8162 of these women self-reported physical activity. Simple linear regression was used to examine the relationship between timed walking speed and self-reported physical activity. A Cox proportional hazard model was used to estimate age-adjusted hazard ratios and 95% confidence intervals for the association between timed walking speed and invasive breast cancer incidence. Although a linear regression model for self-reported physical activity [log metabolic equivalent task (MET) h/week] versus 10 m, timed walking speed had a statistically significant slope (coefficient=0.03, P<0.0001, correlation=0.20), the magnitude of the relationship was not clinically useful. Timed walking speed quintile was not associated with breast cancer incidence in age-adjusted or multivariant analyses (P for trend=0.60). Timed walking speed was not associated with self-reported physical activity in a clinically useful manner or with breast cancer incidence. Our findings do not support use of timed walking speed as an objective surrogate for self-reported physical activity.European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 05/2013; · 2.21 Impact Factor -
Article: Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women's Health Initiative Observational Study.
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ABSTRACT: Background In the Women's Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.ResultsAfter a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.CancerSpectrum Knowledge Environment 03/2013; · 14.07 Impact Factor -
Article: Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative.
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ABSTRACT: Bisphosphonates are widely-prescribed to increase bone density in postmenopausal women with osteopenia or osteoporosis. Amino-bisphosphonates have numerous anticancer properties and reduce bone-metastases in cancer patients. Several studies, including the Women's Health Initiative (WHI), have found that use of oral bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies in women such as colorectal cancer (CRC). A few case-control and retrospective cohort studies have reported decreased risk of CRC among bisphosphonate users. In contrast, a prospective cohort study found no association. We evaluated the association between oral bisphosphonate use and CRC incidence in 156,826 postmenopausal women, ages 50-79, who participated in WHI clinical trials and observational study. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly-used medications at baseline and over follow-up. A total of 1,931 women were diagnosed with incident invasive CRC during a median follow-up of 12 years. Alendronate was the most commonly used bisphosphonate, accounting for >90% of the total person-years of use. The association between oral bisphosphonate use and CRC risk did not reach statistical significance (hazard ratio [HR] from multivariable-adjusted models, 0.88; 95% confidence interval [CI], 0.72-1.07; P = 0.19). Furthermore, we did not observe greater risk reductions for women with longer duration of use. Uncontrolled confounding may explain why previous studies have observed an association. © 2013 American Society for Bone and Mineral Research.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2013; · 6.04 Impact Factor -
Article: Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women's Health Initiative.
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ABSTRACT: OBJECTIVES: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. DESIGN: Post hoc analysis of a randomized double-blind placebo-controlled trial. SETTING: Forty Women's Health Initiative (WHI) clinical centers across the United States. PARTICIPANTS: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. INTERVENTION: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo. MEASUREMENTS: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. RESULTS: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. CONCLUSION: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.Journal of the American Geriatrics Society 11/2012; · 3.74 Impact Factor -
Article: Recreational physical activity, body mass index, and survival in women with colorectal cancer.
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ABSTRACT: BACKGROUND AND PURPOSE: Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality. PATIENTS AND METHODS: This prospective cohort study included 1,339 women enrolled in the Women's Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrollment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis. RESULTS: Among women diagnosed with colorectal cancer, 265 (13 %) deaths occurred during a median study follow-up of 11.9 years, of which 171 (65 %) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of ≥18 MET-h/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR) = 0.68; 95 % confidence interval (CI): 0.41-1.13) and all-cause mortality (HR = 0.63; 95 % CI: 0.42-0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis. CONCLUSION: Recreational physical activity before and after colorectal cancer diagnosis, but not BMI, is associated with more favorable survival.Cancer Causes and Control 10/2012; · 2.88 Impact Factor -
Article: Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption, and breast cancer.
