Advancing Cancer Workforce Capacity for American Indians and Alaska Natives: The Development of a Validated System to Optimize Trainee Participation and Outcome Tracking.

Although American Indian and Alaska Native (AIAN) students are the most underrepresented group in the U.S. in biomedical and health sciences relative to population size, little is known about long-term research education programs and outcome tracking. For over 20 years, the Partnership for Native American Cancer Prevention (NACP) has been supported under the National Cancer Institute's (NCI)-funded Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) program. Programming included hands-on mentored research and an array of development opportunities. A validated tracking system combining participation records, institutional records, and enrollment/degree attainment from the National Student Clearinghouse documents outcomes. Collectively (2002-2022) NACP engaged 367 AIAN trainees, of whom 237 individuals earned 220 bachelors, 87 masters, and 34 doctoral/professional degrees. Approximately 45% of AIAN doctoral recipients are currently engaged in academic or clinical work, and 10% in industry or tribal leadership. A total of 238 AIAN students participated in mentored research, with 85% demonstrating strong outcomes; 51% attained a degree, and 34% are currently enrolled. Implementation of a robust tracking system documented acceleration in degree attainment over time. Next steps will evaluate the most impactful training activities on student outcomes.

Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

Health Behavior Change Intervention Preferences Expressed by American Indian Cancer Survivors From a Southwest Tribal Community: Semistructured Interview Study.

BACKGROUND: While many factors, including social determinants of health, affect cancer mortality, one modifiable risk factor that may contribute to cancer disparities is obesity. The prevalence of obesity in the American Indian/Alaska Native population is 48.1% per the Centers for Disease Control and Prevention. The overall cancer mortality for the American Indian/Alaska Native population is 18% higher than the White population as reported by the American Cancer Society. Interventions tailored to American Indian/Alaska Native communities that promote healthy lifestyle behaviors after cancer diagnosis and prior to cancer surgery (prehab) might improve cancer outcomes for this population. OBJECTIVE: The aim of the study is to characterize the lifestyle behaviors of San Carlos Apache cancer survivors and identify preferences for the adaption of a prehab intervention. METHODS: Semistructured interviews and validated questionnaires were completed with San Carlos Apache cancer survivors (N=4), exploring their viewpoints on healthy lifestyle and cancer risk and preferences for program development. A thematic content analysis was conducted. RESULTS: Participants had an average BMI of 31 kg/m2 and walked 53 minutes daily. The majority of participants reported a high willingness to change eating habits (n=3, 75%). All 4 reported willingness to participate in a diet and exercise program. Important themes and subthemes were identified: (1) cancer is perceived as a serious health condition in the community (N=4, 100%); (2) environmental exposures are perceived as cancer-causing threats (n=3, 75%); (3) healthy diet, exercise, and avoiding harmful substances are perceived as mitigating cancer risk (n=3, 75%); (4) barriers to healthy habits include distance to affordable groceries (n=3, 75%) and lack of transportation (n=2, 50%); (5) there is high interest in a prehab program geared toward patients with cancer (N=4, 100%); and (6) standard monitoring practiced in published prehab programs showed early acceptability with participants (N=4, 100%). CONCLUSIONS: Collaboration with tribal partners provided important insight that can help inform the adaptation of a culturally appropriate prehab program for San Carlos Apache patients diagnosed with cancer.

Restoring Balance: a physical activity intervention for Native American cancer survivors and their familial support persons.

Introduction/Purpose: Exercise interventions among Native American cancer survivors are lacking, despite major cancer health disparities in survivorship. The purpose of this study was to evaluate a 12-week randomized controlled trial (RCT) of culturally tailored exercise on cancer risk biomarkers and quality of life among Native American cancer survivors and family members. Methods: Participants were randomized to immediate start versus 6-week waitlist control at two rural and two urban sites. Participants enrolled in a small feasibility pilot study (only cancer survivors evaluated, n=18; cohort 1) or larger efficacy pilot study where cancer survivors (n=38; cohort 2) and familial supporters (n=25; cohort 3) were evaluated concurrently. Resistance, aerobic, flexibility, and balance exercises were tailored by cultural experts representing ten tribes. Exercises was supervised on-site one day per week and continued in home-based settings two to five days per week. Fat mass, blood pressure, hemoglobin A1c, 6-min walk, sit-to-stand test, and quality of life (Patient-Reported Outcomes Measurement Information System Global Health short form and isolation subscale) were measured. Mixed effects models evaluated differences between RCT arms from baseline to 6 weeks, and 12-week intervention effects in combined arms. Results: There were no consistent differences at 6 weeks between randomized groups. Upon combining RCT arms, 6-min walk and sit-to-stand tests improved in all three cohorts by 12 weeks (both survivors and familial support persons, p<0.001); social isolation was reduced in all three cohorts (p≤0.05). Familial support persons additionally improved blood pressure and HbA1c (p≤0.05). Conclusion: Exercise improved cardiorespiratory fitness and physical function among Native American cancer survivors and familial supporters. A longer intervention may influence other important health outcomes among Native American survivors. Additional improvements demonstrated among Native American family members may have a meaningful impact on cancer prevention in this underserved population with shared heritable and environmental risks.

