49 results on '"Kathy Pan"'
Search Results
2. Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women’s Health Initiative
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Christina M. Dieli-Conwright, Rebecca A. Nelson, Michael S. Simon, Melinda L. Irwin, Marian L. Neuhouser, Kerryn W. Reding, Tracy E. Crane, JoAnn E. Manson, Rami Nassir, Aladdin H. Shadyab, Michael LaMonte, Lihing Qi, Cynthia A. Thomson, Candyce H. Kroenke, Kathy Pan, Rowan T. Chlebowski, and Joanne Mortimer
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Physical activity ,Metabolic syndrome ,Breast cancer ,Gynecology and obstetrics ,RG1-991 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown. Methods Cardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women’s Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group. Results Among 161,308 Women’s Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78–0.95, trend P
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- 2022
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3. Adiposity and breast, endometrial, and colorectal cancer risk in postmenopausal women: Quantification of the mediating effects of leptin, C‐reactive protein, fasting insulin, and estradiol
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S. Ghazaleh Dashti, Julie A. Simpson, Vivian Viallon, Amalia Karahalios, Margarita Moreno‐Betancur, Theodore Brasky, Kathy Pan, Thomas E. Rohan, Aladdin H. Shadyab, Cynthia A. Thomson, Robert A. Wild, Sylvia Wassertheil‐Smoller, Gloria Y. F. Ho, Howard D. Strickler, Dallas R. English, and Marc J. Gunter
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breast cancer ,causal mediation analysis ,colorectal cancer ,endometrial cancer ,estrogens ,inflammation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Mechanisms underlying the adiposity–cancer relationship are incompletely understood. We quantified the mediating roles of C‐reactive protein (CRP), leptin, fasting insulin, and estradiol in the effect of adiposity on estrogen receptor (ER)‐positive breast, endometrial, and colorectal cancer risk in postmenopausal women. Methods We used a case–cohort study within the Women's Health Initiative Observational Study, analyzed as a cumulative sampling case–control study. The study included 188 breast cancer cases, 98 endometrial cancer cases, 193 colorectal cancer cases, and 285 controls. Interventional indirect and direct effects on the risk ratio (RR) scale were estimated using causal mediation analysis. Results For breast cancer, the total effect RR for BMI ≥30 versus ≥18.5–
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- 2022
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4. The association between DXA‐derived body fat measures and breast cancer risk among postmenopausal women in the Women's Health Initiative
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Rhonda S. Arthur, Xiaonan Xue, Victor Kamensky, Rowan T. Chlebowski, Michael Simon, Juhua Luo, Aladdin H. Shadyab, Marian L. Neuhouser, Hailey Banack, Gloria Y. F. Ho, Dorothy S. Lane, Kathy Pan, Kerryn W. Reding, Sylvia Wassertheil‐Smoller, Andrew J. Dannenberg, and Thomas E. Rohan
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body fat ,breast cancer risk ,postmenopausal women ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Most studies demonstrating an association between excess adiposity and postmenopausal breast cancer have used anthropometric measures, particularly body mass index (BMI). However, more direct body fat measures may more accurately determine the relationship between body fat distribution and breast cancer risk. Methods Cox proportional hazards regression models were created to examine the associations of dual‐energy x‐ray absorptiometry (DXA) body fat measures (at baseline and during follow‐up) with breast cancer risk among 10 931 postmenopausal women from the Women's Health Initiative cohort. A total of 639 incident invasive breast cancer cases (including 484 estrogen receptor positive (ER+) cases) were ascertained after a median follow‐up of 15.0 years. Results Excess whole body fat mass and trunk fat mass were positively associated with risk invasive breast cancer risk. These associations persisted even after additional adjustment for standard anthropometric measures. In time‐dependent analyses, we observed that both whole body fat mass and trunk fat mass, in the highest versus lowest category, were associated with a doubling of risk of invasive breast cancer overall (HR: 2.17; 95% CI: 1.54‐3.05 and 2.20; 1.55‐3.14, respectively) and of ER+ breast cancer (2.05; 1.37‐3.05 and 2.03; 1.34‐3.07, respectively). The remaining DXA measures were also positively associated with breast cancer risk in baseline and time‐dependent analyses. Conclusion These findings suggest that DXA‐derived body fat measures are positively associated with breast cancer risk after adjustment for BMI and other conventional breast cancer risk factors.
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- 2020
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5. Low-fat dietary pattern and global cognitive function: Exploratory analyses of the Women's Health Initiative (WHI) randomized Dietary Modification trial
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Rowan T. Chlebowski, Steve Rapp, Aaron K. Aragaki, Kathy Pan, Marian L. Neuhouser, Linda G. Snetselaar, JoAnn E. Manson, Jean Wactawski-Wende, Karen C. Johnson, Kathleen Hayden, Laura D. Baker, Victor W. Henderson, Lorena Garcia, Lihong Qi, and Ross L. Prentice
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Medicine (General) ,R5-920 - Abstract
Background: Meta-analyses of observational studies associate adherence to several dietary patterns with cognitive health. However, limited evidence from full scale, randomized controlled trials precludes causal inference regarding dietary effects on cognitive function. Methods: The Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, in 48,835 postmenopausal women, included a subset of 1,606 WHI Memory Study (WHIMS) participants >= 65 years old, to assess low-fat dietary pattern influence on global cognitive function, evaluated with annual screening (Modified Mini–Mental State Examinations [3MSE]). Participants were randomized by a computerized, permuted block algorithm, stratified by age group and center, to a dietary intervention (40%) to reduce fat intake to 20% of energy and increase fruit, vegetable and grain intake or usual diet comparison groups (60%). The study outcome was possible cognition impairment (failed cognitive function screening) through the 8.5 year (median) dietary intervention. Those failing screening received a comprehensive, multi-phase cognitive function assessment to classify as: no cognitive impairment, mild cognitive impairment, or probable dementia. Exploratory analyses examined the composite endpoint of death after possible cognitive impairment through 18.7 years (median) follow-up. The WHI trials are registered at ClinicalTrials.gov:NCT00000611. Findings: Among the 1,606 WHIMS participants, the dietary intervention statistically significantly reduced the incidence of possible cognitive impairment (n = 126; hazard ratio [HR] 0.59 95% confidence interval [CI] 0.38–0. 91, P = 0.01) with HR for dietary influence on subsequent mild cognitive impairment of 0.65 (95% CI 0.35–1.19) and HR of 0.63 (95% CI 0.19–2.10) for probable dementia (PD). Through 18.7 years, deaths from all-causes after possible cognitive impairment were non-significantly lower in the dietary intervention group (0.56% vs 0.77%, HR 0.83 95% CI 0.35 to 2.00, P = 0.16). Interpretation: Adoption of a low-fat eating pattern, representing dietary moderation, significantly reduced risk of possible cognitive impairment in postmenopausal women. Funding: Several Institutes of the US National Institutes of Health. Keywords: Cognition, Dietary modification, Low-fat dietary pattern, Randomized clinical trial, Women's Health Initiative
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- 2020
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6. Frequency of Consuming Breakfast Meals and After-Dinner Snacks Is not Associated with Postmenopausal Breast Cancer Risk: Women’s Health Initiative Observational Study
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Valeria Elahy, Cynthia Thomson, Marian L. Neuhouser, Luohua Jiang, Sunmin Lee, Kathy Pan, Mara Vitolins, Rowan Chlebowski, Dorothy Lane, and Andrew O. Odegaard
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Nutrition and Dietetics ,Medicine (miscellaneous) - Published
- 2023
7. Neighborhood Socioeconomic Status, Green Space, and Walkability and Risk for Falls Among Postmenopausal Women: The Women's Health Initiative
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Marilyn E. Wende, Matthew C. Lohman, Daniela B. Friedman, Alexander C. McLain, Michael J. LaMonte, Eric A. Whitsel, Aladdin H. Shadyab, Lorena Garcia, Benjamin W. Chrisinger, Kathy Pan, Chloe E. Bird, Gloria E. Sarto, and Andrew T. Kaczynski
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Aging ,Health (social science) ,Rehabilitation ,Public Health, Environmental and Occupational Health ,Obstetrics and Gynecology ,Walking ,Postmenopause ,Paediatrics and Reproductive Medicine ,Social Class ,Residence Characteristics ,Clinical Research ,Maternity and Midwifery ,Behavioral and Social Science ,Public Health and Health Services ,Humans ,Women's Health ,Female ,Public Health - Abstract
PurposeThis study estimated associations between neighborhood socioeconomic status (NSES), walkability, green space, and incident falls among postmenopausal women and evaluated modifiers of these associations, including study arm, race and ethnicity, baseline household income, baseline walking, age at enrollment, baseline low physical functioning, baseline fall history, climate region, and urban-rural residence.MethodsThe Women's Health Initiative recruited a national sample of postmenopausal women (50-79years) across 40 U.S. clinical centers and conducted yearly assessments from 1993 to 2005 (n=161,808). Women reporting a history of hip fracture or walking limitations were excluded, yielding a final sample of 157,583 participants. Falling was reported annually. NSES (income/wealth, education, occupation), walkability (population density, diversity of land cover, nearby high-traffic roadways), and green space (exposure to vegetation) were calculated annually and categorized into tertiles (low, intermediate, high). Generalized estimating equations assessed longitudinal relationships.ResultsNSES was associated with falling before adjustment (high vs. low, odds ratio,1.01; 95% confidence interval, 1.00-1.01). Walkability was significantly associated with falls after adjustment (high vs. low, odds ratio,0.99; 95% confidence interval, 0.98-0.99). Green space was not associated with falling before or after adjustment. Study arm, race and ethnicity, household income, age, low physical functioning, fall history, and climate region modified the relationship between NSES and falling. Race and ethnicity, age, fall history, and climate region modified relationships between walkability and green space and falling.ConclusionsOur results did not show strong associations of NSES, walkability, or green space with falling. Future research should incorporate granular environmental measures that may directly relate to physical activity and outdoor engagement.
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- 2023
8. Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies
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Yumie Takata, Jae Jeong Yang, Danxia Yu, Stephanie A. Smith-Warner, William J. Blot, Emily White, Kimberly Robien, Anna Prizment, Kana Wu, Norie Sawada, Qing Lan, Yikyung Park, Yu-Tang Gao, Qiuyin Cai, Mingyang Song, Xuehong Zhang, Kathy Pan, Antonio Agudo, Salvatore Panico, Linda M. Liao, Shoichiro Tsugane, Rowan T. Chlebowski, Therese Haugdahl Nøst, Matthias B. Schulze, Mattias Johannson, Wei Zheng, and Xiao-Ou Shu
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Nutrition and Dietetics ,Medicine (miscellaneous) - Published
- 2023
9. Association between baseline insulin resistance and psoriasis incidence: the Women’s Health Initiative
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Wendy Li, Kathy Pan, Houmin Li, Delphine J. Lee, Rowan T. Chlebowski, Jennifer K. Yee, and Alfred A. Chan
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medicine.medical_specialty ,Dermatology ,Medicare ,Cohort Studies ,Insulin resistance ,Risk Factors ,Internal medicine ,Psoriasis ,medicine ,Humans ,Insulin ,Aged ,business.industry ,Proportional hazards model ,Incidence ,Incidence (epidemiology) ,Women's Health Initiative ,General Medicine ,medicine.disease ,United States ,Clinical trial ,Cohort ,Women's Health ,Female ,Diagnosis code ,Insulin Resistance ,business - Abstract
Small-scale studies offer conflicting evidence regarding the relationship/association between psoriasis and insulin resistance by HOMA-IR (homeostasis model assessment of insulin resistance). The purpose of this study was to assess the association between baseline HOMA-IR and psoriasis incidence in a large-scale longitudinal cohort of postmenopausal women. The analysis included 21,789 postmenopausal women from the Women’s Health Initiative. Psoriasis diagnosis was defined by fee-for-service Medicare ICD-9-CM codes assigned by dermatologists or rheumatologists, and a 2-year lookback period to exclude prevalent cases. Baseline HOMA-IR was calculated using the updated HOMA2 model. Hazard rates from the Cox regression models were stratified by age (10-year intervals), on WHI component (Clinical Trial or Observational Study), and on randomization status within each of the WHI clinical trials. The complete model also adjusted for ethnicity, waist–hip-ratio, and smoking and alcohol habits. Among participants free of psoriasis at entry, those with high baseline HOMA-IR (≥ 2) compared to low (P-trend: 0.011). In postmenopausal women, higher baseline HOMA-IR levels were significantly associated with higher incidence of psoriasis over 21-year cumulative follow-up. Results from this time-to-event analysis indicate that insulin resistance can precede and is associated with an increased risk of psoriasis. Study is limited by Medicare diagnostic code accuracy and cohort age.
