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1.  Menstrual and reproductive characteristics and breast density in young women 
Cancer causes & control : CCC  2013;24(11):1973-1983.
Purpose
Breast density is strongly related to breast cancer risk, but determinants of breast density in young women remain largely unknown.
Methods
Associations of reproductive and menstrual characteristics with breast density measured by magnetic resonance imaging were evaluated in a cross-sectional study of 176 healthy women, 25–29 years old, using linear mixed effects models.
Results
Parity was significantly inversely associated with breast density. In multivariable adjusted models that included non-reproductive variables, mean percent dense breast volume (%DBV) decreased from 20.5 % in nulliparous women to 16.0 % in parous women, while mean absolute dense breast volume (ADBV) decreased from 85.3 to 62.5 cm3. Breast density also was significantly inversely associated with the age women started using hormonal contraceptives, whereas it was significantly positively associated with duration of hormonal contraceptive use. In adjusted models, mean %DBV decreased from 21.7 % in women who started using hormones at 12–17 years of age to 14.7 % in those who started using hormones at 22–28 years of age, while mean ADBV decreased from 86.2 to 53.7 cm3. The age at which women started using hormonal contraceptives and duration of hormone use were inversely correlated, and mean %DBV increased from 15.8 % in women who used hormones for not more than 2.0 years to 22.0 % in women who used hormones for more than 8 years, while mean ADBV increased from 61.9 to 90.4 cm3 over this interval.
Conclusions
Breast density in young women is inversely associated with parity and the age women started using hormonal contraceptives but positively associated with duration of hormone use.
doi:10.1007/s10552-013-0273-2
PMCID: PMC3960004  PMID: 23933948
Breast density; Parity; Breast feeding; Hormonal contraceptives; Menarche; Menstrual cycle
2.  Thiazolidinediones, Cardiovascular Disease and Cardiovascular Mortality: Translating Research Into Action For Diabetes (TRIAD) 
Background
Studies have associated thiazolidinedione (TZD) treatment with cardiovascular disease (CVD) and questioned whether the two available TZDs, rosiglitazone and pioglitazone, have different CVD risks. We compared CVD incidence, cardiovascular (CV) and all-cause mortality in type 2 diabetic patients treated with rosiglitazone or pioglitazone as their only TZD.
Methods
We analyzed survey, medical record, administrative, and National Death Index (NDI) data from 1999 through 2003 from Translating Research Into Action for Diabetes (TRIAD), a prospective observational study of diabetes care in managed care. Medications, CV procedures, and CVD were determined from health plan (HP) administrative data, and mortality was from NDI. Adjusted hazard rates (AHR) were derived from Cox proportional hazard models adjusted for age, sex, race/ethnicity, income, history of diabetic nephropathy, history of CVD, insulin use, and HP.
Results
Across TRIAD’s ten HPs, 1,815 patients (24%) filled prescriptions for a TZD, 773 (10%) for only rosiglitazone, 711 (10%) for only pioglitazone, and 331 (4%) for multiple TZDs. In the seven HPs using both TZDs, 1,159 patients (33%) filled a prescription for a TZD, 564 (16%) for only rosiglitazone, 334 (10%) for only pioglitazone, and 261 (7%) for multiple TZDs. For all CV events, CV and all-cause mortality, we found no significant difference between rosiglitazone and pioglitazone.
Conclusions
In this relatively small, prospective, observational study, we found no statistically significant differences in CV outcomes for rosiglitazone- compared to pioglitazone-treated patients. There does not appear to be a pattern of clinically meaningful differences in CV outcomes for rosiglitazone- versus pioglitazone-treated patients.
doi:10.1002/pds.1954
PMCID: PMC3548906  PMID: 20583206
Thiazolidinediones; rosiglitazone; pioglitazone; diabetes
3.  Usefulness of Baseline Lipids and C-Reactive Protein in Women Receiving Menopausal Hormone Therapy as Predictors of Treatment-Related Coronary Events 
The American journal of cardiology  2008;101(11):1599-1605.
Blood lipids and high sensitivity C-reactive protein (hsCRP) are altered by hormone therapy. The goal of the current study was to determine whether lipids and hsCRP have predictive value for hormone therapy benefit or risk for coronary heart disease (CHD) events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women’s Health Initiative hormone trials. Baseline lipids and hsCRP were obtained from 271 incident CHD cases and 707 controls. In a combined trial analysis, a favorable lipid status at baseline tended to predict better CHD outcomes when taking conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low density lipoprotein (LDL)/high density lipoprotein (HDL) ratio <2.5 had no increase in risk of CHD when taking CEE with or without MPA (OR 0.60, 95%CI=0.34–1.06), whereas women with an LDL/HDL ratio ≥2.5 had an increased risk of CHD (OR 1.73, 95%CI=1.18–2.53) (p-value for interaction = 0.02). Low hsCRP levels added marginally to the value of LDL/HDL<2.5 when predicting CHD benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess CHD risk when using CEE with or without MPA; however, women with favorable lipid levels, especially an LDL/HDL ratio < 2.5, did not have an elevated risk of CHD with CEE with or without MPA, irrespective of hsCRP levels.
doi:10.1016/j.amjcard.2008.01.043
PMCID: PMC3543778  PMID: 18489937
CHD; hormone therapy; lipids; cholesterol
4.  Height, adiposity and body fat distribution and breast density in young women 
Breast Cancer Research : BCR  2012;14(4):R107.