Characterization and efficacy of lifestyle behavior change interventions among adult rural cancer survivors: a systematic review.

PURPOSE: Little is known about the intersection between age and rurality as characteristics that impact lifestyle behavior change for cancer survivors. This review aims to summarize the current literature on lifestyle behavior change interventions conducted among rural survivors of cancer, with an emphasis on older survivors. METHODS: A systematic search of five databases identified randomized controlled trials and controlled clinical trials that targeted diet, physical activity, alcohol consumption, or tobacco use change in adult cancer survivors living in rural areas of the world. RESULTS: Eight studies met the inclusion criteria. Most studies were conducted in either Australia or the USA, included survivors at least 6 weeks post-treatment, and half included only breast cancer survivors, while the other four included a mix of cancer types. All but one had a physical activity component. No articles addressed changes in alcohol or tobacco behavior. Seven (87.5%) had a fully remote or hybrid delivery model. Most of the physical activity interventions showed significant changes in physical activity outcomes, while the dietary interventions showed changes of clinical but not statistical significance. CONCLUSIONS: Few studies have been conducted to implement and evaluate the effectiveness of lifestyle behavior change interventions among older rural survivors of cancer. Future research should evaluate the acceptability and relevancy of adapted, evidence-based intervention with this population. IMPLICATIONS FOR CANCER SURVIVORS: Effective diet and physical activity interventions exist, albeit limited in terms of effective lifestyle behavior change intervention tailored to older, rural survivors of cancer, particularly in relation to alcohol and tobacco behaviors.

Dietary Supplement Use in Women Diagnosed with Breast Cancer.

BACKGROUND: Vitamins, minerals, and natural product (NP)-derived dietary supplements are commonly used among women with breast cancer, where interactions with treatments and the disease are possible, emphasizing the importance for health care providers to be aware of supplement use. OBJECTIVES: The study aimed to investigate current vitamin/mineral (VM) and NP supplement use among those diagnosed with breast cancer, including usage based on tumor type or concurrent breast cancer treatments and primary information sources for specific supplements. METHODS: Social media recruiting to complete an online questionnaire self-reporting current VM and NP use and breast cancer diagnosis and treatment information primarily attracted US participants. Analyses, including multivariate logistic regression, were performed on 1271 women who self-reported breast cancer diagnosis and completed the survey. RESULTS: Most participants reported current VM (89.5%) and NP (67.7%) use, with 46.5% (VM) and 26.7% (NP) using at least 3 products concurrently. Top-reported (>15% prevalence) products were vitamin D, calcium, multivitamin, and vitamin C for VM and probiotics, turmeric, fish oil/omega-3 fatty acids, melatonin, and cannabis for NP. Overall, VM or NP use was higher among those with hormone receptor-positive tumors. Although overall NP use did not differ according to current breast cancer treatments, VM use was significantly less common among those currently undergoing chemotherapy or radiation, but higher with current endocrine therapy. Among current chemotherapy users, specific VM and NP supplements with possible adverse effects were still used by 23% of respondents. Medical providers were the primary information source for VM, whereas NP information sources were more varied. CONCLUSIONS: Because women diagnosed with breast cancer commonly reported concurrent use of multiple VM and NP supplements, including those with known or underexplored risks (or benefits) in breast cancer, it is important for health care providers to inquire about and facilitate discussions regarding supplement use in this population.

Longitudinal patterns of abdominal visceral and subcutaneous adipose tissue, total body composition, and anthropometric measures in postmenopausal women: Results from the Women's Health Initiative.