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- 2021
10. Social Support, social ties, and cognitive function of women with breast cancer: findings from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study
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Yesol Yang, Eric M. McLaughlin, Michelle J. Naughton, Maryam B. Lustberg, Timiya S. Nolan, Candyce H. Kroenke, Julie C. Weitlauf, Nazmus Saquib, Aladdin H. Shadyab, Shawna Follis, Kathy Pan, and Electra D. Paskett
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Oncology - Abstract
Purpose This study examined associations between self-reported cognitive functioning and social support as well as social ties among women with breast cancer. Methods The study included 3351 women from the Women’s Health Initiative Life and Longevity After Cancer cohort who were diagnosed with breast cancer stages I–III. Social support was assessed using a modified Medical Outcomes Study (MOS) Social Support Survey, and marital status was obtained from the baseline questionnaire. We also assessed social ties (e.g., number of friends, relatives, living children) and cognitive function (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-COG]) on the year-1-follow up questionnaire. Multivariable quantile regression was used to estimate the changes in median cognitive scores. Kruskal–Wallis tests were used to assess the association of cognitive function with social ties. Results The majority of participants were non-Hispanic White (93.3%), presently married (49%), with at least a 4-year college degree (53.2%), and had been diagnosed with localized breast cancer (79%). A 10-point higher social support score correlated to a 0.32 higher (better) median cognitive score (p p = 0.01). Significant associations were also present for having close relatives (p p Conclusion Women reporting higher social support and greater numbers of friends or relatives have higher cognitive functioning. Compared to divorced or separated women, married women were likely to have higher cognitive functioning. These findings suggest that social support assessments have the potential to help identify women at higher risk of cognitive decline.
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- 2022
11. Low-Fat Dietary Modification and Risk of Ductal Carcinoma In Situ of the Breast in the Women's Health Initiative Dietary Modification Trial
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Fred K. Tabung, JoAnn E. Manson, Aladdin H. Shadyab, Dorothy S. Lane, Sylvia Wassertheil-Smoller, Tracy E. Crane, Rowan T. Chlebowski, Rita Peila, Ana Barac, Zhenzhen Zhang, Kathy Pan, Thomas E. Rohan, and Nazmus Saquib
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Oncology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Proportional hazards model ,Women's Health Initiative ,Ductal carcinoma ,medicine.disease ,Confidence interval ,law.invention ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Observational study ,Total energy ,skin and connective tissue diseases ,business - Abstract
Background: Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinoma in situ (DCIS) of the breast, a putative breast cancer precursor, has not been reported. Methods: A total of 48,835 postmenopausal women, ages 50–79 years at enrollment, with no breast cancer history and ≥32% of total energy intake from fat, were randomly assigned either to a dietary intervention (n = 19,541) designed to reduce total fat intake to 20% of energy and to increase vegetable, fruit, and grain consumption, or to a comparison group (n = 29,294). Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the association between the intervention and DCIS risk. Results: During 18.7 years (median) cumulative follow-up, including intervention (∼8.7 years) and post-intervention phases (∼13.0 years), 817 DCIS cases were ascertained. No evidence of an association between the DM intervention and DCIS risk was observed overall, or by trial phase (intervention and post-intervention). Similarly, no associations were found in subgroups defined by potential risk factors for DCIS. Conclusions: DM aiming to reduce fat intake was not associated with altered risk of DCIS. Impact: These results do not provide evidence of an association between dietary fat reduction and the risk of DCIS among postmenopausal women.
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- 2021
12. Temporal Associations and Outcomes of Breast Cancer and Heart Failure in Postmenopausal Women
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Charles B. Eaton, Selma F. Mohammed, Kathy Pan, Helen Sheriff, Barbara V. Howard, Liviu Klein, Gregg C. Fonarow, Samer S. Najjar, Phillip H. Lam, Charity J. Morgan, Ana Barac, Kerryn W. Reding, Rowan T. Chlebowski, Ali Ahmed, and Anju Nohria
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medicine.medical_specialty ,BMI, body mass index ,heart failure ,HF, heart failure ,Breast cancer ,breast cancer ,Internal medicine ,medicine ,skin and connective tissue diseases ,Original Research ,Postmenopausal women ,business.industry ,Incidence (epidemiology) ,HF - Heart failure ,medicine.disease ,mortality ,HR, hazard ratio ,CI, confidence interval ,Oncology ,Heart failure ,incidence ,Cardiology and Cardiovascular Medicine ,business ,WHI, Women’s Health Initiative ,BMI - Body mass index ,WHR, waist-hip ratio - Abstract
Background Heart failure (HF) and breast cancer are 2 of the leading causes of death in postmenopausal women. The temporal association between HF and breast cancer in postmenopausal women has not been described. Objectives This study sought to examine the temporal association between HF and breast cancer. Methods Postmenopausal women within the WHI (Women’s Health Initiative) cohort were studied. All prevalent HF and prevalent breast cancer at enrollment were self-reported. Incident hospitalized HF and breast cancer diagnoses were adjudicated through 2017. Results Among a cohort of 44,174 women (mean age 63 ± 7 years), 2,188 developed incident invasive breast cancer and 2,416 developed incident hospitalized HF over a median follow-up of 14 and 15 years, respectively. When compared with a breast cancer- and HF-free cohort, there was no association between prevalent HF and incident invasive breast cancer and similarly, there was no association between prevalent breast cancer and incident hospitalized HF. Across the entire cohort, the median survival after incident hospitalized HF was worse compared with an incident invasive breast cancer diagnosis (5 and 19 years, respectively). In women with incident invasive breast cancer, prevalent HF was associated with an increased risk of mortality (hazard ratio: 2.28; 95% confidence interval: 1.31 to 3.95). In women with incident hospitalized HF, prevalent breast cancer was associated with an increased risk of mortality (hazard ratio: 1.66; 95% confidence interval: 1.03 to 2.68). Cause of death after incident HF was different only in women with prevalent and interim breast cancer compared with those without prevalent and interim breast cancer. Conclusions In postmenopausal women, prevalent HF was not associated with a higher incidence of breast cancer and vice versa. However, the presence of incident invasive breast cancer or incident HF in those with prevalent HF or prevalent breast cancer, respectively, was associated with increased mortality., Central Illustration
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- 2020
13. Association of Diet Quality and Physical Activity on Obesity-Related Cancer Risk and Mortality in Black Women: Results from the Women's Health Initiative
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Joy J. Chebet, JoAnn E. Manson, Rowan T. Chlebowski, Kathy Pan, Juhua Luo, John E. Ehiri, Tongguang Cheng, Nazmus Saquib, Lindsay N. Kohler, Cynthia A. Thomson, Melanie L. Bell, Shawnita Sealy-Jefferson, and Rami Nassir
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0301 basic medicine ,Epidemiology ,Risk Assessment ,Metabolic equivalent ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Neoplasms ,medicine ,Humans ,Obesity ,Prospective Studies ,Mortality ,Prospective cohort study ,Exercise ,Life Style ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Incidence ,Women's Health Initiative ,Cancer ,Feeding Behavior ,Health Status Disparities ,Middle Aged ,medicine.disease ,United States ,Confidence interval ,Black or African American ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Body mass index ,Follow-Up Studies ,Demography - Abstract
Background: Obesity-related cancers disproportionately affect the Black community. We assessed the relationship between diet quality, physical activity, and their combined effect on obesity-related cancer risk and mortality in Black women enrolled in the Women's Health Initiative (WHI). Methods: Data from postmenopausal (50–79 years of age) Black women enrolled in WHI clinical trials or observational studies were analyzed. Exposure variables included baseline physical activity [metabolic equivalent of tasks (MET)-hours/week of moderate-to-vigorous physical activity (MVPA)] and diet quality [Healthy Eating Index (HEI)-2015]. Outcomes included adjudicated obesity-related cancer incidence and mortality. Cox proportional hazard models were used to evaluate the association between MVPA and HEI-2015 and obesity-related cancer risk and mortality. Results: The analytical sample included 9,886 Black women, with a baseline mean body mass index (BMI) of 31.1 kg/m2 (SD = 6.8); mean HEI-2015 score of 63.2 (SD = 11.0, possible range 0 to 100); and mean MVPA of 5.0 (SD = 9.4) MET-hours/week. Over an average of 13 years of follow-up, 950 (9.6%) obesity-related cancer cases were observed, with 313 (32.9%) resulting in death. Physical activity [HR, 1.05; 95% confidence interval (CI), 0.86–1.30], diet quality (HR, 0.99; 95% CI, 0.92–1.08), and their combination (HR, 1.05; 95% CI, 0.85–1.29) were not associated with risk for any or site-specific obesity-related cancers. Similarly, these health behaviors had no association with mortality. Conclusions: Diet quality, physical activity and their combined effect, as measured, were not associated with obesity-related cancer risk and mortality in Black women enrolled in WHI. Impact: Other social, behavioral, and biological factors may contribute to racial disparities observed in obesity-related cancer rates.
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- 2020
14. The association of delay in curative intent treatment with survival among breast cancer patients: findings from the Women’s Health Initiative
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Wendy E. Barrington, Kathy Pan, Greg S. Warnick, Candyce H. Kroenke, Chunkit Fung, Michael S. Simon, Di Wang, Roberta M. Ray, Garnet L. Anderson, Lisa Johnson, Rachel L. Yung, Joshua A. Roth, Kerryn W. Reding, and Rowan T. Chlebowski
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Article ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,medicine ,Humans ,Initial treatment ,Prospective Studies ,Stage (cooking) ,Aged ,Aged, 80 and over ,Curative intent ,Prior treatment ,Chemotherapy ,business.industry ,Proportional hazards model ,Women's Health Initiative ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Survival Rate ,030104 developmental biology ,Receptors, Estrogen ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,Receptors, Progesterone ,business ,Follow-Up Studies - Abstract
PURPOSE: Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. METHODS: We included 3368 women with incident stage I-III BC in the Women’s Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as >8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. RESULTS: We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR=1.71; 95% CI: 1.07–2.75) and ACM (HR=1.39; 95% CI: 1.02–1.90); delay in radiation increased BCSM risk (HR=1.49; 95% CI: 1.00–2.21) but not ACM risk (HR=1.19; 95% CI: 0.99–1.42). Delays across multiple treatment modalities increased BCSM risk 3-fold (95% CI: 1.51–6.12) and ACM risk 2.3-fold (95% CI: 1.50–3.50). CONCLUSIONS: A delay to a single treatment modality, and to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.
