-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: While low physical activity and high body mass index (BMI) have been associated with higher endometrial cancer incidence, no previous studies have evaluated the association between physical activity and survival after endometrial cancer diagnosis, and studies on BMI and survival have not been performed in a prospective cohort. METHODS: We examined pre-diagnosis BMI and moderate- to vigorous-intensity physical activity in relation to overall and disease-specific survival among 983 postmenopausal women who were diagnosed with endometrial cancer in the Women's Health Initiative Observational Study and Clinical Trials. RESULTS: Over a median 5.2 (max 14.1) years from diagnosis to death or end of follow-up, 163 total deaths were observed, 66 of which were due to endometrial cancer. We observed a higher all-cause mortality hazard ratio (HR)=1.85 (95% CI 1.19-2.88) comparing women with a BMI ≥35kg/m(2) to women with BMI <25kg/m(2). For endometrial cancer-specific mortality the HR=2.23 (95% CI 1.09-4.54) comparing extreme BMI categories. To examine histologic subtypes we analyzed type I endometrial tumors separately and found a HR=1.20 (95% CI 1.07-1.35) associated with all-cause mortality for each 5-unit change in BMI. Moderate- to vigorous-intensity physical activity was not associated with all-cause or endometrial cancer-specific mortality. CONCLUSIONS: Pre-diagnosis BMI, but not physical activity, was associated with survival among women with endometrial cancer. Future studies should investigate mechanisms and timing of BMI onset to better understand the burden of disease attributable to BMI.
Gynecologic Oncology 11/2012; · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epidemiological evidence of diabetes as a lung cancer risk factor is limited and conflicting. Therefore, we assessed associations among diabetes, diabetes therapy, and lung cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI) study.
Postmenopausal women (n = 145,765), ages 50-79 years, including 8,154 women with diabetes at study entry were followed for a mean of 11 years with 2,257 lung cancers diagnosed. Information on diabetes therapy was collected via two methods (self-reported information on treatment history collected on a questionnaire at baseline and a face-to-face review of current medication containers that participants brought to the baseline visit). Lung cancers were confirmed by central medical record and pathology report review. Cox proportional hazards regression models adjusted for lung cancer risk factors were used to estimate hazard ratios (HRs) (95% CI) for diagnosis of diabetes and treatment of disease as risk factors for lung cancer.
Compared with women without diabetes, women with self-reported treated diabetes had a significantly higher risk of lung cancer (HR 1.27 [95% CI 1.02-1.59]), with risks increasing for women with diabetes requiring insulin treatment (1.71 [1.15-2.53]). However, we did not observe a significant association between lung cancer risk and diabetes not treated with medication or with duration of diabetes.
Postmenopausal women with treated diabetes, especially those using insulin, have a significantly higher risk of lung cancer. The influence of diabetes severity and specific classes of therapy for diabetes on lung cancer risk require future study.
Diabetes care 05/2012; 35(7):1485-91. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Though larger social networks are associated with reduced breast cancer mortality, there is a need to clarify how both social support and social burden influence this association. We included 4,530 women from the Women's Health Initiative who were diagnosed with breast cancer between 1993 and 2009, and provided data on social networks (spouse or intimate partner, religious ties, club ties, and number of first-degree relatives) before diagnosis. Of those, 354 died during follow-up, with 190 from breast cancer. We used Cox proportional hazards regression to evaluate associations of social network members with risk of post-diagnosis mortality, further evaluating associations by social support and social burden (caregiving, social strain). In multivariate-adjusted analyses, among women with high but not low social support, being married was related to lower all-cause mortality. By contrast, among women with high but not low social burden, those with a higher number of first-degree relatives, including siblings, parents, and children, had higher all-cause and breast cancer mortality (among caregivers: 0-3 relatives (ref), 4-5 relatives, HR = 1.47 (95% CI: 0.62-3.52), 6-9 relatives, HR = 2.08 (95% CI: 0.89-4.86), 10+ relatives, HR = 3.55 (95% CI: 1.35-9.33), P-continuous = 0.02, P-interaction = 0.008). The association by social strain was similar though it was not modified by level of social support. Other social network members were unrelated to mortality. Social relationships may have both adverse and beneficial influences on breast cancer survival. Clarifying these depends on understanding the context of women's relationships.
