Cancer Prevention Scientific Publications

The Breast Cancer Weight Loss trial (Alliance A011401): A description and evidence for the lifestyle intervention

Obesity (Silver Spring)

2022 Marian Neuhouser

The Breast Cancer Weight Loss (BWEL) trial is a randomized controlled trial designed to determine whether weight loss after a breast cancer diagnosis can reduce the risk of cancer recurrence in women with overweight or obesity. The BWEL trial will compare the efficacy of a telephone-based weight-loss intervention plus health education materials versus health education materials alone on invasive disease-free survival in 3,181 women with stage II or III breast cancer and BMI > 27 kg/m2 . This report provides a detailed description of the goals and methods of the lifestyle intervention and the evidence supporting the intervention used in the BWEL trial. The intervention's primary goal for participants is to achieve and maintain a weight loss ≥ 10% of baseline weight through increased physical activity and caloric restriction. The evidence supporting the diet, physical activity, and behavioral components of this telephone-based weight-loss intervention, as well as strategies to promote participant engagement and retention, is described. The intervention is provided through 42 sessions delivered by trained health coaches over a 2-year period. If the BWEL lifestyle intervention is successful in improving cancer outcomes, then weight loss will be incorporated into the care of thousands of breast cancer patients.

Associations between Genetic Variants and Blood Biomarkers of One-carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study

J Nutr

2021 Marian Neuhouser; Yingye Zheng; Xiaoling Song; Shirley Beresford

BACKGROUND: Genetic variation in one-carbon metabolism may affect nutrient levels and biological functions. However, data on genetic variants associated with blood biomarkers of one-carbon metabolism in U.S. postmenopausal women are limited, and whether these associations were affected by the nationwide folic acid (FA) fortification program is unclear. OBJECTIVE: We investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Women's Health Initiative Observational Study. METHODS: In 1,573 non-Hispanic White (NHW) and 282 Black/African American, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic/Latino women aged 50-79 years, 288 non-synonymous and tagging single-nucleotide variants (SNVs) were genotyped. Red blood cell (RBC) folate, plasma folate, pyridoxal-5'-phosphate (PLP), vitamin B-12, homocysteine, and cysteine levels were determined in 12-h fasting blood. Multivariable linear regression tested associations per variant allele and for an aggregated genetic risk score. Effect modifications before, during, and after nationwide FA fortification were examined. RESULTS: After correction for multiple comparisons, among NHW women, 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677CT) variant T was associated with lower plasma folate (-13.0%, 95% CI = -17.3% to -8.6%) and higher plasma homocysteine (3.5%, 95% CI = 1.7% to 5.3%) concentrations. Other associations for non-synonymous SNVs included DNMT3A rs11695471 (TA) with plasma PLP; EHMT2 rs535586 (GA), TCN2 rs1131603 (L349S AG) and TCN2 rs35838082 (R188W GA) with plasma vitamin B-12; CBS rs2851391 (GA) with plasma homocysteine; and MTHFD1 rs2236224 (GA) and rs2236225 (R653Q GA) with plasma cysteine. The influence of FA fortification on the associations was limited. Highest vs. lowest quartiles of aggregated genetic risk scores from SNVs in MTHFR and MTRR were associated with 14.8% to 18.9% lower RBC folate concentrations. Gene-biomarker associations were similar in women of other races/ethnicities. CONCLUSIONS: Our findings on genetic variants associated with several one-carbon metabolism biomarkers may help elucidate mechanisms of maintaining B vitamin status in postmenopausal women.

Fatigue in community-dwelling older adults: A review of definitions, measures, and related factors

Geriatr Nurs

2021 Kerryn Reding; Barbara Cochrane

Fatigue is a common age-related symptom among community-dwelling adults aged 65 years and older. Yet, a systematic approach has rarely been applied to review definitions, measures, related factors, and consequences of fatigue in this population. A scoping review was conducted in December 2020 to fill the gap, and 36 articles met the inclusion criteria. Definitions, albeit diverse, included at least one of the following attributes: an early indicator of disablement, subjective, a lack of energy, multidimensional, impaired daily activities, and temporal. A summary of fatigue measures used in this population was provided, including a brief overview, number of items, reliability, and validity. In general, different measures were used with considerable variability in the content. Additionally, most measures had limited information on test-retest reliability and validity. Fatigue-related factors mapped into biological, psychological, social, and behavioral factors. Fatigue consequences were primarily declines in physical and cognitive functions. (100-150 words).

The emerging role of real-world data in advanced breast cancer therapy: Recommendations for collaborative decision-making


2021 Scott Ramsey

Among stakeholders and decision-makers in advanced breast cancer, the demand for insights from real-world data (RWD) is increasing. Although RWD can be used to support decisions throughout different stages of a breast cancer drug's life cycle, barriers exist to its use and acceptance. We propose a collaborative approach to generating and using RWD that is meaningful to multiple stakeholders, and encourage frameworks toward international guidelines to help standardize RWD methodologies to achieve more efficient use of RWD insights.