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- 2020
15. Abstract P5-12-04: Association of adjuvant endocrine therapy with diabetes among women with postmenopausal breast cancer in the Women’s Health Initiative (WHI)
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Barbara V. Howard, Joanne E. Mortimer, Lewis H. Kuller, Christina M Dieli Conwright, Kathy Pan, Rebecca A. Nelson, Aladdin H. Shadyab, Laura Kruper, and Rowan T. Chlebowski
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Cancer Research ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,Women's Health Initiative ,Hazard ratio ,Cancer ,medicine.disease ,Breast cancer ,Oncology ,Internal medicine ,medicine ,Hormone therapy ,business ,Adverse effect ,Tamoxifen ,medicine.drug - Abstract
Background: In postmenopausal women, use of hormone therapy is associated with a lower incidence of diabetes (DM). The association of adjuvant endocrine therapy (AET) with DM has not been well studied among women treated for early stage breast cancer. The objective of this study was to examine the association of AET with risk of developing DM among postmenopausal women who developed breast cancer. Methods: 5,013 postmenopausal women from the Women’s Health Initiative diagnosed with non-metastatic breast cancer who were diabetes-free at cancer diagnosis and who had information on use of AET were included. AET use was gathered using 2 methods: 1) review of medication inventories for use of tamoxifen or aromatase inhibitors (AI) and 2) review of the Life and Longevity after Cancer (LILAC), a supplemental questionnaire used from 2009-2010 to gather treatment information from women who developed cancer. Results from these 2 collection methods were analyzed separately due to the timing of the surveys as well as data granularity (i.e. LILAC queried use of AET, not type). The primary outcome of interest for this study was diabetes-free survival, which was calculated from the date of breast cancer diagnosis to first diagnosis of DM. Participants who did not develop DM after breast cancer were censored at their last follow-up visit or date of death. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: After 10.4 median year’s follow-up post breast cancer diagnosis, 13% (632/5,013) of participants developed DM. Of the 2,646 who had medication inventory data, 1,352 (51%) reported AI use and 1,449 (55%) reported tamoxifen use. Participants who reported use of AIs were 13% more likely to develop DM than participants who did not use AIs (HR=1.13, CI=0.91-1.39). Participants who reported use of tamoxifen were 11% less likely to develop DM than those who did not use tamoxifen (HR=0.89, CI=0.72-1.11). Of the 3,769 participants with LILAC data from the supplemental questionnaire, 2,543 (67%) reported use of AET; these participants were 25% more likely to develop DM than those who did not use AET (HR=1.25, CI=1.02-1.53). When plotted over time, the risk of diabetes in AET users versus non-users was identical at 5 years (5% v 5%, respectively), was 35% higher at 10 years (12% v 9%, respectively), and 30% higher at 15 years (18% v 14%, respectively) (log-rank p=0.029). Conclusion: DM has not been reported as an adverse event in women on AET. Our data suggest an association of AET with DM among postmenopausal women with early stage breast cancer. When looking at specific types of AETs, the risk was marginally increased for AIs but marginally decreased for tamoxifen, with risk more apparent in subsequent years. These data have significance for survivorship care. Citation Format: Joanne E Mortimer, Rebecca A Nelson, Laura Kruper, Kathy Pan, Christina M Dieli Conwright, Aladdin H Shadyab, Lewis Kuller, Barbara Howard, Rowan T Chlebowski. Association of adjuvant endocrine therapy with diabetes among women with postmenopausal breast cancer in the Women’s Health Initiative (WHI) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-04.
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- 2020
16. The association between DXA‐derived body fat measures and breast cancer risk among postmenopausal women in the Women's Health Initiative
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Kathy Pan, Juhua Luo, Victor Kamensky, Rhonda Arthur, Gloria Y.F. Ho, Dorothy S. Lane, Marian L. Neuhouser, Kerryn W. Reding, Andrew J. Dannenberg, Rowan T. Chlebowski, Thomas E. Rohan, Aladdin H. Shadyab, Sylvia Wassertheil-Smoller, Xiaonan Xue, Hailey R. Banack, and Michael S. Simon
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Estrogen receptor ,postmenopausal women ,Breast Neoplasms ,Risk Assessment ,lcsh:RC254-282 ,Body Mass Index ,03 medical and health sciences ,breast cancer risk ,0302 clinical medicine ,Breast cancer ,Absorptiometry, Photon ,Risk Factors ,Internal medicine ,Cox proportional hazards regression ,medicine ,Odds Ratio ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoplasm Invasiveness ,Breast ,Adiposity ,Original Research ,Postmenopausal women ,business.industry ,Women's Health Initiative ,Incidence ,Anthropometry ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,United States ,Postmenopause ,body fat ,030104 developmental biology ,Adipose Tissue ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Body mass index ,Cancer Prevention ,Follow-Up Studies - Abstract
Background Most studies demonstrating an association between excess adiposity and postmenopausal breast cancer have used anthropometric measures, particularly body mass index (BMI). However, more direct body fat measures may more accurately determine the relationship between body fat distribution and breast cancer risk. Methods Cox proportional hazards regression models were created to examine the associations of dual‐energy x‐ray absorptiometry (DXA) body fat measures (at baseline and during follow‐up) with breast cancer risk among 10 931 postmenopausal women from the Women's Health Initiative cohort. A total of 639 incident invasive breast cancer cases (including 484 estrogen receptor positive (ER+) cases) were ascertained after a median follow‐up of 15.0 years. Results Excess whole body fat mass and trunk fat mass were positively associated with risk invasive breast cancer risk. These associations persisted even after additional adjustment for standard anthropometric measures. In time‐dependent analyses, we observed that both whole body fat mass and trunk fat mass, in the highest versus lowest category, were associated with a doubling of risk of invasive breast cancer overall (HR: 2.17; 95% CI: 1.54‐3.05 and 2.20; 1.55‐3.14, respectively) and of ER+ breast cancer (2.05; 1.37‐3.05 and 2.03; 1.34‐3.07, respectively). The remaining DXA measures were also positively associated with breast cancer risk in baseline and time‐dependent analyses. Conclusion These findings suggest that DXA‐derived body fat measures are positively associated with breast cancer risk after adjustment for BMI and other conventional breast cancer risk factors., Our study demonstrated that DXA‐derived body fat measures were positively associated with breast cancer risk after adjustment for BMI and other conventional breast cancer risk factors. These findings suggest that DXA‐derived measures of overall and central adiposity may explain invasive breast cancer risk beyond that of BMI and other risk factors.
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- 2020
17. Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women's Health Initiative Randomized Clinical Trials
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Garnet L. Anderson, Rowan T. Chlebowski, Michael S. Simon, Jane A. Cauley, JoAnn E. Manson, Thomas E. Rohan, Wendy E. Barrington, Lewis H. Kuller, Kathy Pan, Margery Gass, Marcia L. Stefanick, Maryam Sattari, Dorothy S. Lane, Ross L. Prentice, Karen C. Johnson, Electra D. Paskett, and Aaron K. Aragaki
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medicine.medical_specialty ,Hysterectomy ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Mortality rate ,Women's Health Initiative ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,law.invention ,Clinical trial ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Medroxyprogesterone acetate ,business ,medicine.drug - Abstract
Importance The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. Objective To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women’s Health Initiative clinical trials. Design, Setting, and Participants Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27 347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. Interventions In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years’ median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years’ median intervention duration. Main Outcomes and Measures The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. Results Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93;P = .005) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97;P = .04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45;P Conclusions and Relevance In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality.
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- 2020
18. Breast Cancer Prevention: Time for Change
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Rowan T. Chlebowski, Kathy Pan, and Aaron K. Aragaki
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Oncology ,medicine.medical_specialty ,medicine.drug_class ,Estrogen receptor ,Breast Neoplasms ,Risk Assessment ,law.invention ,Clinical Reviews ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,medicine ,Humans ,Raloxifene ,030212 general & internal medicine ,Aromatase ,skin and connective tissue diseases ,biology ,Oncology (nursing) ,business.industry ,Health Policy ,Hazard ratio ,medicine.disease ,Estrogen ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,Tamoxifen ,medicine.drug - Abstract
Agency breast cancer prevention guidelines for other than hereditary cancers have not materially changed in 20 years; endocrine-targeted agents (then, tamoxifen; now, adding raloxifene and aromatase inhibitors) reduce good prognosis estrogen receptor (ER)–positive, progesterone receptor (PR)–positive cancers without reducing deaths from breast cancer. Across three tamoxifen placebo-controlled prevention trials (N = 23,360) begun almost 30 years ago, although there were 226 fewer breast cancer cases, there were nine more deaths from breast cancer in the tamoxifen groups. Following clinical advances, currently more than half of breast cancer cases are solved problems with extremely low risk of death. As endocrine-targeted agents commonly prevent these cancers, widespread implementation of current prevention strategies may not reduce deaths from breast cancer. Compared with other breast cancers, ER-positive, PR-negative cancers and triple-negative cancers have inferior survival (90.6% v 83.8% v 78.1%, respectively; P < .001). Against this background, in the Women's Health Initiative Dietary Modification randomized trial (N = 48,835), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.77; 95% CI, 0.64 to 0.94) and deaths from breast cancer were reduced 21% ( P = .02). In the Women's Health Initiative randomized, placebo-controlled trial evaluating conjugated equine estrogen (N = 10,739), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.44; 95% CI, 0.27 to 0.74) and deaths from breast cancer were reduced 40% ( P = .04). These findings suggest that reexamination of breast cancer risk reduction strategies and clinical practice is needed.
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- 2021
19. African Ancestry and Triple-Negative Breast Cancer in the Women’s Health Initiative
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Rowan T. Chlebowski, Joanne E. Mortimer, Kathy Pan, Rebecca A. Nelson, Veronica Jones, Laura Kruper, and Ramir Nassir
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medicine.medical_specialty ,business.industry ,Women's Health Initiative ,MEDLINE ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,General Medicine ,White People ,Article ,Family medicine ,medicine ,Humans ,Women's Health ,Female ,business ,Triple-negative breast cancer - Abstract
BACKGROUND: Breast cancer mortality is substantially higher in Black compared to White women due in part to higher rates of poor prognosis triple-negative breast cancer (TNBC) in Black women. The influence of African ancestry on this disparity has not been adequately examined. METHODS: Using the Women’s Health Initiative cohort of 161,808 postmenopausal women, we examined risk of TNBC in 6,166 Black participants with information on African ancestry, of whom 374 had incident localized breast cancers. African ancestry was based on genetic information from 656,852 single nucleotide polymorphisms with ancestry groups stratified by
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- 2020
20. Abstract P5-07-03: Metabolic syndrome impacts survival in postmenopausal women with triple negative breast cancer: Results from the women’s health initiative
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Susan E. Yost, Rowan T. Chlebowski, Kathy Pan, Yuan Yuan, Rebecca A. Nelson, Jessica Yan, and Rami Nassir
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Medical record ,Women's Health Initiative ,Cancer ,medicine.disease ,National Death Index ,Breast cancer ,Internal medicine ,Diabetes mellitus ,medicine ,Metabolic syndrome ,business ,Triple-negative breast cancer - Abstract
INTRODUCTION: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer associated with poor clinical outcome. Patients diagnosed with TNBC may experience many treatment-associated changes, including weight gain, reduced physical activity levels, and worsening metabolic profiles. We sought to identify the association between baseline metabolic syndrome (MetS) components with survival outcomes in WHI participants diagnosed with TNBC. METHODS: The WHI comprises 161,308 post-menopausal women aged 50-79 who were enrolled from 1993-1998 and were at low risk of 3-year mortality at study screening. After excluding women with a history of cancer and those randomized to the dietary modification treatment arm, we identified 615 participants diagnosed with non-metastatic TNBC while on study. MetS status at baseline was assessed at study entry (prior to subsequent breast cancer diagnosis) using the following risk factors: 1) high waist circumference (≥88 cm), 2) high blood pressure (>135 mg Hg systolic and/or > 85 diastolic, or anti-hypertension medication use), 3) history of high cholesterol, and 4) history of diabetes. Groups were stratified into: 1) no MetS components (none), 2) 1-2 MetS components, and 3) 3-4 MetS components. All breast cancers were verified by medical record review. Survival status was augmented by serial National Death Index queries. Outcomes of interest included breast cancer specific survival, as well as all-cause survival after breast cancer, with survival time calculated from date of TNBC diagnosis to date of death or off-study. Baseline demographic, clinicopathologic, and treatment differences were assessed across MetS groups using chi-squared analyses. Kaplan-Meier curves were plotted across MetS groups and survival rates were compared using the log-rank statistic. RESULTS: Of 615 participants diagnosed with TNBC, the distribution of MetS was as follows: 29% had no MetS components (n=178), 53% had 1-2 components (n=323), and 7% had 3-4 components (n=43). The median time from enrollment to TNBC diagnosis was 8.6 years (median), with those in the highest MetS group having a significantly shorter time to diagnosis than those without any MetS (7.0 years vs. 9.8 years, respectively, p CONCLUSION: Although TNBC is associated with poor clinical outcome, differences in all-cause mortality in women with TNBC remain significantly influenced by MetS. TNBC patients with 3-4 MetS components have 10-year all-cause survival rates over 35% lower than TNBC survivors with no MetS components. This finding highlights the importance of women’s overall health status and medical condition, even after the diagnosis of an aggressive breast cancer. Table 1. Breast cancer and all-cause survival rates by MetS group.MetSNBreast Cancer Survival (%)All-Cause Survival (%)3-year5-year10-yearp-value3-year5-year10-yearp-value01789087840.098782710.0081-23238983798777653-443877363836445 Citation Format: Yuan Yuan, Rebecca Nelson, Kathy Pan, Jessica Yan, Susan E Yost, Rami Nassir, Rowan Chlebowski. Metabolic syndrome impacts survival in postmenopausal women with triple negative breast cancer: Results from the women’s health initiative [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-03.