BACKGROUND: Abdominal adiposity, including visceral and subcutaneous abdominal adipose tissue (VAT and SAT), is recognized as a strong risk factor for cardiometabolic disease, cancer, and mortality. OBJECTIVE: The primary aim of this analysis is to describe longitudinal patterns of change in abdominal adipose tissue in postmenopausal women, overall and stratified by age, race/ethnicity, and years since menopause. METHODS: The data are from six years of follow up on 10,184 postmenopausal women (7828 non-Hispanic White women, 1423 non-Hispanic Black women, and 703 Hispanic women) who participated in the Women's Health Initiative (WHI). The WHI is a large prospective cohort study of postmenopausal women across the United States. All participants in this analysis had DXA scans in the 1990s as part of the WHI protocol. Hologic APEX software was used to re-analyze archived DXA scans and obtain measures of abdominal adipose tissue. Analyses examined differences in abdominal adipose tissue, overall adiposity, and anthropometric variables. RESULTS: There were important differences in VAT and SAT by age and race/ethnicity. In women <60 years, VAT increased over the follow-up period, while in women ≥70 years, VAT decreased. Non-Hispanic Black women had the highest levels of SAT. Hispanic women had the highest VAT levels. Women more than ten years since menopause had less SAT and more VAT than women less than ten years since menopause, resulting in a higher VAT/SAT ratio. There was a moderate to strong correlation between measures of abdominal adipose tissue and anthropometric measurements of body size. Still, there were substantial differences in the quantity of VAT and SAT within BMI and waist circumference categories. CONCLUSIONS: These results demonstrate differences in VAT and SAT according to age, race/ethnicity, time since menopause, and compared to standard measures of body composition in a large and diverse cohort of postmenopausal women.

Prioritizing rural populations in state comprehensive cancer control plans: a qualitative assessment.

PURPOSE: The Centers for Disease Control and Prevention's National Comprehensive Cancer Control Program (NCCCP) requires that states develop comprehensive cancer control (CCC) plans and recommends that disparities related to rural residence are addressed in these plans. The objective of this study was to explore rural partner engagement and describe effective strategies for incorporating a rural focus in CCC plans. METHODS: States were selected for inclusion using stratified sampling based on state rurality and region. State cancer control leaders were interviewed about facilitators and barriers to engaging rural partners and strategies for prioritizing rural populations. Content analysis was conducted to identify themes across states. RESULTS: Interviews (n = 30) revealed themes in three domains related to rural inclusion in CCC plans. The first domain (barriers) included (1) designing CCC plans to be broad, (2) defining "rural populations," and (3) geographic distance. The second domain (successful strategies) included (1) collaborating with rural healthcare systems, (2) recruiting rural constituents, (3) leveraging rural community-academic partnerships, and (4) working jointly with Native nations. The third domain (strategies for future plan development) included (1) building relationships with rural communities, (2) engaging rural constituents in planning, (3) developing a better understanding of rural needs, and (4) considering resources for addressing rural disparities. CONCLUSION: Significant relationship building with rural communities, resource provision, and successful strategies used by others may improve inclusion of rural needs in state comprehensive cancer control plans and ultimately help plan developers directly address rural cancer health disparities.

Follicle-stimulating hormone is associated with low bone mass in postmenopausal women.

We evaluated the influence of two endogenous hormones on bone health in older women. Higher FSH was associated with bone disease, especially in lower estradiol environments. FSH attenuated the relationship between estradiol and bone. This may provide a mechanism through which future clinical research intervenes on bone loss. INTRODUCTION/PURPOSE: Despite preclinical evidence for an inverse association of follicle-stimulating hormone (FSH) and bone mineral density (BMD), no large epidemiologic studies have evaluated the separate and joint influences of FSH and estradiol on bone in postmenopausal women. METHODS: In a cross-sectional study of 675 postmenopausal women, we evaluated associations of serum FSH and dual X-ray absorptiometry (DXA)-classified areal BMD as well as low bone mass or osteoporosis (T-score < - 1.0) of the femoral neck and total hip. We stratified this analysis by serum estradiol (cut at the median). We tested whether FSH mediates the association of estradiol and BMD using the Sobel test. RESULTS: In linear regression models, there was a significant inverse association of serum FSH with both femoral neck and total hip BMD (both p < 0.01) when adjusted for age, hormone therapy (HT) use, and diabetes. In fully adjusted logistic regression models, women in the highest FSH tertile had higher odds of low bone mass/osteoporosis at the femoral neck (OR = 2.98; 95% CI = 1.86-4.77) and at the total hip (OR = 1.74; 95% CI = 1.06-2.84) compared to those in the lowest FSH tertile. We report evidence of effect modification by estradiol in stratified models and an interaction term. FSH met all criteria of a mediator, including an estimated 70% attenuation of the estradiol-BMD relationship (Sobel p value < 0.001). CONCLUSIONS: FSH is associated with higher odds of having low bone mass/osteoporosis even after accounting for HT use. FSH is a mediator of the relationship between estradiol and BMD in healthy postmenopausal women. Larger, prospective studies of FSH concentrations and bone health are needed.