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ABSTRACT: Increased exposure to endogenous estrogen and/or insulin may partly explain the relationship of obesity, physical inactivity, and alcohol consumption and postmenopausal breast cancer. However, these potential mediating effects have not been formally quantified in a survival analysis setting. We combined data from two case-cohort studies based in the Women's Health Initiative-Observational Study with serum estradiol levels, one of which also had insulin levels. A total of 1,601 women (601 cases) aged 50 to 79 years who were not using hormone therapy at enrollment were included. Mediating effects were estimated by applying a new method based on the additive hazard model. A five-unit increase in body mass index (BMI) was associated with 50.0 [95% confidence interval (CI), 23.2-76.6] extra cases per 100,000 women at-risk per year. Of these, 23.8% (95% CI, 2.9-68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6-273.3) through insulin pathways. The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8-161.1) for BMI when restricted to estrogen receptor positive (ER(+)) cases. Consuming 7+ drinks/wk compared with abstinence was associated with 164.9 (95% CI, 45.8-284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found. The effect of alcohol on breast cancer was restricted to ER(+) breast cancers. The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin. The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk.Cancer Epidemiology Biomarkers & Prevention 05/2012; 21(7):1203-12. · 4.12 Impact Factor -
Article: Toward a Positive Aging Phenotype for Older Women: Observations From the Women's Health Initiative.
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ABSTRACT: To develop a positive aging phenotype, we undertook analyses to describe multiple dimensions of positive aging and their relationships to one another in women 65 years of age and older and evaluate the performance of individual indicators and composite factors of this phenotype as predictors of time to death, years of healthy living, and years of independent living. Data from Women's Health Initiative clinical trial and observational study participants ages 65 years and older at baseline, including follow-up observations up to 8 years later, were analyzed using descriptive statistics and principal components analysis to identify the factor structure of a positive aging phenotype. The factors were used to predict time to death, years of healthy living (without hospitalization or diagnosis of a serious health condition), and years of independent living (without nursing home admission or use of special services). We identified a multidimensional phenotype of positive aging that included two factors: Physical-Social Functioning and Emotional Functioning. Both factors were predictive of each of the outcomes, but Physical-Social Functioning was the strongest predictor. Each standard deviation of increase in Physical-Social Functioning was accompanied by a 23.7% reduction in mortality risk, a 19.4% reduction in risk of major health conditions or hospitalizations, and a 26.3% reduction in risk of dependent living. Physical-Social Functioning and Emotional Functioning constitute important components of a positive aging phenotype. Physical-Social Functioning was the strongest predictor of outcomes related to positive aging, including years of healthy living, years of independent living, and time to mortality.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 04/2012; 67(11):1191-6. · 4.60 Impact Factor -
Article: Body mass index and screening for colorectal cancer: gender and attitudinal factors.
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ABSTRACT: Overweight/obese women and men are at increased risk for colorectal cancer (CRC) incidence and mortality. Research examining body mass index (BMI) and CRC screening has had mixed results. A clearer understanding of the extent to which high-BMI subgroups are screened for CRC is needed to inform planning for CRC screening promotions targeting BMI. Data were obtained from a random, population-based sample of women and men at average-risk for CRC (aged 50-75 years) during 2004 (n = 1098). Multiple logistic regression analyses were conducted to evaluate whether BMI category was significantly associated with the probability of reporting recent CRC screening and with the probability of agreeing with statements denoting attitudes/perceptions about CRC and screening. Attitudes/perceptions about CRC and screening were evaluated as potential mediators and moderators of the association between BMI category and CRC screening. After controlling for characteristics associated with CRC screening, overweight and obese women were each 40% less likely to have CRC screening than women with normal-BMI (OR = 0.6, 95% CI:0.4-0.9 and OR = 0.6, 95% CI:0.3-0.9). BMI category was unrelated to screening among men. Obese women (but not men) were less aware than normal-BMI women that obesity increased risk for CRC (OR = 0.5, 95% CI:0.3-0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3-0.8). However, findings suggest that attitudes/perceptions about CRC and screening did not mediate or moderate the association between BMI category and CRC screening. Overweight/obese women are at increased risk for CRC because of their greater BMI and their propensity not to screen for CRC. Study findings suggest that potentially modifiable perceptions, e.g., lack of awareness of risk for CRC and less worry about CRC, in this subgroup may not explain the relationship between BMI category and reduced screening.Cancer epidemiology. 03/2012; 36(4):400-8. -
Article: Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer risk.