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- 2020
21. Weight loss, diet composition and breast cancer incidence and outcome in postmenopausal women
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Rowan T. Chlebowski, Kathy Pan, Juhua Luo, and Aaron K. Aragaki
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0301 basic medicine ,obesity ,medicine.medical_specialty ,law.invention ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,Weight loss ,law ,medicine ,Women's Health Initiative ,skin and connective tissue diseases ,Obstetrics ,business.industry ,Incidence (epidemiology) ,Weight change ,waist circumference ,medicine.disease ,Body Weight Maintenance ,Obesity ,3. Good health ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Research Perspective ,weight loss ,medicine.symptom ,business - Abstract
Two complementary studies in separate components of the Women’s Health Initiative (WHI) examined relationships among weight loss, diet composition and breast cancer incidence and outcome in postmenopausal women. In the WHI Observational Study, 61,335 postmenopaus al women had their weight change determined over a 3-year period with subsequent follow-up. Women with weight loss greater than or equal to 5% had significantly lower breast cancer incidence compared to women with stable weight. In the WHI Dietary Modification randomized clinical trial involving 48,835 postmenopausal women, implementation of a low-fat eating pattern significantly reduced deaths after breast cancer. Thus, moderation regarding dietary composition and body weight maintenance can reduce a postmenopausal woman’s risk of being diagnosed with breast cancer and of dying after breast cancer.
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- 2019
22. Abstract P1-08-10: Insulin resistance and breast cancer incidence and mortality in postmenopausal women
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T E Rohan, Gloria Y.F. Ho, EM Cespedes Feliciano, Mara Z. Vitolins, Marc J. Gunter, Kathy Pan, Lucile L. Adams-Campbell, Rebecca A. Nelson, Rowan T. Chlebowski, Joanne E. Mortimer, Arti Hurria, and T-Yd Cheng
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Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Hazard ratio ,Cancer ,medicine.disease ,National Death Index ,Insulin resistance ,Breast cancer ,Internal medicine ,medicine ,Population study ,education ,business ,Cause of death - Abstract
Background:Obese postmenopausal women are at higher breast cancer risk potentially driven by hyperinsulinemia. However, reports of insulin level associations with breast cancer incidence and survival are inconsistent. Therefore, we examined associations among insulin resistance by homeostasis model assessment-insulin resistance (HOMA-IR) index and incident breast cancer, deaths from breast cancer, and deaths after breast cancer in postmenopausal women participating in the Women's Health Initiative (WHI). Patients and Methods:From the 161,808 postmenopausal women, aged 50-79 years, enrolled at 40 US clinical centers from 1993 through1998 in WHI clinical trials or the observational study, 22,837 with available fasting serum insulin and glucose by the same methodology and no prior breast cancer represent the current study population. The exposure was insulin resistance (HOMA-IR index) as [fasting insulin (qIU/ml) times fasting glucose (mg/dL) / 22.5. Survival by cause was determined by central medical record or death certificate review, enhanced by National Death Index queries. Breast cancers, initially ascertained by serial survey, were confirmed by medical record review. Associations between HOMA-IR quartiles and breast cancer outcomes were examined using Cox multi- variate proportional hazards models with results reported as hazard ratios (HR) and 95% confidence intervals. Results: At entry, women in the highest HOMA-IR quartile were more likely to be Black, have lower education level, have higher body mass index (BMI), higher waist circumference ≥ 88 cm and lower physical activity levels, but have lower calculated five-year breast cancer risk. After 18.1 years median follow-up from randomization with 1,148 incident breast cancers, breast cancer incidence was higher in women in the highest, compared to the lowest, HOMA-IR index quartile (HR 1.39 95% CI 1.14 -1.69, P = 0.0012). Of the women with incident breast cancer, 353 (31%) have died, with cause of death available on 334 (95% of cases) where breast cancer was the most common cause of death (33%); followed by cardiovascular disease (24%); and other cancers (13%). With median post-breast cancer diagnosis follow-up of 10.5 years, breast cancer mortality was examined from breast cancer diagnosis. No association was found between death from breast cancer and HOMA-IR. However, women with breast cancer in the highest HOMA-IR quartile, compared to women in the lowest, were significantly more likely to experience death after breast cancer from any cause (HR 1.45 95% CI 1.00 - 2.09, P = 0.0488) and were at somewhat higher risk of death from cardiovascular disease (HR 1.51 95% CI 0.67 - 3.41) and other causes (HR 1.93 95% CI 0.87-4.27). Conclusion:In postmenopausal women, higher insulin resistance is associated with higher breast cancer incidence and more deaths after breast cancer, likely due to insulin influence on several causes of death. However, deaths from breast cancer, even in this older postmenopausal population, remains a major factor limiting survival which needs to be addressed. The findings suggest insulin resistance represented a potential intervention target for postmenopausal women with early stage breast cancer. Citation Format: Chlebowski RT, Pan K, Mortimer J, Cespedes Feliciano EM, Gunter MJ, Hurria A, Rohan T, Vitolins MZ, Adams-Campbell L, Ho G, Cheng T-YD, Nelson R. Insulin resistance and breast cancer incidence and mortality in postmenopausal women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-10.
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- 2019
23. Constitutional BRCA1 methylation and risk of incident triple-negative breast cancer and high-grade serous ovarian cancer
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Per E. Lønning, Oleksii Nikolaienko, Kathy Pan, Allison W. Kurian, Hans P. Eikesdal, Mary Pettinger, Garnet L. Anderson, Ross L. Prentice, Rowan T. Chlebowski, and Stian Knappskog
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Ovarian Neoplasms ,Cancer Research ,Oncology ,BRCA1 Protein ,Case-Control Studies ,Humans ,Female ,Triple Negative Breast Neoplasms ,DNA Methylation ,Promoter Regions, Genetic - Abstract
ImportanceAbout 25% of all triple-negative breast cancers (TNBCs) and 10% to 20% of high-grade serous ovarian cancers (HGSOCs) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC or HGSOC is unknown.ObjectiveTo assess the potential association between white blood cell BRCA1 promoter methylation and subsequent risk of incident TNBC and HGSOC.Design, Setting, and ParticipantsThis case-control study included women who were participating in the Women’s Health Initiative study who had not received a diagnosis of either breast or ovarian cancer before study entrance. A total of 637 women developing incident TNBC and 511 women developing incident HGSOC were matched with cancer-free controls (1841 and 2982, respectively) in a nested case-control design. Cancers were confirmed after central medical record review. Blood samples, which were collected at entry, were analyzed for BRCA1 promoter methylation by massive parallel sequencing. The study was performed in the Mohn Cancer Research Laboratory (Bergen, Norway) between 2019 and 2022.Main Outcomes and MeasuresAssociations between BRCA1 methylation and incident TNBC and incident HGSOC were analyzed by Cox proportional hazards regression.ResultsOf 2478 cases and controls in the TNBC group and 3493 cases and controls in the HGSOC group, respectively, 7 (0.3%) and 3 (0.1%) were American Indian or Alaska Native, 46 (1.9%) and 30 (0.9%) were Asian, 1 (0.04%) and 1 (0.03%) was Native Hawaiian or Pacific Islander, 326 (13.2%) and 125 (3.6%) were Black or African, 56 (2.3%) and 116 (3.3%) were Hispanic, 2046 (82.6%) and 3257 (93.2%) were White, and 35 (1.4%) and 35 (1.0%) were multiracial. Median (range) age at entry was 62 (50-79) years, with a median interval to diagnosis of 9 (TNBC) and 10 (HGSOC) years. Methylated BRCA1 alleles were present in 194 controls (5.5%). Methylation was associated with risk of incident TNBC (12.4% methylated; HR, 2.35; 95% CI, 1.70-3.23; P P P P = .003). Across individuals, methylation was not haplotype-specific, arguing against an underlying cis-acting factor. Within individuals, BRCA1 methylation was observed on the same allele, indicating clonal expansion from a single methylation event. There was no association found between BRCA1 methylation and germline pathogenic variant status.Conclusions and RelevanceThe results of this case-control suggest that constitutional normal tissue BRCA1 promoter methylation is significantly associated with risk of incident TNBC and HGSOC, with potential implications for prediction of these cancers. These findings warrant further research to determine if constitutional methylation of tumor suppressor genes are pancancer risk factors.
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- 2022
24. Low-Fat Dietary Modification and Risk of Ductal Carcinoma
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Rita, Peila, Rowan, Chlebowski, JoAnn E, Manson, Tracy E, Crane, Dorothy S, Lane, Nazmus, Saquib, Aladdin H, Shadyab, Fred K, Tabung, Ana, Barac, Zhenzhen, Zhang, Kathy, Pan, Sylvia, Wassertheil-Smoller, and Thomas E, Rohan
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Postmenopause ,Carcinoma, Intraductal, Noninfiltrating ,Risk Factors ,Humans ,Breast Neoplasms ,Female ,Middle Aged ,Diet, Fat-Restricted ,Negative Results ,Aged ,Follow-Up Studies ,Proportional Hazards Models - Abstract
Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinomaA total of 48,835 postmenopausal women, ages 50-79 years at enrollment, with no breast cancer history and ≥32% of total energy intake from fat, were randomly assigned either to a dietary intervention (During 18.7 years (median) cumulative follow-up, including intervention (∼8.7 years) and post-intervention phases (∼13.0 years), 817 DCIS cases were ascertained. No evidence of an association between the DM intervention and DCIS risk was observed overall, or by trial phase (intervention and post-intervention). Similarly, no associations were found in subgroups defined by potential risk factors for DCIS.DM aiming to reduce fat intake was not associated with altered risk of DCIS.These results do not provide evidence of an association between dietary fat reduction and the risk of DCIS among postmenopausal women.
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- 2021
25. Metabolic syndrome risk components and mortality after triple-negative breast cancer diagnosis in postmenopausal women in the Women's Health Initiative
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Candyce H. Kroenke, Kathy Pan, Joanne E. Mortimer, Yangbo Sun, Yuan Yuan, Mara Z. Vitolins, Lucile L. Adams-Campbell, Rami Nassir, Jessica Yan, Juhua Luo, Susan E. Yost, Robert A. Wild, JoAnn E. Manson, Rebecca A. Nelson, Nazmus Saquib, Rowan T. Chlebowski, and Aladdin H. Shadyab
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Cancer Research ,medicine.medical_specialty ,Triple Negative Breast Neoplasms ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Triple-negative breast cancer ,Metabolic Syndrome ,business.industry ,Proportional hazards model ,Women's Health Initiative ,Hazard ratio ,medicine.disease ,Confidence interval ,Postmenopause ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,Metabolic syndrome ,business - Abstract
Background Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative. Methods Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status. Results Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components. Conclusions Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.