Association of ß-glucuronidase activity with menopausal status, ethnicity, adiposity, and inflammation in women.

OBJECTIVES: Many dietary polyphenols with potential health-promoting benefits undergo hepatic conjugation and circulate as inactive glucuronides that can be cleaved by ß-glucuronidase to reform the bioactive aglycone. Although indirect evidence suggests estrogen may induce ß-glucuronidase, little is known about ß-glucuronidase regulation across women's reproductive lifespan. Correlates of serum ß-glucuronidase activity in healthy premenopausal versus postmenopausal women were therefore examined. METHODS: ß-Glucuronidase activity and C-reactive protein (CRP) were assayed in stored serum from the Women's Breast and Bone Density Study, and dual-energy x-ray absorptiometry and anthropometry assessed body composition. Participants were premenopausal (n = 133) or postmenopausal (n = 89), and Hispanic (37%) or non-Hispanic White (63%). Multivariate linear regression models tested associations between ß-glucuronidase and menopausal status, ethnicity, CRP, and body composition metrics, overall and stratified by menopausal status. RESULTS: Postmenopausal (vs premenopausal) women were older (60.4 ± 3.7 vs 44.8 ± 2.4 y) with a lower Hispanic ethnicity prevalence (27% vs 44%), and higher serum ß-glucuronidase activity (1.5 ± 0.8 vs 1.3 ± 0.5 U/L) and CRP (4.2 ± 4.4 vs 3.3 ± 4.7 mg/L). Adjusting for confounders, ß-glucuronidase was positively associated with Hispanic ethnicity, CRP, body mass index, and total fat mass (all, P < 0.01), but not menopausal status nor lean mass. Central adiposity measures were also positively associated with ß-glucuronidase with the same covariates. CONCLUSIONS: ß-Glucuronidase enzyme activity, upon which polyphenol health-related benefits may depend, is not associated with menopausal status. Future studies are required to determine clinical significance and mechanisms driving ß-glucuronidase associations with ethnicity, inflammation, and adiposity in women.

Formative Evaluation and Adaptation of a Navajo Cancer Survivor Physical Activity Intervention to Serve a Broader Native American Cancer Survivor Community.

BACKGROUND: Although exercise has been shown to improve cancer survivorship in other communities, cancer exercise studies among Native American communities are rare. We sought to adapt a Navajo-tailored cancer exercise pilot program to serve a broader Native American cancer community. METHODS: Tribal experts representing 10 different Tribal Nations were engaged in small focus groups (n=2-4) to assess program materials for cultural appropriateness and adaptation to expand tribal inclusiveness. Facilitated by a trained Native American interviewer, focus groups were provided a primer survey and then reviewed intervention materials (protocols, incentives, logo, flyers, etc.). Consensus was reached by the research team on all program adaptations. RESULTS: The program name, Restoring Balance, layout, graphics, and symbols were considered culturally appropriate overall. Program exercises and biomarker measurements were viewed as valuable to health improvements in the community. Important color, linguistic, and logistic program modifications were recommended to improve cultural alignment. The order of incentive items was revised to highlight restoration and the logo rotated to align with the four corners of the earth, an important cultural element. Linguistic modifications primarily related to prior traumatic research experiences in Native American communities where data had been taken without adequate community benefit or permission. Program emphasis should be on nurturing, added value and giving. CONCLUSION AND RELEVANCE: The methodology used for cultural expert review was successful in eliciting adaptations to expand the tribal inclusiveness of Restoring Balance. Culture, as well as historically traumatic research experiences, among Native American populations must be considered when adapting health promotion programming.

Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants.

BACKGROUND: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI). METHODS: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking. RESULTS: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification. CONCLUSIONS: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality. LAY SUMMARY: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.

Physical Activity in Young BRCA Carriers and Reduced Risk of Breast Cancer.

INTRODUCTION: A systematic literature review was conducted to determine whether physical activity levels during adolescent and young adult years were associated with a reduced lifetime risk of breast cancer among carriers of deleterious mutations in BRCA1 and BRCA2 genes. METHODS: Ovid/MEDLINE, Embase, CENTRAL, WOS, and CINAHL were searched for articles including information about adolescent and young adult physical activity and breast cancer incidence among women carrying deleterious BRCA1 and BRCA2 gene mutations (search was initiated in October 2019; last update and full analyses were in March 2021). Independent reviewers screened articles at the title/abstract and full-text levels, resolving differences by consensus with lead authors. The NIH Quality Assessment Tools were used to assess sources of bias. RESULTS: A total of 1,957 unique articles were identified; 5 met inclusion criteria. Samples size ranged from 68 to 1,185. All studies relied on self-reported adolescent and young adult physical activity. One study measured sports involvement; the others measured recreational activity. One large study was null, whereas 4 others showed a reduction in breast cancer incidence later in life with higher adolescent and young adult physical activity (p≤0.05). However, the protection was limited to premenopausal breast cancer in 1 of the studies (OR=0.62; 95% CI=0.40, 0.96; p-trend=0.01). In addition, adolescent and young adult physical activity was associated with older age at breast cancer diagnosis in 1 study (p=0.03). CONCLUSIONS: A limited number of studies suggest that adolescent and young adult physical activity may reduce or delay the risk of breast cancer incidence among carriers of deleterious mutations in BRCA1 and BRCA2 genes.

Serum Follicle-Stimulating Hormone and 5-Year Change in Adiposity in Healthy Postmenopausal Women.

CONTEXT: Evidence from animal studies suggests that the gradual rise in follicle-stimulating hormone (FSH) during reproductive senescence may contribute to the change in adiposity distribution characteristic of menopause. The potential independent role the interrelationships of FSH and estradiol (E2) may play in postmenopausal adiposity changes are not well studied. OBJECTIVE: Our objective was to evaluate the associations of FSH and dual x-ray absorptiometry (DXA)-derived adiposity measures, with consideration of estradiol and postmenopausal hormone therapy use. METHODS: In a sample of 667 postmenopausal women from the Women's Health Initiative Buffalo OsteoPerio Ancillary Study, we studied the associations of serum FSH and E2 levels with dual x-ray absorptiometry (DXA)-derived adiposity measures via cross-sectional and longitudinal analyses (5-year follow-up). RESULTS: In cross-sectional analyses, FSH levels were inversely associated with all measures of adiposity in models adjusted for age, years since menopause, smoking status, pack-years, and hormone therapy (HT) use; these associations were not influenced by adjustment for serum E2. In longitudinal analyses, the subset of women who discontinued HT over follow-up (n = 242) experienced the largest increase in FSH (+33.9 mIU/mL) and decrease in E2 (-44.3 pg/mL) and gains in all adiposity measures in unadjusted analyses. In adjusted analyses, an increase in FSH was associated with a gain in percentage of total body fat, total body fat mass, and subcutaneous adipose tissue (SAT). CONCLUSION: While cross-sectional findings suggest that FSH is inversely associated with adiposity, our longitudinal findings suggest that greater increases in FSH were associated with greater increases in percentage of total body fat, total body fat mass, and SAT. Future studies are needed to provide additional insight into FSH-adiposity mechanisms in larger samples.

Association of Lower Extremity Lymphedema With Physical Functioning and Activities of Daily Living Among Older Survivors of Colorectal, Endometrial, and Ovarian Cancer.