Breast Cancer Research and Treatment 02/2012; 133(1):375-85. · 4.43 Impact Factor
-
Phoebe Lee,
Yi-Ping Fu,
Jonine D Figueroa,
Ludmila Prokunina-Olsson,
Jesus Gonzalez-Bosquet,
Peter Kraft,
Zhaoming Wang,
Kevin B Jacobs,
Meredith Yeager,
Marie-Josèphe Horner, [......], Rowan Chlebowski,
Jolanta Lissowska,
Beata Peplonska,
Louise A Brinton,
Margaret Tucker,
Joseph F Fraumeni,
Robert N Hoover,
Gilles Thomas,
David J Hunter,
Stephen J Chanock
[show abstract]
[hide abstract]
ABSTRACT: In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) genome-wide association study of breast cancer, a single nucleotide polymorphism (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast cancer risk. In order to fine map this region, we imputed a 3.93 MB region flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576 controls) using the combined reference panels of the HapMap 3 and the 1000 Genomes Project. Single-marker association testing and variable-sized sliding-window haplotype analysis were performed, and for both analyses the initial tagging SNP rs999737 retained the strongest association with breast cancer risk. Investigation of contiguous regions did not reveal evidence for an additional independent signal. Therefore, we conclude that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation.
Human Genetics 09/2011; 131(3):479-90. · 5.07 Impact Factor
-
Melinda L Irwin,
Anne McTiernan,
JoAnn E Manson,
Cynthia A Thomson,
Barbara Sternfeld,
Marcia L Stefanick,
Jean Wactawski-Wende,
Lynette Craft,
Dorothy Lane,
Lisa W Martin, Rowan Chlebowski
[show abstract]
[hide abstract]
ABSTRACT: Although studies have shown that physically active breast cancer survivors have lower all-cause mortality, the association between change in physical activity from before to after diagnosis and mortality is not clear. We examined associations among pre- and postdiagnosis physical activity, change in pre- to postdiagnosis physical activity, and all-cause and breast cancer-specific mortality in postmenopausal women. A longitudinal study of 4,643 women diagnosed with invasive breast cancer after entry into the Women's Health Initiative study of postmenopausal women. Physical activity from recreation and walking was determined at baseline (prediagnosis) and after diagnosis (assessed at the 3 or 6 years post-baseline visit). Women participating in 9 MET-h/wk or more (∼ 3 h/wk of fast walking) of physical activity before diagnosis had a lower all-cause mortality (HR = 0.61; 95% CI, 0.44-0.87; P = 0.01) compared with inactive women in multivariable adjusted analyses. Women participating in ≥ 9 or more MET-h/wk of physical activity after diagnosis had lower breast cancer mortality (HR = 0.61; 95% CI, 0.35-0.99; P = 0.049) and lower all-cause mortality (HR = 0.54; 95% CI, 0.38-0.79; P < 0.01). Women who increased or maintained physical activity of 9 or more MET-h/wk after diagnosis had lower all-cause mortality (HR = 0.67; 95% CI, 0.46-0.96) even if they were inactive before diagnosis. High levels of physical activity may improve survival in postmenopausal women with breast cancer, even among those reporting low physical activity prior to diagnosis. Women diagnosed with breast cancer should be encouraged to initiate and maintain a program of physical activity.
Cancer Prevention Research 04/2011; 4(4):522-9. · 4.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Medication adherence may be a proxy for healthy behaviors and other factors that affect outcomes. Prior studies of the association between placebo adherence and health outcomes have been limited primarily to men enrolled in clinical trials and cardiovascular disease outcomes. We examined associations between adherence to placebo and the risk of fracture, coronary heart disease, cancer, and all-cause mortality in the 2 Women's Health Initiative hormone therapy randomized trials.
Postmenopausal women randomized to placebo with adherence measured at least once were eligible for analysis. Time-varying adherence was assessed by dispensing history and pill counts. Outcome adjudication was based on physician review of medical records. Cox proportional hazards models evaluated the relation between high adherence (≥80%) to placebo and various outcomes, referent to low adherence (<80%).
A total of 13,444 postmenopausal women were under observation for 106,066 person-years. High placebo adherence was inversely associated with most outcomes including hip fracture [hazard ratio (HR), 0.50; 95% confidence interval (CI), 0.33-0.78], myocardial infarction (HR, 0.69; 95% CI, 0.50-0.95), cancer death (HR, 0.60; 95% CI, 0.43-0.82), and all-cause mortality (HR, 0.64; 95% CI, 0.51-0.80) after adjustment for potential confounders. Women with low adherence to placebo were 20% more likely to have low adherence to statins and osteoporosis medications.