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- 2020
26. Protein Intake by Source and Breast Cancer Incidence and Mortality: The Women’s Health Initiative
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Joanne E. Mortimer, Ross L. Prentice, Joseph C. Larson, Marian L. Neuhouser, Dorothy S. Lane, Kathy Pan, JoAnn E. Manson, Thomas E. Rohan, Rowan T. Chlebowski, and Linda Van Horn
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Women's Health Initiative ,Incidence (epidemiology) ,Medical record ,Hazard ratio ,Lower risk ,medicine.disease ,National Death Index ,Confidence interval ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030212 general & internal medicine ,business ,skin and connective tissue diseases ,AcademicSubjects/MED00010 - Abstract
BackgroundPrior studies of dietary protein intake and breast cancer have been mixed and were limited by dietary self-report measurement error.MethodsBiomarker-calibrated total protein intake and estimated vegetable protein and animal protein intake were determined from baseline food frequency questionnaires in 100 024 Women’s Health Initiative participants. Associations between total, animal, and vegetable protein intake and breast cancer incidence, deaths from breast cancer, and deaths after breast cancer were estimated using Cox proportional hazards regression. Breast cancers were verified by medical record review and survival outcomes enhanced by National Death Index queries. All statistical tests were 2-sided.ResultsAfter 14 years of follow-up, there were 6340 incident breast cancers, 764 deaths from breast cancer, and 2059 deaths after breast cancer. In multivariable analyses, higher calibrated total protein intake was not associated with breast cancer incidence or deaths from or after breast cancer. Vegetable protein intake was associated with statistically significantly lower breast cancer incidence (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.96 to 0.99, Ptrend = .006) and statistically significantly lower risk of death after breast cancer (HR = 0.93, 95% CI = 0.91 to 0.97, Ptrend < .001) but not with deaths from breast cancer. In contrast, higher animal protein intake was associated with statistically significantly higher breast cancer incidence (HR = 1.03, 95% CI = 1.01 to 1.06, Ptrend = .02) but not with deaths from or after breast cancer.ConclusionsCalibrated total protein intake was not associated with breast cancer incidence or mortality. Higher vegetable protein intake was associated with lower breast cancer incidence and lower risk of death after breast cancer. Higher animal protein intake was associated with higher breast cancer incidence.
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- 2020
27. Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial
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Juhua Luo, Aaron K. Aragaki, Joanne E. Mortimer, Thomas E. Rohan, Candyce H. Kroenke, Bette J. Caan, Linda Snetselaar, Kerryn W. Reding, JoAnn E. Manson, Rowan T. Chlebowski, Marian L. Neuhouser, Michael S. Simon, Kathy Pan, and Dorothy S. Lane
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Cancer Research ,medicine.medical_specialty ,Waist ,Breast Neoplasms ,Risk Assessment ,High cholesterol ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Aged ,Metabolic Syndrome ,business.industry ,Women's Health Initiative ,Hazard ratio ,Middle Aged ,medicine.disease ,Dietary Fats ,Confidence interval ,Postmenopause ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,Metabolic syndrome ,Waist Circumference ,business - Abstract
Background In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components. Methods In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score. Results HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01). Conclusions While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk. Registry ClinicalTrials.gov (NCT00000611).
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- 2020
28. The association between type 2 diabetes mellitus and bladder cancer risk among postmenopausal women
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Pengcheng Xun, Juhua Luo, Michael Hendryx, Kathy Pan, Lihong Qi, Ka He, Aladdin H. Shadyab, and Yueyao Li
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Diabetes treatment ,Urologic Diseases ,Cancer Research ,medicine.medical_specialty ,Aging ,Epidemiology ,Oncology and Carcinogenesis ,Article ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Medicine ,2.1 Biological and endogenous factors ,Humans ,030212 general & internal medicine ,Prospective Studies ,Family history ,Aetiology ,Metabolic and endocrine ,Nutrition ,Cancer ,Aged ,Bladder cancer ,business.industry ,Prevention ,Confounding ,Diabetes ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,Diabetes duration ,Postmenopause ,Oncology ,Diabetes Mellitus, Type 2 ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Female ,business ,Body mass index ,Type 2 - Abstract
INTRODUCTION:Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS:A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS:During a median follow-up of 18.5years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. CONCLUSION:Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.
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- 2020
29. Dietary Modification and Breast Cancer Mortality: Long-Term Follow-Up of the Women’s Health Initiative Randomized Trial
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Jean Wactawski-Wende, Dorothy S. Lane, Linda Snetselaar, Rowan T. Chlebowski, Thomas E. Rohan, Ana Barac, JoAnn E. Manson, Ross L. Prentice, Juhua Luo, Garnet L. Anderson, Aaron K. Aragaki, Yasmin Mossavar-Rahmani, Marian L. Neuhouser, Karen C. Johnson, Kathy Pan, and Cynthia A. Thomson
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Breast cancer mortality ,MEDLINE ,Breast Neoplasms ,Kaplan-Meier Estimate ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Survival rate ,Diet, Fat-Restricted ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Incidence (epidemiology) ,Women's Health Initiative ,Incidence ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,Dietary Fats ,Postmenopause ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,business ,Follow-Up Studies - Abstract
PURPOSE Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence. METHODS In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings. RESULTS During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02). CONCLUSION Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.
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- 2020
30. The underreporting of phase III chemo-therapeutic clinical trial data of older patients with cancer: A systematic review
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Edith Starbuck, Thuy T. Koll, Beverly Canin, Jessica L. Krok-Schoen, Kathy Pan, Armin Shahrokni, Karlynn BrintzenhofeSzoc, Jennifer L. Lund, Christine D. Hsu, Amy R. MacKenzie, Ritika Vankina, Brian Jang, and Ira R. Parker
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Male ,medicine.medical_specialty ,Phases of clinical research ,Article ,03 medical and health sciences ,0302 clinical medicine ,Older patients ,Neoplasms ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Aged ,Clinical Oncology ,Descriptive statistics ,business.industry ,Cancer ,medicine.disease ,United States ,Clinical trial ,Treatment Outcome ,Oncology ,Geriatric oncology ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,Family medicine ,Female ,Geriatrics and Gerontology ,business - Abstract
Purpose Inspired by the American Society of Clinical Oncology's recommendations to strengthen the evidence base for older adults with cancer, the purpose of this systematic review is to identify the reporting of treatment efficacy and adverse events specific to older adults with cancer in Phase III chemo-therapeutic clinical trials. This review also investigates the frequency with which these data points were reported in the literature to identify gaps in reporting and opportunities to expand the knowledge base on clinical outcomes for older adults with cancer. Methods Chemo-therapeutic clinical trial data published from July 1, 2016 to June 30, 2017 was reviewed. Manuscripts (n = 929) were identified based on keyword searches of EMBASE and PubMed. After removal of duplicates (n = 116) and articles that did not meet this study's inclusion criteria (n = 654), 159 articles were identified for review. Results Reviewed papers were published in 36 different scientific journals and included twenty-five different cancer types. Of the 159 articles, 117 (73.6%) reported age-specific medians and 75 (47.2%) included stratifications of data by age. Treatment efficacy was reported in 96.2% of the articles with 39.9% reporting effectiveness of treatment by age. Reporting of adverse events was included in 84.9% of the articles with only 8.9% reporting these events stratified by age. Conclusion Results suggest inadequate reporting of treatment efficacy and adverse events as well as basic descriptive statistics about the age distribution of study subjects. Conscious efforts are needed to address these deficiencies at every level of planning and conducting clinical trials as wells as reporting outcomes stratified by age. Ultimately, standardized reporting could lead to improved treatment decisions and outcomes for older adults with cancer.
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- 2020
31. Change in longitudinal trends in sleep quality and duration following breast cancer diagnosis: results from the Women’s Health Initiative
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Lauren Hale, Michelle J. Naughton, Tracy E. Crane, Electra D. Paskett, Michael L. Pennell, Gregory S. Young, Kathy Pan, Randi E. Foraker, Chloe Beverly, Elizabeth M. Cespedes Feliciano, and Suzanne C. Danhauer
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medicine.medical_specialty ,Pediatrics ,business.industry ,Women's Health Initiative ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Sleep in non-human animals ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Oncology ,030220 oncology & carcinogenesis ,Epidemiology ,Epidemiology of cancer ,Insomnia ,medicine ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Depression (differential diagnoses) - Abstract
Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women’s Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis. To examine sleep duration, we fit a logistic regression model with random effects for both short (, Epidemiology: Long-term sleep patterns unaffected by breast cancer diagnosis Despite frequent reports of poor sleep among survivors of breast cancer, a large epidemiological study has found no evidence that diagnosis of invasive breast cancer long-term sleep problems. Chloe Beverly of The Ohio State University in Columbus, USA, and colleagues examined long-term patterns in sleep quality, sleep duration and symptoms of depression among more than 12,000 participants of the Women’s Health Initiative who were diagnosed with breast cancer. On the whole, they found that women developed insomnia at a slightly slower rate after their diagnosis and the prevalence of depression went down, with little change in sleep duration. Although some women may experience cancer-related sleep disturbances shortly after their diagnosis and treatment, the findings suggest that, over the long term, most sleep issues remain consistent compared to before diagnosis.
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- 2018
32. Abstract P6-12-02: Racial/ethnic differences in sleep quality and duration among breast cancer survivors: Results from the women's health initiative (WHI)
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Elizabeth M. Cespedes Feliciano, Kathy Pan, CM Beverly, S Danhauer, Electra D. Paskett, Gregory S. Young, R Foraker, Tracy E. Crane, Michael L. Pennell, Michelle J. Naughton, and L Hale
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Gerontology ,Cancer Research ,Breast cancer ,Oncology ,Sleep quality ,business.industry ,Women's Health Initiative ,medicine ,Racial/ethnic difference ,Duration (project management) ,medicine.disease ,business - Abstract
BACKGROUND: Sleep is a crucial factor for optimal health, but breast cancer survivors often report poor sleep quality. It is estimated 20-70% of survivors have at least one sleep problem, which contribute to quality of life and health differences among survivors. Minority groups tend to have poorer sleep quality and shorter sleep duration than Non-Hispanic Whites (NHW). African-Americans (AA) with breast cancer have a poorer prognosis than NHW for each stage-specific diagnosis and are twice as likely as NHW to report short sleep duration, yet survivor studies are still lacking in AA participants. The purpose of this study was to examine sleep quality and duration patterns before and after cancer diagnosis by race/ethnicity among WHI breast cancer survivors. METHODS: There were 12,098 postmenopausal women diagnosed with invasive breast cancer after WHI enrollment who were eligible for this secondary analysis. Baseline demographic and clinical characteristics were described. The WHI Insomnia Rating Scale (WHIIRS) was measured at multiple time points pre- and post-diagnosis. A higher WHIIRS scores (0-20 points) indicates greater sleep disturbance and ≥9 points identifies clinical insomnia. A linear mixed model was fit to the WHIIRS sleep quality data to examine if the trend in sleep quality with time changed following a cancer diagnosis. For short ( RESULTS: The majority of participants were NHW (87.4%), mean age at diagnosis was 70.3 years, and 75% had localized breast cancer at diagnosis. At baseline, 30% of women had insomnia. The lowest average WHIIRS score was 5.6 among Asians, and the highest was 6.6 among American-Indians and NHWs (p=0.02). AAs had the most women sleeping ≤5 hrs/night and NHW had the least (19.6% vs 5.7%, p DISCUSSION: Sleep is an appealing area to target for improvement due to the multiple ways it can be treated. With increasing survival rates, there is an emphasis on improving quality of life in survivors. Our results span 20 years pre-diagnosis to 15 years post-diagnosis and are similar to shorter follow-up studies which found most women's sleep problems resolve within a few years of treatment completion. The lack of difference by race was an unexpected finding in another similar longitudinal study, which suggested most differences are seen in cross-sectional sleep studies. This study adds to the literature on longitudinal sleep data, especially to the little data on sleep trajectories in minority breast cancer survivors. Citation Format: Beverly CM, Naughton M, Foraker R, Pennell M, Young G, Hale L, Crane T, Pan K, Danhauer S, Feliciano E, Paskett E. Racial/ethnic differences in sleep quality and duration among breast cancer survivors: Results from the women's health initiative (WHI) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-02.