Importance: Lower extremity lymphedema (LEL) is associated with decreased physical functioning (PF) and activities of daily living (ADLs) limitations. However, the prevalence of LEL in older survivors of cancer is unknown. Objectives: To examine LEL among older female survivors of colorectal, endometrial, or ovarian cancer and investigate the association of LEL with PF and ADLs. Design, Setting, and Participants: This secondary analysis of the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study was conducted using data from postmenopausal women enrolled at 40 US centers. Participants were women who had a prior diagnosis of endometrial, colorectal, or ovarian cancer and who had completed the WHI LILAC baseline and year 1 follow-up questionnaires as of September 2017. Exposures: The 13-item Lower Extremity Lymphedema Screening Questionnaire in Women was used to determine LEL (ie, score ≥5). Main Outcomes and Measures: Validated surveys were used to assess PF and ADLs. Results: Among 900 older women diagnosed with endometrial, colorectal, or ovarian cancer, the mean (SD) age was 78.5 (5.9) years and the mean (range) time since cancer diagnosis was 8.75 (1.42-20.23) years. Overall, 292 women (32.4%) reported LEL, with the highest LEL prevalence among survivors of ovarian cancer (38 of 104 women [36.5%]), followed by survivors of endometrial cancer (122 of 375 women [32.5%]) and colorectal cancer (132 of 421 women [31.4%]). Compared with women without LEL, women with LEL had a PF score that was lower by a mean (SE) 16.8 (1.7) points (P < .001) and higher odds of needing help with ADLs (odds ratio [OR], 2.45; 95% CI, 1.64-3.67). In the association of LEL with PF, the mean (SE) decrease in PF score was greatest among survivors of colorectal cancer (-21.8 [2.6]) compared with survivors of endometrial cancer (-13.3 [2.7]) and ovarian cancer (-12.8 [5.2]). Additionally, among survivors of colorectal cancer, LEL was associated with increased odds of needing help with ADLs (OR, 3.59; 95% CI, 1.94-6.66), while there was no such association among survivors of endometrial cancer or ovarian cancer. However, there were no interaction associations between LEL and cancer type for either outcome. Additionally, the overall mean (SE) difference in PF between women with and without LEL was greater among those aged 80 years and older (-19.4 [2.6] points) vs those aged 65 to 79 years (-14.9 [2.2] points). However, among survivors of colorectal cancer, the mean (SE) difference in PF score was greater among women aged 65 to 79 years (-22.9 [3.7] points) vs those aged 80 years or older (-20.8 [3.7] points) (P for 3-way interaction = .03). Conclusions and Relevance: This study found that nearly one-third of older female survivors of colorectal, endometrial, or ovarian cancer experienced LEL and that LEL was associated with decreased PF and increased odds of needing help with ADLs. These findings suggest that clinicians may need to regularly assess LEL among older survivors of cancer and provide effective interventions to reduce LEL symptoms and improve PF for this population.

Correlates of physical activity among older breast cancer survivors: Findings from the Women's Health Initiative LILAC study.

INTRODUCTION: Physical activity can attenuate cancer-related declines in physical functioning, improve emotional well-being, and prolong survival among older (≥65 years) breast cancer survivors. However, factors associated with physical activity among older breast cancer survivors are not well-understood. MATERIALS AND METHODS: Participants were enrolled in the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study. Descriptive statistics, multiple linear regression, and relative risk [RR] regression were used to assess the association of demographic, clinical, physical and psychosocial variables with the total duration of and participation in physical activity among postmenopausal breast cancer survivors. Age-specific correlates (65-74 years vs. 75-84 years vs. ≥85 years) of physical activity were also examined. RESULTS: The majority of participants (n = 3710, mean age = 78.8 ± 5.9) were white (90.7%) and had in situ/localized breast cancer (78.9%). Women who had higher education (RR = 1.47 for graduate/professional school versus high school or less, 95% CI: 1.32, 1.63), higher self-rated health (RR = 1.04 for 10 point increase, 95% CI:1.02, 1.07), higher physical functioning (RR = 1.03 for 5 point increase, 95% CI: 1.02, 1.04), and higher social support (RR = 1.41 for social support all of the time versus none of the time, 95% CI: 1.01, 1.96), were more likely to engage in any physical activity. Similar results were observed for duration of physical activity. Among women aged <75, radiation therapy, but not chemotherapy, was associated with longer duration of total physical activity (adjusted difference = 19.7 min/week, 95% CI: 6.1, 33.3), but was not associated with duration among older women. The association between pain and duration of moderate/strenuous activity also differed with age: among women aged <75, those with moderate pain averaged fewer minutes of moderate/strenuous physical activity than those with no pain (adjusted difference:-14.4 min/week, 95% CI:-28.5, -0.1). However, among women aged ≥85, those with moderate pain averaged more minutes of moderate/strenuous physical activity per week than those with no pain (adjusted difference:16.6 min/week; 95% CI:2.9, 30.3). DISCUSSION: Multiple factors were associated with physical activity among older breast cancer survivors in the WHI. Future physical activity interventions should focus on age-related (e.g., comorbidities) and treatment-related factors (e.g., radiation) as well as certain subgroups, such as women with higher symptom burden.