In the Women's Health Initiative clinical trials, high adherence to placebo was associated with favorable clinical outcomes and mortality. Until the healthy behaviors and/or other factors for which high adherence is a proxy can be better elucidated, caution is warranted when interpreting the magnitude of benefit of medication adherence.
Medical care 03/2011; 49(5):427-35. · 3.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Results of the Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHI-DM) suggest that a low-fat diet may be associated with beneficial health outcomes for specific groups of women.
The objective is to assess how cost-effective the WHI-DM would be if implemented as a public health intervention and under the sponsorship of private health insurers and Medicare. Breast and ovarian cancers are the health outcomes of interest.
Two groups of WHI-DM participants form the target population for this analysis: participants consuming >36.8% of energy from fat at baseline, and participants at high risk for breast cancer with 32% or more of energy from fat at baseline.
This study uses Markov cohort modeling, following societal and health care payer perspectives, with Monte Carlo simulations and one-way sensitivity analyses. WHI-DM records, nationally representative prices, and published estimates of medical care costs were the sources of cost information. Simulations were performed for hypothetical cohorts of women aged 50, 55, 60, 65, or 70 years at the beginning of the intervention. Effectiveness was estimated by quality-adjusted life years (QALYs) and the main outcome measure was the incremental cost-effectiveness ratio (ICER).
Following the societal perspective, the ICERs for the 50-year old cohort are $13,773/QALY (95% confidence interval $7,482 to $20,916) for women consuming >36.8% of energy from fat at baseline and $10,544/QALY ($2,096 to $23,673) for women at high risk for breast cancer. The comparable ICER from a private health care payer perspective is $66,059/QALY ($30,155 to $121,087) and from a Medicare perspective, it is $15,051/QALY ($6,565 to $25,105).
The WHI-DM is a cost-effective strategy for the prevention of breast and ovarian cancers in the target population, from both societal and Medicare perspectives. Private health care payers have a relative short timeframe to realize a return on investment, since after age 65 years the financial benefits associated with the prevention program would accrue to Medicare. For this reason, the intervention is not cost-effective from a private health care payer perspective.
Journal of the American Dietetic Association 01/2011; 111(1):56-66. · 3.59 Impact Factor
-
Sholom Wacholder,
Patricia Hartge,
Ross Prentice,
Montserrat Garcia-Closas,
Heather Spencer Feigelson,
W Ryan Diver,
Michael J Thun,
David G Cox,
Susan E Hankinson,
Peter Kraft, [......],
Rebecca D Jackson,
Dennis W Buckman,
Peter Hui,
Ruth Pfeiffer,
Kevin B Jacobs,
Gilles D Thomas,
Robert N Hoover,
Mitchell H Gail,
Stephen J Chanock,
David J Hunter
[show abstract]
[hide abstract]
ABSTRACT: Genomewide association studies have identified multiple genetic variants associated with breast cancer. The extent to which these variants add to existing risk-assessment models is unknown.
We used information on traditional risk factors and 10 common genetic variants associated with breast cancer in 5590 case subjects and 5998 control subjects, 50 to 79 years of age, from four U.S. cohort studies and one case-control study from Poland to fit models of the absolute risk of breast cancer. With the use of receiver-operating-characteristic curve analysis, we calculated the area under the curve (AUC) as a measure of discrimination. By definition, random classification of case and control subjects provides an AUC of 50%; perfect classification provides an AUC of 100%. We calculated the fraction of case subjects in quintiles of estimated absolute risk after the addition of genetic variants to the traditional risk model.
The AUC for a risk model with age, study and entry year, and four traditional risk factors was 58.0%; with the addition of 10 genetic variants, the AUC was 61.8%. About half the case subjects (47.2%) were in the same quintile of risk as in a model without genetic variants; 32.5% were in a higher quintile, and 20.4% were in a lower quintile.
The inclusion of newly discovered genetic factors modestly improved the performance of risk models for breast cancer. The level of predicted breast-cancer risk among most women changed little after the addition of currently available genetic information.