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- 2018
33. Value-based genomics
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Sumanta K. Pal, Jun Gong, Ravi Salgia, Kathy Pan, and Marwan Fakih
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0301 basic medicine ,medicine.medical_specialty ,Genomic profiling ,business.industry ,Cost effectiveness ,pathways ,Value based care ,Genomics ,Review ,DNA sequencing ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,value-based care ,Precision oncology ,030220 oncology & carcinogenesis ,precision oncology ,Medicine ,Medical physics ,next-generation sequencing ,business ,cost-effectiveness - Abstract
// Jun Gong 1 , Kathy Pan 2 , Marwan Fakih 1 , Sumanta Pal 1 and Ravi Salgia 3 1 Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA 2 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA 3 Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA Correspondence to: Ravi Salgia, email: rsalgia@coh.org Keywords: next-generation sequencing; precision oncology; pathways; cost-effectiveness; value-based care Received: November 30, 2017 Accepted: January 19, 2018 Epub: January 30, 2018 Published: March 20, 2018 ABSTRACT Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge. In this review, we highlight available data through a pre-established and conceptualized framework for evaluating value-based medicine to assess the cost (efficiency), clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in cancer care. We also provide perspectives on future directions of next-generation sequencing from targeted panels to whole-exome or whole-genome sequencing and describe potential strategies needed to attain value-based genomics.
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- 2018
34. Desert dust episodes during pregnancy are associated with increased preterm delivery in French Guiana
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Mathieu Nacher, Malika Leneuve, Celia Basurko, Alphonse Louis, Dominique Dotou, Stephanie Bernard, Kathy Pannechou, Karim Merad Boudia, Lindsay Osei, Fabrice Quet, and Najeh Hcini
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preterm birth ,air pollution ,airborne particulate matter ,seasons ,French Guiana ,Public aspects of medicine ,RA1-1270 - Abstract
Preterm deliveries are a major multifactorial public health problem in French Guiana. Desert dust episodes have been associated with preterm delivery in Guadeloupe, a territory with similarities to French Guiana. We thus tried to replicate this finding in the context of French Guiana. A retrospective ecological cohort study combined daily PM10 concentration measurements during pregnancy and term at delivery extracted from French Guiana’s computerized pregnancy delivery registry. Daily PM10 concentrations during the course of pregnancy were analyzed as mean concentrations and as the proportion of intense dust episodes (≥55 μg PM10/m3). These exposure variables were studied in relation to the outcome of preterm delivery. Overall, 3,321 pregnant women with complete daily PM10 measurements were included, of whom 374 (11.26%) delivered prematurely. Among preterm deliveries, 168 (44.9%) were spontaneous deliveries and 206 (55.1%) were induced. Rank-sum tests showed that, for spontaneous and induced spontaneous deliveries, both mean PM10 concentrations and proportions of intense desert dust episodes were significantly greater among preterm births than among term births. Although the proportion of intense desert dust episodes during pregnancy was significantly associated with spontaneous preterm deliveries, the relation was U-shaped, with an adjusted odds ratio (AOR) = 2 (95%CI = 1.2–3.1) for lowest values relative to median values and AOR = 5.4 (95%CI = 3.2–8.9) for the highest values relative to median values. Similarly, the proportion of intense desert dust episodes during pregnancy was also significantly associated with induced preterm deliveries in a U-shaped manner (AOR = 2.7 (95%CI = 1.6–4.5) for the lowest relative to median values and AOR = 6.8 (95%CI = 3.9–11.9) for the highest relative to median values). Although in our study the relation between PM10 concentrations appeared non-linear, the highest mean concentrations and intense desert dust episodes were indeed associated with both spontaneous and induced preterm delivery.
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- 2024
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35. Abstract 789: Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative
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Maeve Mullooly, Kathleen Bennett, Juhua Luo, Sowmya Vasan, Gretchen L. Gierach, Thomas E. Rohan, Rowan T. Chlebowski, Lihong Qi, Aladdin H. Shadyab, Kathy Pan, and Dorothy S. Lane
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Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Women's Health Initiative ,Hazard ratio ,Cancer ,medicine.disease ,Clinical trial ,Breast cancer ,Oncology ,medicine ,Mammography ,Breast disease ,Family history ,skin and connective tissue diseases ,business - Abstract
INTRODUCTION: Benign breast disease (BBD) describes a heterogeneous group of premalignant lesions associated with an increased risk of breast cancer development, especially in those with proliferative BBD with atypia. Whether BBD is associated with higher all-cause mortality is unsettled. Therefore, we examined the association between incident BBD, BBD histotypes and all-cause and breast cancer-specific mortality among WHI participants. METHODS: Included were 68,132 postmenopausal women enrolled in the WHI clinical trials from 1993-1998 at 40 US clinical centres, followed up through March 2019. In these trials, serial mammography was mandated and compliance was high. Cases were participants in the BBD ancillary study (AS)130 with incident BBD confirmed by central pathology review. The comparison group included all other clinical trial participants (intervention and control groups). Cox proportional hazard regression models, stratified by baseline age, clinical trial arms and WHI extension study participation, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality in association with BBD. Analyses were adjusted for age, race/ethnicity, education, income, smoking, BMI, waist circumference, energy intake, alcohol, physical activity, reproductive factors, family history of breast cancer, Gail model score, history of menopausal hormone therapy (MHT) use and history of comorbidities. RESULTS: Compared to women without incident BBD (n=43,439), women with incident BBD (n=3,467) were younger (p1.75 (p CONCLUSIONS: In postmenopausal women, while a BBD diagnosis was associated with a statistically significant higher risk of breast cancer-specific mortality, irrespective of histotype, a BBD diagnosis was not associated with higher all-cause mortality. Citation Format: Maeve Mullooly, Kathy Pan, Sowmya Vasan, Gretchen L. Gierach, Dorothy S. Lane, Aladdin H. Shadyab, Juhua Luo, Lihong Qi, Kathleen E. Bennett, Thomas E. Rohan, Rowan Chlebowski. Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 789.
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- 2021
36. Abstract P2-09-06: Addition of ovarian function suppression to endocrine therapy in premenopausal women with early breast cancer: A meta-analysis
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NF Col, Kathy Pan, and R Chlebowski
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Oncology ,Cancer Research ,medicine.medical_specialty ,Aromatase inhibitor ,medicine.drug_class ,business.industry ,Hazard ratio ,Cancer ,medicine.disease ,chemistry.chemical_compound ,Breast cancer ,Exemestane ,chemistry ,Estrogen ,Internal medicine ,medicine ,Adjuvant therapy ,business ,Tamoxifen ,medicine.drug - Abstract
Introduction The Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and EXemestane Trial (TEXT), together with the Austrian Breast Cancer Study Group (ABCSG-12)and the Eastern Cooperative Oncology Group 3193 (E-3193 trials, have examined adding ovarian function suppression (OFS) using gonadotropin–releasing hormone (GnRH) agonists to endocrine therapy in premenopausal women with early stage breast cancer. However, OFS with GnRH agonist plus aromatase inhibitor has subsequently been found to not consistently reduce estradiol levels to optimal target in the SOFT-EST study (JCO 2016; 34:1584) and implications of these study findings for clinical practice are controversial. Therefore, to further examine this issue, we conducted a systematic literature review and meta-analysis of available evidence. Methods We updated a recently published literature review of randomized clinical trials (JCO 2016; 34:1689) through June 1, 2016 using the keywords “breast cancer,” “ovarian function suppression,” “tamoxifen,” and “aromatase inhibitor”. Of 683 of records identified through database searching, the 4 studies named above met inclusion criteria and were included in the quantitative synthesis. Information on disease-free survival (DFS) and overall survival was examined using hazard ratio (HR) and 95% confidence interval (CI). Because of significant heterogeneity in one performed meta-analyses, the random-effects (DerSimonian and Laird) method was used to estimate the combined RR for studies (Open MetaAnalyst). Results Combining ABCSG-12, SOFT and TEXT trial findings, OFS addition to aromatase inhibitor resulted in 65 fewer DFS events across the 3 trials compared to OFS addition to tamoxifen (350 DFS events vs. 415 DFS events, respectively, HR 0.89, 95% CI 0.57-1.39, P=0.62, Tau2 =0.09, heterogeneity P Conclusion In conclusion, the apparent discordance between DFS and overall survival in the aromatase inhibitor and OFS trials and the results suggesting incomplete and/or intermittent estrogen suppression with GNRH analogs in the SOFT-EST trial suggest that adoption of OFS plus aromatase inhibitor use as adjuvant therapy in premenopausal women with early stage breast cancer may be premature. Longer term survival analyses of the endocrine therapy trials are needed before reliable risks and benefits of aromatase inhibitor plus OFS and tamoxifen plus OFS use as adjuvant therapy can be determined. Citation Format: Chlebowski R, Pan K, Col NF. Addition of ovarian function suppression to endocrine therapy in premenopausal women with early breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-06.
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- 2017
37. Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women’s Health Initiative
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Lawrence S. Phillips, Aaron K. Aragaki, Aladdin H. Shadyab, Gloria Y.F. Ho, Jean Wactawski-Wende, JoAnn E. Manson, Joanne E. Mortimer, Jinnie J. Rhee, Arti Hurria, Kathy Pan, Nazmus Saquib, Rami Nassir, Rowan T. Chlebowski, Rebecca A. Nelson, Thomas E. Rohan, and Delphine J. Lee
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Cancer Research ,medicine.medical_specialty ,030209 endocrinology & metabolism ,National Death Index ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Risk Factors ,Internal medicine ,Cause of Death ,Neoplasms ,Medicine ,Humans ,Public Health Surveillance ,Cause of death ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Cancer Death Rate ,Proportional hazards model ,business.industry ,Women's Health Initiative ,Hazard ratio ,Articles ,Middle Aged ,medicine.disease ,United States ,Postmenopause ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,Insulin Resistance ,business ,Body mass index ,Follow-Up Studies - Abstract
Background Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women’s Health Initiative (WHI). Methods Eligible were a subsample of 22 837 WHI participants aged 50–79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. Results During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). Conclusions High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.
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- 2019
38. Capecitabine-induced hypertriglyceridemia: a rare but clinically relevant treatment-related adverse event
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May Cho, Phyllis Kim, An Uche, Kathy Pan, Ritika Vankina, James J. Yeh, and Jun Gong
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medicine.medical_specialty ,Chemotherapy ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,Hypertriglyceridemia ,Gastroenterology ,Case Report ,Disease ,medicine.disease ,Discontinuation ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Acute pancreatitis ,030212 general & internal medicine ,Intensive care medicine ,business ,Adverse effect ,medicine.drug - Abstract
Capecitabine-induced hypertriglyceridemia (CIHT) represents an increasingly significant treatment-related adverse event from capecitabine given its potential for both acute complications (acute pancreatitis) and chronic metabolic complications (cardiovascular disease). The incidence of CIHT is relatively rare and the majority of cases thus far reported have been managed with lipid-lowering therapy and/or discontinuation of capecitabine followed by resumption of the drug upon normalization of triglyceride levels. We present among the first U.S. cases of CIHT to be reported in the published literature and highlight management approaches for this rare but clinically relevant adverse event. Further understanding of the mechanisms of CIHT and its long-term adverse effects as well as effective preventive strategies, interventions, and monitoring strategies are prudent given the widespread and often prolonged use of capecitabine-based chemotherapy in gastrointestinal and other cancers.