Introduction
Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown.
Methods
Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided.
Results
Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV.
Conclusion
Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.
doi:10.1186/bcr3228
PMCID: PMC3680938  PMID: 22800711
5.  Evaluation of risk equations for prediction of short-term coronary heart disease events in patients with long-standing type 2 diabetes: the Translating Research into Action for Diabetes (TRIAD) study 
Background
To evaluate the U.K. Prospective Diabetes Study (UKPDS) and Framingham risk equations for predicting short-term risk of coronary heart disease (CHD) events among adults with long-standing type 2 diabetes, including those with and without preexisting CHD.
Methods
Prospective cohort of U.S. managed care enrollees aged ≥ 18 years and mean diabetes duration of more than 10 years, participating in the Translating Research into Action for Diabetes (TRIAD) study, was followed for the first occurrence of CHD events from 2000 to 2003. The UKPDS and Framingham risk equations were evaluated for discriminating power and calibration.
Results
A total of 8303 TRIAD participants, were identified to evaluate the UKPDS (n = 5914, 120 events), Framingham-initial (n = 5914, 218 events) and Framingham-secondary (n = 2389, 374 events) risk equations, according to their prior CHD history. All of these equations exhibited low discriminating power with Harrell’s c-index <0.65. All except the Framingham-initial equation for women and the Framingham-secondary equation for men had low levels of calibration. After adjsusting for the average values of predictors and event rates in the TRIAD population, the calibration of these equations greatly improved.
Conclusions
The UKPDS and Framingham risk equations may be inappropriate for predicting the short-term risk of CHD events in patients with long-standing type 2 diabetes, partly due to changes in medications used by patients with diabetes and other improvements in clinical care since the Frmaingham and UKPDS studies were conducted. Refinement of these equations to reflect contemporary CHD profiles, diagnostics and therapies are needed to provide reliable risk estimates to inform effective treatment.
doi:10.1186/1472-6823-12-12
PMCID: PMC3433369  PMID: 22776317
6.  Adolescent Diet and Subsequent Serum Hormones, Breast Density and Bone Mineral Density in Young Women: Results of the Dietary Intervention Study in Children (DISC) Follow-Up Study 
Background
Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults.
Methods
A follow-up study was conducted of 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal 8-10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25-29 years old at follow-up visits. All tests of statistical significance are two-sided.
Results
In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content (BMC) in intervention group participants compared to usual care group participants; their mean BMCs were 2,444g and 2,377g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses.
Conclusion
Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density or BMD.
Impact
Additional research is needed to clarify the association of adolescent diet with breast cancer risk and to determine if the results reported here are specific to the DISC intervention or more broadly applicable.
doi:10.1158/1055-9965.EPI-09-1259
PMCID: PMC2883023  PMID: 20501774
7.  Estrogen plus Progestin and Risk of Benign Proliferative Breast Disease 
Women with benign proliferative breast disease are at increased risk of subsequent breast cancer. Estrogens and progesterone exert proliferative effects on mammary epithelium and combined hormone replacement therapy has been associated with increased breast cancer risk. We tested the effect of conjugated equine estrogen plus progestin on risk of benign proliferative breast disease in the Women's Health Initiative (WHI) randomized controlled trial. In the WHI trial of estrogen plus progestin, 16608 postmenopausal women were randomly assigned either to 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate or to placebo. Baseline and annual breast exams and mammograms were required. The trial was terminated early (average follow-up, 5.5 years). We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. Overall, 178 incident cases of benign proliferative breast disease were ascertained in the estrogen plus progestin group and 99 in the placebo group. Use of estrogen plus progestin was associated with a 74% increase in risk of benign proliferative breast disease (hazard ratio 1.74, 95% CI 1.35-2.25). For benign proliferative breast disease without atypia the hazard ratio was 2.00 (95% CI 1.50-2.66), while for atypical hyperplasia it was 0.76 (95% CI 0.38-1.52). Risk varied little by levels of baseline characteristics. The results of this study suggest that use of estrogen plus progestin may increase the risk of benign proliferative breast disease.
doi:10.1158/1055-9965.EPI-08-0380
PMCID: PMC2584343  PMID: 18725513
estrogen; progestin; benign proliferative breast disease

Results 1-7 (7)