New England Journal of Medicine 03/2010; 362(11):986-93. · 53.30 Impact Factor
-
Rowan Chlebowski,
Jack Cuzick,
Dereck Amakye,
Ingo Bauerfeind,
Aman Buzdar,
Stephen Chia,
Bruno Cutuli,
Rick Linforth,
Nicolaì Maass,
Shinzaburo Noguchi,
André Robidoux,
Sunil Verma,
Peyman Hadji
Breast (Edinburgh, Scotland) 09/2009; 18 Suppl 2:S1-11. · 2.09 Impact Factor
-
Bette J Caan,
Aaron Aragaki,
Cynthia A Thomson,
Marcia L Stefanick, Rowan Chlebowski,
F Allan Hubbell,
Lesley Tinker,
Mara Vitolins,
Aleksandar Rajkovic,
Maria Bueche,
Judy Ockene
[show abstract]
[hide abstract]
ABSTRACT: To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms.
Postmenopausal women age 50 to 79 years enrolled onto the Women's Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators.
Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata.
The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.
Journal of Clinical Oncology 09/2009; 27(27):4500-7. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (n = 125) or 60 mg denosumab (n = 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months' treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (P < 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.
Breast Cancer Research and Treatment 04/2009; 118(1):81-7. · 4.43 Impact Factor
-
Hiroyuki Katayama,
Sophie Paczesny,
Ross Prentice,
Aaron Aragaki,
Vitor M Faca,
Sharon J Pitteri,
Qing Zhang,
Hong Wang,
Melissa Silva,
Jacob Kennedy,
Jacques Rossouw,
Rebecca Jackson,
Judith Hsia, Rowan Chlebowski,
Joann Manson,
Samir Hanash
[show abstract]
[hide abstract]
ABSTRACT: ABSTRACT : BACKGROUND : The availability of serum collections from the Women's Health Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial provides an opportunity to test the potential of in-depth quantitative proteomics to uncover changes in the serum proteome related to CEE and to assess their relevance to trial findings, including elevations in the risk of stroke and venous thromboembolism and a reduction in fractures. METHODS : Five independent large scale quantitative proteomics analyses were performed, each comparing a set of pooled serum samples collected from 10 subjects, 1 year following initiation of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that exhibited increased levels with CEE by quantitative proteomics was selected for validation studies. RESULTS : Of 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05. Most of the changed proteins were not previously known to be affected by CEE and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance. To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received CEE. CONCLUSIONS : CEE affected a substantial fraction of the serum proteome, including proteins with relevance to findings from the WHI CEE trial related to cardiovascular disease and fracture. CLINICAL TRIALS REGISTRATION : ClinicalTrials.gov identifier: NCT00000611.
Genome Medicine 04/2009; 1(4):47.
-
Gilles Thomas,
Kevin B Jacobs,
Peter Kraft,
Meredith Yeager,
Sholom Wacholder,
David G Cox,
Susan E Hankinson,
Amy Hutchinson,
Zhaoming Wang,
Kai Yu, [......],
Lars J Vatten,
Kristian Hveem,
Merethe Kumle,
Richard B Hayes,
Margaret Tucker,
Daniela S Gerhard,
Joseph F Fraumeni,
Robert N Hoover,
Stephen J Chanock,
David J Hunter
[show abstract]
[hide abstract]
ABSTRACT: We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433; P = 6.74 x 10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24.1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1.