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- 2018
39. Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials
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Lewis H. Kuller, Kathy Pan, Electra D. Paskett, Margery Gass, JoAnn E. Manson, Karen C. Johnson, Jane A. Cauley, Rowan T. Chlebowski, Garnet L. Anderson, Michael S. Simon, Ross L. Prentice, Thomas E. Rohan, Maryam Sattari, Dorothy S. Lane, Wendy E. Barrington, Aaron K. Aragaki, and Marcia L. Stefanick
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Risk ,medicine.medical_specialty ,Hormone Replacement Therapy ,medicine.medical_treatment ,Breast Neoplasms ,Medroxyprogesterone Acetate ,Hysterectomy ,01 natural sciences ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Medroxyprogesterone acetate ,030212 general & internal medicine ,0101 mathematics ,Original Investigation ,Randomized Controlled Trials as Topic ,Aged ,Estrogens, Conjugated (USP) ,business.industry ,Incidence ,Women's Health Initiative ,Incidence (epidemiology) ,Mortality rate ,Estrogen Replacement Therapy ,010102 general mathematics ,General Medicine ,Middle Aged ,medicine.disease ,Postmenopause ,Clinical trial ,Women's Health ,Female ,Menopause ,business ,Follow-Up Studies ,medicine.drug - Abstract
IMPORTANCE: The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. OBJECTIVE: To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women’s Health Initiative clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27 347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. INTERVENTIONS: In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years’ median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years’ median intervention duration. MAIN OUTCOMES AND MEASURES: The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. RESULTS: Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P = .005) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97; P = .04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45; P
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- 2020
40. Abstract C068: Census tract-level income inequality and colorectal cancer survival
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Manali I. Patel, Polly A. Newcomb, Shawnita Sealy-Jefferson, Jamaica R. Robinson, Dorothy S. Lane, Candace H. Kroenke, Theresa A. Hastert, Kathy Pan, Giselle Corbie-Smith, Shirley A.A. Beresford, and Kelsey A. Chun
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Poverty ,Epidemiology ,business.industry ,Hazard ratio ,Distribution (economics) ,Health equity ,American Community Survey ,Oncology ,Economic inequality ,Life expectancy ,Household income ,Medicine ,business ,Demography - Abstract
Background: Income inequality has been associated with greater mortality and lower life expectancy in many ecologic studies, particularly at the national level. At the neighborhood level, the influence of income inequality on individual health is less clear. Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Recent studies suggest that neighborhood social and built environments are associated with outcomes across the CRC continuum, including screening, risk, and survival. Few studies of neighborhood factors have examined income inequality in relation to CRC survival. Methods: We examined the association of census tract-level income inequality with survival among women who participated in the Women's Health Initiative (WHI) and were diagnosed with incident invasive CRC between 1994-2014 (N=2,595). Based on geocoded residence at diagnosis and year of diagnosis, we linked each participant to census tract-level data from the US Census and American Community Survey (ACS). Within each tract, income inequality was assessed using the ratio of the 95th and 20th percentiles for household income. Quartiles for 95/20 ratio were constructed from the distribution of 95/20 ratios across all U.S. census tracts with more than 50 households. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall and disease-specific survival. Models were adjusted for age at diagnosis, year of diagnosis, individual household income, and tract-level percent of households in poverty; subsequent models also adjusted for tumor stage at diagnosis. To explore whether the relationship between income inequality and survival differed by individual or tract-level sociodemographic characteristics, we conducted analyses stratified by race/ethnicity, individual household income, and tract-level poverty. Results: Compared to women residing in low-income-inequality census tracts, women living in tracts with the highest income inequality had modestly poorer overall survival (HR=1.24, 95% CI: 1.01-1.51, comparing highest and lowest quartiles). However, this association was not significant after adjustment for stage at diagnosis. No associations were detected for disease-specific survival. The associations between income inequality and overall or disease-specific survival were not modified by tract-level poverty, individual household income, or race/ethnicity. Conclusion: There was no association between census tract-level income inequality and CRC survival in our study. Our results suggest that the association may be confounded or even mediated by disparities in stage at diagnosis. Citation Format: Kelsey A. Chun, Jamaica R. Robinson, Candace H. Kroenke, Dorothy S. Lane, Giselle Corbie-Smith, Theresa Hastert, Shawnita Sealy-Jefferson, Manali I. Patel, Kathy Pan, Shirley A.A. Beresford, Polly A. Newcomb. Census tract-level income inequality and colorectal cancer survival [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C068.
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- 2020
41. Abstract GS5-00: Long-term influence of estrogen plus progestin and estrogen alone use on breast cancer incidence: The Women's Health Initiative randomized trials
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Lewis H. Kuller, Wendy E. Barrington, Margery Gass, Karen C. Johnson, JoAnn E. Manson, Maryam Sattari, Aaron K. Aragaki, Michael S. Simon, Garnet L. Anderson, Dorothy S. Lane, Electra D. Paskett, Marcia L. Stefanick, Jane A. Cauley, Thomas E. Rohan, Kathy Pan, Rowan T. Chlebowski, and Ross L. Prentice
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Hysterectomy ,business.industry ,Obstetrics ,Incidence (epidemiology) ,Women's Health Initiative ,medicine.medical_treatment ,Hazard ratio ,Cancer ,medicine.disease ,Menopause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Medroxyprogesterone acetate ,business ,medicine.drug - Abstract
Background: Breast cancer outcomes from the Women’s Health Initiative (WHI) Estrogen plus Progestin and Estrogen-alone trials have been reported but issues remain regarding long- term, post-intervention influence on breast cancer incidence and the influence of time from menopause to hormone therapy initiation (gap time) on breast cancer findings. Design and methods: Postmenopausal women aged 50 to 79 years with no prior breast cancer and with mammogram clearance enrolled in one of two randomized clinical trials at 40 US centers from 1993 to1998, with follow up through September, 2016. The randomized, placebo-controlled trial interventions were: conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) vs placebo (n = 8,102) for 5.6 years (median) for women with a uterus or CEE-alone (n = 5,310) vs placebo (n = 5,429) for 7.2 years (median) for women with prior hysterectomy. Annual mammography was mandated through the originally specified completion date in both trials (March 31, 2005). Incident breast cancers were verified by medical record review. Hazard ratios (HRs) were estimated using multi-variable Cox proportional hazards models. The primary outcome for these analyses was time-specific invasive breast cancer incidence rates. In each trial, participants were instructed to stop all study pills coincident with the publication of each trial’s results, in 2002 and 2004, respectively. Results: During the intervention period, with 238 incident breast cancers, CEE-alone significantly reduced breast cancer incidence (hazard ratio [HR] 0.76 95% confidence interval [CI] 0.58, 0.98, P = 0.04). As previously reported, subgroup analyses indicated CEE-alone was particularly beneficial for women with no prior HT use (interaction P = 0.04) and women with gap time >= 5 years (interaction P = 0.01). Post-intervention, through 16.1 years of cumulative follow-up, with 520 incident breast cancers, CEE-alone use continued to significantly reduce breast cancer incidence (HR 0.77 95% CI 0.65-0.92, P = 0.005) while subgroup differences were attenuated and were no longer statistically significant. During the intervention period, with 360 incident breast cancers, CEE plus MPA use significantly increased breast cancer incidence (HR 1.26 95% CI 1.02, 1.56, P = 0.04) with increase in breast cancer incidence greater in women with prior HT use (interaction P = 0.02) and women with gap time < 5 years (interaction P = 0.002). Post-intervention, through 18.3 years cumulative follow-up, with 1,003 incident breast cancers, CEE plus MPA continued to significantly increase breast cancer incidence (HR 1.29 95% CI 1.14, 1.47, P < 0.001) while subgroup differences were attenuated and were no longer statistically significant. Conclusions: CEE-alone and CEE plus MPA use have opposite effects on breast cancer incidence. CEE alone significantly decreases breast cancer incidence which is long term and persists over a decade after discontinuing use. CEE plus MPA use significantly increases breast cancer incidence which is long term and persists over a decade after discontinuing use. As a result of the attenuation of subgroup interactions: all postmenopausal women with prior hysterectomy using CEE-alone have the potential benefit of experiencing a reduction in breast cancer incidence while all postmenopausal women using CEE plus MPA have the potential risk of experiencing an increase in breast cancer incidence. Citation Format: Rowan T Chlebowski, Garnet L Anderson, Aaron K Aragaki, JoAnn E Manson, Marcia Stefanick, Kathy Pan, Wendy Barrington, Lewis H Kuller, Michael S. Simon, Dorothy Lane, Karen C Johnson, Thomas E. Rohan, Margery L.S. Gass, Jane A Cauley, Electra D. Paskett, Maryam Sattari, Ross L Prentice. Long-term influence of estrogen plus progestin and estrogen alone use on breast cancer incidence: The Women's Health Initiative randomized trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-00.