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ABSTRACT: To determine whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of colorectal cancer. The population included 159,219 postmenopausal women enrolled in the Women's Health Initiative in which 2000 pathologically confirmed cases of colorectal cancer were identified during an average of 10.7 (S.D. 2.9) years. Information on statins was collected at baseline and years 1, 3, 6, and 9. Self- and interviewer-administered questionnaires were used to collect information on other risk factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the use of Cox proportional hazards regression to evaluate the relationship between statin use and risk. Statistical tests were two-sided. Statins were used by 12,030 (7.6%) women at baseline. The annualized colorectal cancer rate was 0.13% among users and 0.12% among nonusers. The multivariable adjusted HR for users versus nonusers was 0.99 (95% confidence interval [CI], 0.83-1.20, p = .95), and 0.79 (95% CI, 0.56-1.11) for users of ≥3 years. In the multivariable adjusted time-dependent model, the HR for lovastatin was 0.62 (95% CI, 0.39-0.99). There was no effect of tumor location, stage or grade. There was a reduction in colorectal cancer risk associated with lovastatin and a nonsignificant association with longer duration of use.Annals of epidemiology 11/2011; 22(1):17-27. · 2.95 Impact Factor -
Article: Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative.
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ABSTRACT: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.Menopause (New York, N.Y.) 11/2011; 18(11):1160-71. · 3.08 Impact Factor -
Article: Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative
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ABSTRACT: Objective: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). Methods: Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Results: Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Conclusions: Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.Menopause 10/2011; 18(11):1160-1171. · 3.76 Impact Factor -
Article: Dietary glycemic load, glycemic index, and carbohydrate and risk of breast cancer in the Women's Health Initiative.
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ABSTRACT: Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women's Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92-1.29 (P for trend = 0.27); 1.01, 0.91-1.12 (P = 0.74); and 0.95, 0.80-1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94-2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.Nutrition and Cancer 06/2011; 63(6):899-907. · 2.78 Impact Factor -
Article: Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers.
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ABSTRACT: Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.CancerSpectrum Knowledge Environment 02/2011; 103(7):562-70. · 14.07 Impact Factor -
Article: Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.
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ABSTRACT: In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants. Invasive breast cancer incidence and breast cancer mortality. In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. clinicaltrials.gov Identifier: NCT00000611.JAMA The Journal of the American Medical Association 10/2010; 304(15):1684-92. · 30.03 Impact Factor -
Article: Oral bisphosphonate use and breast cancer incidence in postmenopausal women.
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ABSTRACT: Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence. The association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations. To adjust for potential BMD difference based on bisphosphonate use, the hip fracture prediction score was included in multivariant analyses as a BMD surrogate. Of the 154,768 participants, 2,816 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). As calculated hip fracture risk score was significantly associated with both BMD (regression line = 0.79 to 0.0478 log predicted fracture; P < .001; r = 0.43) and breast cancer incidence (P = .03), this variable was incorporated into regression analyses to adjust for BMD difference between users and nonusers of bisphopshonate. After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) -positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). A similar but not significant trend was seen for ER-negative invasive cancers. The incidence of ductal carcinoma in situ was higher in bisphosphonate users (HR, 1.58; 95% CI, 1.08 to 2.31; P = .02). Oral bisphosphonate use was associated with significantly lower invasive breast cancer incidence, suggesting bisphosphonates may have inhibiting effects on breast cancer.Journal of Clinical Oncology 08/2010; 28(22):3582-90. · 18.37 Impact Factor -
Article: An academic medical center model for community colorectal cancer screening: the Centers for Disease Control and Prevention demonstration program experience.