Nature Genetics 04/2009; 41(5):579-84. · 35.53 Impact Factor
-
Gilles Thomas,
Kevin B Jacobs,
Peter Kraft,
Meredith Yeager,
Sholom Wacholder,
David G Cox,
Susan E Hankinson,
Amy Hutchinson,
Zhaoming Wang,
Kai Yu, [......],
Lars J Vatten,
Kristian Hveem,
Merethe Kumle,
Richard B Hayes,
Margaret Tucker,
Daniela S Gerhard,
Joseph F Fraumeni,
Robert N Hoover,
Stephen J Chanock,
David J Hunter
[show abstract]
[hide abstract]
ABSTRACT: We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433;
Nature Genetics 03/2009; 41(5):579-584. · 35.53 Impact Factor
-
Rowan T Chlebowski
[show abstract]
[hide abstract]
ABSTRACT: After local therapy, women with early breast cancer remain at risk of recurrence for an extended period. For women with hormone-receptor-positive (HR+) disease, the risk of relapse peaks in the first 2-3 years after surgery. Distant metastases, which are associated with a high risk of death from breast cancer, account for the majority of relapses, both early and late. Preventing distant metastases is therefore a primary aim of systemic adjuvant treatment. Tamoxifen was the mainstay of endocrine adjuvant treatment for HR+ disease, but despite its proven benefits, a significant proportion of patients will relapse while on tamoxifen therapy. The third-generation aromatase inhibitors (AIs)--letrozole, anastrozole, and exemestane--have recently replaced tamoxifen as the recommended adjuvant endocrine therapy, on the basis of greater efficacy and better tolerability. However, the optimal use of AIs in the adjuvant setting requires further investigation, including identification of the best treatment strategy. Although a switching strategy does reduce relapses, only upfront AI therapy can address the early peak of distant recurrences that occur despite tamoxifen. Similarly, only upfront AI therapy can avoid the life-threatening side effects that occur in the early years of tamoxifen therapy. Available evidence supports a hypothesis that upfront adjuvant AI therapy is the most appropriate treatment strategy for postmenopausal patients with HR+ disease. Definitive evidence awaits results from ongoing randomized trials.
Breast Cancer Research and Treatment 01/2009; 112 Suppl 1:25-34. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease, a condition which is associated with increased risk of breast cancer. We used the Women's Health Initiative randomized controlled trial. The 36,282 participants were randomized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D(3) (GlaxoSmithKline) twice daily (n = 18,176) or to placebo (n = 18,106). Regular mammograms and clinical breast exams were performed. We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. After an average follow-up period of 6.8 years, 915 incident cases of benign proliferative breast disease had been ascertained, with 450 in the intervention group and 465 in the placebo group. Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall (hazard ratio = 0.99, 95% confidence interval = 0.86-1.13), or by histologic subtype. Risk varied significantly by levels of age at baseline, but not by levels of other variables. Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D(3) for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease.
Breast Cancer Research and Treatment 11/2008; 116(2):339-50. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Adjuvant aromatase inhibitor therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is complicated by accelerated bone loss and increased fracture risk. We investigated the ability of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, to protect against aromatase inhibitor-induced bone loss.
Eligible women with hormone receptor-positive nonmetastatic breast cancer treated with adjuvant aromatase inhibitor therapy were stratified by duration of aromatase inhibitor therapy (< or = 6 v > 6 months), received supplemental calcium and vitamin D, and were randomly assigned to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n = 127) every 6 months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary end point was percentage change from baseline at month 12 in lumbar spine bone mineral density (BMD).
At 12 and 24 months, lumbar spine BMD increased by 5.5% and 7.6%, respectively, in the denosumab group versus placebo (P < .0001 at both time points). Increases were observed as early as 1 month and were not influenced by duration of aromatase inhibitor therapy. Increases in BMD were also observed at the total hip, total body, femoral neck, and the predominantly cortical one-third radius. Bone turnover markers decreased with denosumab treatment. Overall incidence of treatment-emergent adverse events (AEs) was similar between treatment groups.
In women with nonmetastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy, twice-yearly administration of denosumab led to significant increases in BMD over 24 months at trabecular and cortical bone, with overall AE rates similar to those of placebo.
Journal of Clinical Oncology 09/2008; 26(30):4875-82. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Gail model has been commonly used to estimate a woman's risk of breast cancer within a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it appears to play no role in the Gail model. The objective of the current study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score.
In this prospective study, 9941 postmenopausal women who had a baseline hip BMD and Gail score from the Women's Health Initiative were included in the analysis. Their average age was 63.0 +/- 7.4 years at baseline.
After an average of 8.43 years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazards ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (>or=1.67%) and 1.25 (95% CI, 1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting the analysis to women with both BMD and a Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (P < .05).
The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population was found to be independent of the Gail score. However, among women with both high BMD and a high Gail score, there appears to be an interaction between these 2 factors. These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer.
Cancer 09/2008; 113(5):907-15. · 4.77 Impact Factor
-
Rowan Chlebowski
Journal of Nutrition 02/2007; 137(1 Suppl):233S-235S. · 3.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones.
Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone-binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial.
In multiple regression analyses on log-transformed hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001), estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001), free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p = 0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (beta = -0.006, -0.007, and -0.005, respectively, all p < or = 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend < 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG.
These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.
Obesity 10/2006; 14(9):1662-77. · 4.28 Impact Factor