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- 2020
42. Low-fat dietary pattern and global cognitive function: Exploratory analyses of the Women's Health Initiative (WHI) randomized Dietary Modification trial
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Kathleen M. Hayden, Marian L. Neuhouser, Laura D. Baker, JoAnn E. Manson, Lihong Qi, Jean Wactawski-Wende, Karen C. Johnson, Kathy Pan, Linda Snetselaar, Rowan T. Chlebowski, Aaron K. Aragaki, Ross L. Prentice, Steve Rapp, Lorena Garcia, and Victor W. Henderson
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Aging ,Womens Health Initiative ,medicine.medical_specialty ,Research paper ,Clinical Trials and Supportive Activities ,Low-fat dietary pattern ,01 natural sciences ,law.invention ,03 medical and health sciences ,Cognition ,Dietary modification ,0302 clinical medicine ,Randomized controlled trial ,Clinical Research ,law ,Internal medicine ,Behavioral and Social Science ,Acquired Cognitive Impairment ,medicine ,Dementia ,030212 general & internal medicine ,Women's Health Initiative ,0101 mathematics ,Nutrition ,2. Zero hunger ,lcsh:R5-920 ,business.industry ,Prevention ,Incidence (epidemiology) ,010102 general mathematics ,Hazard ratio ,Neurosciences ,General Medicine ,medicine.disease ,Confidence interval ,Brain Disorders ,3. Good health ,Good Health and Well Being ,Neurological ,Mental health ,Observational study ,Randomized clinical trial ,lcsh:Medicine (General) ,business - Abstract
Background: Meta-analyses of observational studies associate adherence to several dietary patterns with cognitive health. However, limited evidence from full scale, randomized controlled trials precludes causal inference regarding dietary effects on cognitive function. Methods: The Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, in 48,835 postmenopausal women, included a subset of 1,606 WHI Memory Study (WHIMS) participants >= 65 years old, to assess low-fat dietary pattern influence on global cognitive function, evaluated with annual screening (Modified Mini–Mental State Examinations [3MSE]). Participants were randomized by a computerized, permuted block algorithm, stratified by age group and center, to a dietary intervention (40%) to reduce fat intake to 20% of energy and increase fruit, vegetable and grain intake or usual diet comparison groups (60%). The study outcome was possible cognition impairment (failed cognitive function screening) through the 8.5 year (median) dietary intervention. Those failing screening received a comprehensive, multi-phase cognitive function assessment to classify as: no cognitive impairment, mild cognitive impairment, or probable dementia. Exploratory analyses examined the composite endpoint of death after possible cognitive impairment through 18.7 years (median) follow-up. The WHI trials are registered at ClinicalTrials.gov:NCT00000611. Findings: Among the 1,606 WHIMS participants, the dietary intervention statistically significantly reduced the incidence of possible cognitive impairment (n = 126; hazard ratio [HR] 0.59 95% confidence interval [CI] 0.38–0. 91, P = 0.01) with HR for dietary influence on subsequent mild cognitive impairment of 0.65 (95% CI 0.35–1.19) and HR of 0.63 (95% CI 0.19–2.10) for probable dementia (PD). Through 18.7 years, deaths from all-causes after possible cognitive impairment were non-significantly lower in the dietary intervention group (0.56% vs 0.77%, HR 0.83 95% CI 0.35 to 2.00, P = 0.16). Interpretation: Adoption of a low-fat eating pattern, representing dietary moderation, significantly reduced risk of possible cognitive impairment in postmenopausal women. Funding: Several Institutes of the US National Institutes of Health. Keywords: Cognition, Dietary modification, Low-fat dietary pattern, Randomized clinical trial, Women's Health Initiative
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- 2020
43. Reply to F. Conforti et al
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Kathy Pan, Rowan T. Chlebowski, and Linda D. Bosserman
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Oncology ,Cancer Research ,medicine.medical_specialty ,Immunologic Factors ,business.industry ,Ovary ,MEDLINE ,Breast Neoplasms ,Combined Modality Therapy ,medicine.anatomical_structure ,Adjuvants, Immunologic ,Internal medicine ,Correspondence ,medicine ,Humans ,Female ,business - Published
- 2019
44. Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index
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Tongguang Cheng, Andrew J. Dannenberg, Candyce H. Kroenke, Rami Nassir, Rowan T. Chlebowski, Lindsay L. Peterson, Dorothy S. Lane, Rhonda Arthur, Sylvia Wassertheil-Smoller, JoAnn E. Manson, Juhua Luo, Thomas E. Rohan, Neil M. Iyengar, Kathy Pan, Elizabeth M. Cespedes Feliciano, and Victor Kamensky
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Cancer Research ,medicine.medical_specialty ,business.industry ,Women's Health Initiative ,Hazard ratio ,medicine.disease ,Obesity ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Oncology ,Quartile ,030220 oncology & carcinogenesis ,Internal medicine ,Body Fat Measurement ,medicine ,030212 general & internal medicine ,business ,Prospective cohort study ,Body mass index - Abstract
Importance Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)–positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. Objective To investigate the association between body fat and breast cancer risk in women with normal BMI. Design, Setting, and Participants This ad hoc secondary analysis of the Women’s Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018. Main Outcomes and Measures Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants. Results Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone–binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass. Conclusions and Relevance In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women. Trial Registration ClinicalTrials.gov identifier:NCT00000611
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- 2019
45. Medication use trajectories of postmenopausal breast cancer survivors and matched cancer-free controls
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Rowan T. Chlebowski, Michael S. Simon, Jennifer Livaudais-Toman, Roberta M. Ray, Elizabeth C. Bluhm, Meryl S. LeBoff, Electra D. Paskett, Shannon D. Sullivan, Kathy Pan, Marcia L. Stefanick, and Robert B. Wallace
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Breast Neoplasms ,Comorbidity ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Survivorship curve ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Survivors ,Stage (cooking) ,skin and connective tissue diseases ,Aged ,Gynecology ,Medication use ,Aromatase inhibitor ,business.industry ,Aromatase Inhibitors ,Cancer-Free ,Women's Health Initiative ,Middle Aged ,medicine.disease ,Postmenopause ,Tamoxifen ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
While adverse medical sequelae are associated with breast cancer therapies, information on breast cancer impact on medication use is limited. Therefore, we compared medication use before and after diagnosis of early stage breast cancer to medication use in matched, cancer-free controls. Of 68,132 Women's Health Initiative participants, 3726 were diagnosed with breast cancer and, after exclusions, in 1731 breast cancer cases, medication use before and >3 years after diagnosis (mean 5.3 ± 2.1 SD) was compared to use in 1731 cancer-free matched controls on similar inventory dates. The medication category number at follow-up inventory was the primary study outcome. Medication category use (n, mean, SD) was comparable at baseline and significantly increased at follow-up in both cases (2.48 ± 1.66 vs. 4.15 ± 2.13, baseline vs follow-up, respectively, P < .0001) and controls (2.44 ± 1.67 vs. 3.95 ± 2.13, respectively, P < .0001), with clinically marginal but statistically significant additional medication category use by cases (0.20 ± 2.40, P < .0001). Tamoxifen users used somewhat more selected medication categories at follow-up assessment (mean 3.40 ± 1.89 vs. 3.21 ± 1.99, respectively, P = 0.05), while aromatase inhibitor users used more medication categories (mean 4.85 ± 2.10 vs. 4.44 ± 1.94, respectively, P = 0.02). No increase in medication category was seen in cases who were not current endocrine therapy users. Breast cancer survivors having only a clinically marginal increase in medication use compared to cancer-free controls. These findings highlight the importance of incorporation of control populations in studies of cancer survivorship.
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- 2016
46. Emerging combination endocrine therapies for advanced breast cancer
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Kathy Pan, Emily M. Lin, and Rowan T. Chlebowski
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Oncology ,medicine.medical_specialty ,Everolimus ,business.industry ,Advanced breast ,Endocrine therapy ,Cancer ,Ribociclib ,Palbociclib ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,Internal Medicine ,medicine ,Endocrine system ,Surgery ,030212 general & internal medicine ,business ,medicine.drug - Published
- 2017
47. Association of Low-Fat Dietary Pattern With Breast Cancer Overall Survival
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Michael S. Simon, Ross L. Prentice, Garnet L. Anderson, Dorothy S. Lane, JoAnn E. Manson, Lihong Qi, Aaron K. Aragaki, Linda Snetselaar, Rowan T. Chlebowski, Thomas E. Rohan, Marcia L. Stefanic, Marian L. Neuhouser, and Kathy Pan
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Male ,Cancer Research ,medicine.medical_specialty ,Diet therapy ,Breast Neoplasms ,Lower risk ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,Risk Factors ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Survival analysis ,Aged ,business.industry ,Women's Health Initiative ,Hazard ratio ,Correction ,Cancer ,Middle Aged ,medicine.disease ,Dietary Fats ,Survival Analysis ,Diet ,Oncology ,030220 oncology & carcinogenesis ,Women's Health ,Female ,business ,Diet Therapy - Abstract
Importance In a randomized clinical trial, a low-fat eating pattern was associated with lower risk of death after breast cancer. However, the extent to which results were driven by dietary influence on survival after breast cancer diagnosis was unknown. Objective To determine the association of a low-fat dietary pattern with breast cancer overall survival (breast cancer followed by death from any cause measured from cancer diagnosis). Design, Setting, and Participants This is a secondary analysis of the Women’s Health Initiative randomized clinical trial that was conducted at 40 US clinical centers enrolling participants from 1993 through 1998. Participants were 48 835 postmenopausal women with no previous breast cancer and dietary fat intake of greater than 32% by food frequency questionnaire. Interventions Participants were randomized to a dietary intervention group (40%; n = 19 541) with goals to reduce fat intake to 20% of energy and increase fruit, vegetable, and grain intake or a usual-diet comparison group (60%; n = 29 294). Dietary group participants with incident breast cancers continued to participate in subsequent dietary intervention activities. Main Outcomes and Measures Breast cancer overall survival for incident breast cancers diagnosed during the 8.5-year (median) dietary intervention, examined in post hoc analyses after 11.5 years (median) postdiagnosis follow-up. Results Of 1764 women diagnosed with breast cancer during the dietary intervention period, mean (SD) age at screening was 62.7 (6.7) years and age at diagnosis was 67.6 (6.9) years. With 516 total deaths, breast cancer overall survival was significantly greater for women in the dietary intervention group than in the usual-diet comparison group (10-year survival of 82% and 78%, respectively; hazard ratio [HR], 0.78; 95% CI, 0.65-0.94; P = .01). In the dietary group there were fewer deaths from breast cancer (68 vs 120; HR, 0.86; 95% CI, 0.64-1.17), other cancers (36 vs 65; HR, 0.76; 95% CI, 0.50-1.17), and cardiovascular disease (27 vs 64; HR, 0.62; 95% CI, 0.39-0.99). Conclusions and Relevance In women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased overall survival. The increase is due, in part, to better survival from several causes of death. Trial Registration ClinicalTrials.gov Identifier:NCT00000611
- Published
- 2018
48. Abstract 4944: Insulin resistance and long-term cancer-specific and all-cause mortality: The Women's Health Initiative (WHI)
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Joanne E. Mortimer, Arti Hurria, Rami Nassir, Gloria Y.F. Ho, JoAnn E. Manson, Jean Wactawski-Wende, Thomas E. Rohan, Rowan T. Chlebowski, Nazmus Saquib, Aladdin H. Shadyab, Jinnie J. Rhee, Rebecca A. Nelson, Lawrence S. Phillips, Kathy Pan, and Delphine J. Lee
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Cancer Research ,medicine.medical_specialty ,Insulin resistance ,Oncology ,business.industry ,Internal medicine ,Women's Health Initiative ,Medicine ,Cancer ,business ,medicine.disease ,All cause mortality ,Term (time) - Abstract
Background: Elevated insulin resistance has been associated with multiple morbid conditions. To our review, only one cohort study has evaluated insulin resistance and all-cause mortality in a general population (Pyorala 2000). Objective: To examine associations of insulin resistance with long-term cancer-specific and all-cause mortality in postmenopausal women. Methods: Included were 22,837 postmenopausal women aged 50-79 from the WHI cohort without prior cancer and with available fasting glucose and insulin levels. Using multivariate Cox proportional hazard models, we compared cancer-specific and all-cause mortality across quartiles of insulin resistance estimated by the homeostasis model assessment-insulin resistance (HOMA-IR) index. Results: Women in the highest HOMA-IR quartile were less educated, had higher BMI and waist circumference, were more likely to be Black, and were more likely to have hypertension than those in lower HOMA-IR quartiles. Women in the highest quartile were also significantly more likely to have a history of treated diabetes than those in lower quartiles (23.5% in Q4 versus 0.6% in Q1). After a median follow-up of 18.1 years, cancer-specific and all-cause mortality were significantly higher in the highest HOMA-IR quartile compared to the lowest (HR 1.25, 95% CI 1.07-1.46 and HR 1.62, 95% CI 1.50-1.75, respectively) (Table 1). In a sensitivity analysis excluding women with treated diabetes (remaining n=21,104), all-cause mortality findings were similar (HR 1.36, 95% CI 1.25-1.48, p Conclusion: Insulin resistance by HOMA-IR index identifies a substantial, previously under-recognized population of postmenopausal women at increased risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention. Table 1. Adjusted* HRs for cancer-specific and all-cause mortality by HOMA-IR quartilesHOMA-IR QuartilesNCancer Specific Mortality HR (95% CI) P valueAll Cause Mortality HR (95% CI) P valueQ1: 0.04-1.0857071.0 (reference)0.04311.0 (reference) Citation Format: Kathy Pan, Rebecca Nelson, Jean Wactawski-Wende, Delphine J. Lee, JoAnn E. Manson, Joanne E. Mortimer, Lawrence S. Phillips, Thomas Rohan, Gloria Y. Ho, Nazmus Saquib, Aladdin H. Shadyab, Rami Nassir, Jinnie J. Rhee, Arti Hurria, Rowan T. Chlebowski. Insulin resistance and long-term cancer-specific and all-cause mortality: The Women's Health Initiative (WHI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4944.
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- 2018
49. Unexplained dyspnea linked to mitochondrial myopathy following military deployment to Southwest Asia and Afghanistan
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Claudia Daniela Onofrei, Eva Brigitte Gottschall, Lauren Zell‐Baran, Cecile Stephanie Rose, Richard Kraus, Kathy Pang, and Silpa Dhoma Krefft
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Afghanistan ,cardiopulmonary exercise testing ,deployment ,dyspnea ,Iraq ,mitochondrial myopathy ,Physiology ,QP1-981 - Abstract
Abstract We identified a case of probable mitochondrial myopathy (MM) in a soldier with dyspnea and reduced exercise tolerance through cardiopulmonary exercise testing (CPET) following Southwest Asia (SWA) deployment. Muscle biopsy showed myopathic features. We compared demographic, occupational exposure, and clinical characteristics in symptomatic military deployers with and without probable MM diagnosed by CPET criteria. We evaluated 235 symptomatic military personnel who deployed to SWA and/or Afghanistan between 2010 and 2021. Of these, 168 underwent cycle ergometer maximal CPET with an indwelling arterial line. We defined probable MM based on five CPET criteria: arterial peak exercise lactate >12 mEq/L, anaerobic threshold (AT) ≤50%, maximum oxygen consumption (VO2max)
- Published
- 2023
- Full Text
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