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ABSTRACT: During 2005-2009, the Centers for Disease Control and Prevention funded five colorectal cancer (CRC) screening demonstration projects around the United States; only one was based in an academic medical center (AMC) rather than a health department. The Suffolk County Preventive Endoscopy Project (Project SCOPE) was a collaborative effort between Stony Brook University Medical Center (SBUMC) and the Suffolk County Department of Health Services. Project SCOPE's objective was to increase CRC screening among Suffolk County residents at least 50 years old who had inadequate or no insurance coverage for CRC screening. The demonstration application drew on the screening, diagnostic, and treatment resources of the AMC and the indigent populations using its outpatient clinics. Patients at 10 county health centers were a primary target for (previously inaccessible) colonoscopy screening. The project's organizational center was SBUMC's preventive medicine department, which was linked to SBUMC's large gastroenterology practice. The specific staffing, financial, and training issues faced by this project provide insights for others who are similarly interested in community engagement. During 40 months of screening, 800 indigent, culturally diverse patients were recruited, and they underwent colonoscopy. Challenges encountered included unreachable referred patients (425 patients; 28% of referrals) and medical ineligibility (e.g., symptomatic comorbid conditions). Pending legislation providing federal funding for a national program offers other AMCs the opportunity to adopt a model such as that proven feasible during Project SCOPE. The lessons learned may have broader application for fostering collaborative AMC partnerships and for enhancing recruitment and retention of participants through outreach.Academic medicine: journal of the Association of American Medical Colleges 05/2010; 85(8):1354-61. · 2.34 Impact Factor -
Article: Relative effects of tamoxifen, raloxifene, and conjugated equine estrogens on cognition.
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ABSTRACT: To compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years. Annual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function in the two randomized placebo-controlled clinical trials of CEE therapies of the Women's Health Initiative Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential ethnic-related differences between studies, to Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with placebo therapy while controlling for differences between groups with respect to dementia risk factors. At baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was associated with a small mean relative deficit in 3MS scores of < or =0.5 units, which was fairly consistent between women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001) and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative deficits appeared to be greater among women with lower baseline 3MS scores: p = 0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE). Although unmeasured differences between trials may have confounded analyses, these findings raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women; however, the magnitude of the effect is small, and the long-term consequences are unknown.Journal of Women s Health 02/2010; 19(3):371-9. · 1.57 Impact Factor -
Article: The relationship between cognitive function and physical performance in older women: results from the women's health initiative memory study.
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ABSTRACT: Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear. In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change. Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p </= .01 both). Changes in 3MS and PPM were associated, particularly with chair stands and grip strength (p < .003 both). Baseline PPMs were not associated with subsequent 3MS change. Baseline global cognitive function and change in global cognitive function were associated with physical performance change, but baseline physical performance was not associated with cognitive change in this cohort. These analyses support the hypothesis that cognitive decline on average precedes or co-occurs with physical performance decline.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2009; 65(3):300-6. · 4.60 Impact Factor -
Article: Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause.
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ABSTRACT: The authors further analyzed results from the Women's Health Initiative randomized trials (1993-2004) of conjugated equine estrogens, with or without medroxyprogesterone acetate, focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause. Data from the Women's Health Initiative observational study (1993-2004) were included in some analyses for additional precision. Results are presented here for incident coronary heart disease, stroke, venous thromboembolism, breast cancer, colorectal cancer, endometrial cancer, or hip fracture; death from other causes; a summary global index; total cancer; and total mortality. Hazard ratios for breast cancer and total cancer were comparatively higher (P < 0.05) among women who initiated hormone therapy soon after menopause, for both regimens. Among these women, use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture. Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism, stroke, and hip fracture but also included evidence of longer-term elevations in breast cancer, total cancer, and the global index. These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause, either for coronary heart disease or for health benefits versus risk indices considered.American journal of epidemiology 07/2009; 170(1):12-23. · 5.59 Impact Factor -
Article: Breast cancer after use of estrogen plus progestin in postmenopausal women.
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ABSTRACT: Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial. We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use. In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged. The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.New England Journal of Medicine 03/2009; 360(6):573-87. · 53.30 Impact Factor
Top Journals
Institutions
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2008–2010
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Stony Brook University
- Department of Preventive Medicine
Stony Brook, NY, USA
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2007
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Fred Hutchinson Cancer Research Center
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Seattle, WA, USA
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2006
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Stanford University
- Department of Medicine
Stanford, CA, USA
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2003–2006
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University of California, Davis
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