Prevalence and predictors of peripheral neuropathy after breast cancer treatment.

BACKGROUND: Many of the 3.8 million breast cancer survivors in the United States experience long-term side effects of cancer therapy including peripheral neuropathy (PN). We assessed the prevalence and predictors of PN among women with breast cancer followed in the Women's Health Initiative's Life and Longevity After Cancer survivorship cohort. METHODS: The study population included 2420 women with local (79%) or regional (21%) stage disease. Presence of PN was based on the reports of "nerve problems and/or tingling sensations" after treatment and PN severity was assessed using the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity instrument. Logistic regression analysis was used to evaluate the socio-demographic and clinical factors associated with PN prevalence and severity. RESULTS: Initial breast cancer treatment included surgery-only (21%), surgery and radiation (53%), or surgery and chemotherapy (±radiation) (26%). Overall, 17% of women reported PN occurring within days (30%), months (46%), or years (24%) after treatment and 74% reported ongoing symptoms at a median of 6.5 years since diagnosis. PN was reported by a larger proportion of chemotherapy recipients (33%) compared to those who had surgery alone (12%) or surgery+radiation (11%) (p < 0.0001). PN was reported more commonly by women treated with paclitaxel (52%) and docetaxel (39%), versus other chemotherapy (17%) (p < 0.0001). In multivariable analyses, treatment type (chemotherapy vs. none; OR, 95% CI: 3.31, 2.4-4.6), chemotherapy type (taxane vs. no-taxane; 4.74, 3.1-7.3), and taxane type (paclitaxel vs. docetaxel; 1.59, 1.0-2.5) were associated with higher odds of PN. CONCLUSION: PN is an important long-term consequence of taxane-based chemotherapy in breast cancer survivors.

Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

BACKGROUND: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. METHODS: Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. RESULTS: Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17ß diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. CONCLUSIONS: Current BMI is associated with androgen metabolism among postmenopausal women. IMPACT: This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.

Association of Sedentary Time and Incident Heart Failure Hospitalization in Postmenopausal Women.

BACKGROUND: The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB's role in heart failure (HF) is unclear. METHODS: We studied 80 982 women in the Women's Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline. Mean follow-up was 9 years for physician-adjudicated incident HF hospitalization (1402 cases). SB was assessed repeatedly by questionnaire. Time-varying total SB was categorized according to awake time spent sitting or lying down (≤6.5, 6.6-9.5, >9.5 h/d); sitting time (≤4.5, 4.6-8.5, >8.5 h/d) was also evaluated. Hazard ratios and 95% CI were estimated using Cox regression. RESULTS: Controlling for age, race/ethnicity, education, income, smoking, alcohol, menopausal hormone therapy, and hysterectomy status, higher HF risk was observed across incremental tertiles of time-varying total SB (hazard ratios [95% CI], 1.00 [referent], 1.15 [1.01-1.31], 1.42 [1.25-1.61], trend P<0.001) and sitting time (1.00 [referent], 1.14 [1.01-1.28], 1.54 [1.34-1.78], trend P<0.001). The inverse trends remained significant after further controlling for comorbidities including time-varying myocardial infarction and coronary revascularization (hazard ratios: SB, 1.00, 1.11, 1.27; sitting, 1.00, 1.09, 1.37, trend P<0.001 each) and for baseline physical activity (hazard ratios: SB 1.00, 1.10, 1.24; sitting 1.00, 1.08, 1.33, trend P<0.001 each). Associations with SB exposures were not different according to categories of baseline age, race/ethnicity, body mass index, physical activity, physical functioning, diabetes, hypertension, or coronary heart disease. CONCLUSIONS: SB was associated with increased risk of incident HF hospitalization in postmenopausal women. Targeted efforts to reduce SB could enhance HF prevention in later life.