Associations between changes in loneliness and social connections, and mental health during the COVID-19 Pandemic: The Women's Health Initiative

J Gerontol A Biol Sci Med Sci

2021 Lisa Johnson; Garnet Anderson; Roberta Ray

BACKGROUND: Older women have faced significant disruptions in social connections during the coronavirus disease 2019 pandemic. Whether loneliness increased, or whether a change in loneliness from pre- to intra-pandemic period was associated with mental health during the pandemic is unknown. METHODS: Older women (n=27,479; mean age 83.2 [SD: 5.4] years) completed surveys in mid-2020, including questions about loneliness, living arrangements, changes in social connections, and mental health. Loneliness was also previously assessed in 2014-2016. We examined whether loneliness changed from the pre- to intra-pandemic period and explored factors associated with this change. In multivariable models, we investigated the association of changes in loneliness and social connections with mental health. RESULTS: Loneliness increased from pre- to intra-pandemic levels. Factors associated with worsening loneliness included older age, experiencing stressful life events, bereavement, histories of vascular disease and depression, and social connection disruptions. Factors associated with a decrease in loneliness included identifying as Black, engaging in more frequent physical activity, being optimistic, and having a higher purpose in life. A 3-point increase in loneliness scores was associated with higher perceived stress, higher depressive, and higher anxiety symptoms. Social connection disruptions showed modest or no associations with mental health. CONCLUSIONS: Loneliness increased during the pandemic in older women and was associated with higher stress, depressive and anxiety symptoms. Our findings point to opportunities for interventions targeting lifestyle behaviors, well-being, disrupted social connections, and paying closer attention to those with specific medical and mental health histories that may reduce loneliness and improve mental health.

The impact of medical tourism on cervical cancer screening among immigrant women in the US

BMC Womens Health

2021 Linda Ko; Hendrika Meischke

BACKGROUND: Research on the relationship between medical tourism-traveling abroad for healthcare and cervical cancer screening is lacking. This study examines (1) the association between medical tourism and cervical cancer screening among immigrant women and (2) whether the association varies across years in the U.S. METHODS: We analyzed the New Immigrant Survey data of immigrant women aged 21-65 (n=999). The outcome was having had a Pap smear since becoming a permanent resident, and the main predictor was medical tourism. Logistic regressions were conducted. RESULTS: Immigrant women who engaged in medical tourism had higher cervical cancer screening rates compared to those who did not engage in medical tourism (84.09% vs. 71.68%). This relationship was statistically significant only among women who have recently immigrated, after controlling for covariates. CONCLUSIONS: Immigrant women who engaged in medical tourism had 2.18 higher odds of receiving a Pap smear than immigrant women who did not, after controlling for other covariates. Health educators should be aware of the practice of medical tourism and consider providing education on adherence to cancer screening guidelines and follow up abnormal results to ensure that immigrant women receive continuous cancer care.

Biomarker-based Methods and Study Designs to Calibrate Dietary Intake for Assessing Diet-Disease Associations

J Nutr

2021 Ross Prentice; Lesley Tinker; Ying Huang; Marian Neuhouser

BACKGROUND: Dietary biomarkers measured in biospecimens can play an important role in correcting for random and systematic measurement error in self-reported nutrient intake when assessing diet-disease associations. To date, high quality biomarkers for calibrating self-reported dietary intake have only been developed for a few nutrients. OBJECTIVE: To investigate new study designs and regression calibration approaches for calibrating self-reported nutrient intake for use in disease association analyses. METHODS: We studied three regression calibration approaches: (I) an existing approach built on a calibration cohort assuming the existence of an objective biomarker, i.e., biomarker with random independent measurement error, (II) a proposed approach utilizing a biomarker development cohort, and (III) a proposed two-stage approach utilizing both cohorts. We conducted simulation studies to compare performance of different study designs/methods for estimating diet-disease associations, and applied suitable methods to examine the association of sodium and potassium intake with cardiovascular disease (CVD) risk in Women's Health Initiative cohorts. RESULTS: Simulation studies showed that approach (I) can lead to biased association estimation when the objective biomarker assumption is violated; the proposed approaches (II) and (III) obviate the need for such an objective biomarker. Precision for estimating the association depends critically on sample size of the biomarker development cohort and the strength of the self-reported nutrient intake. Analyses based on approaches (II) and (III) support previously reported significant findings using approach (I) about associations of the ratio of sodium to potassium intake with CVD risk, while providing efficiency gain for some outcomes. CONCLUSIONS: Self-reported dietary intake needs to be calibrated for measurement error correction in diet-disease association analyses. When there are no existing objective biomarkers that can be used for calibration purpose, controlled feeding studies can be used to develop new biomarkers for use in calibration, or can be used to calibrate self-reported dietary intake directly.

Nrf2 plays a critical role in the metabolic response during and after spaceflight

Commun Biol

2021 Thomas Kensler

Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by Nrf2 knockout. We conducted metabolome analyses of plasma from wild-type and Nrf2 knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in Nrf2 knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of Nrf2 knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.

Analgesic use and circulating estrogens, androgens, and their metabolites in the Women's Health Initiative Observational Study

Cancer Prev Res (Phila)

2021 Garnet Anderson

Though studies have observed inverse associations between use of analgesics (aspirin, non-aspirin nonsteroidal anti-inflammatory drugs [NSAIDs], and acetaminophen) and the risk of several cancers, the potential biological mechanisms underlying these associations are unclear. We investigated the relationship between analgesic use and serum concentrations of estrogens, androgens, and their metabolites among postmenopausal women to provide insights on whether analgesic use might influence endogenous hormone levels, which could in turn influence hormone-related cancer risk. The study included 1,860 postmenopausal women from two case-control studies nested within the Women's Health Initiative Observational Study. Analgesic use was reported at study baseline. Fifteen estrogens and estrogen metabolites and twelve androgens and androgen metabolites were quantified in baseline serum by liquid chromatography-tandem mass spectrometry. Linear regression with inverse probability weighting, stratified by menopausal hormone therapy (MHT) use, was used to estimate adjusted geometric mean concentrations of each hormone by analgesic use. Among women not currently using MHT (n=951), low-dose aspirin (<100 mg) use was associated with a higher serum concentration of estrone, estradiol, and 2,4, and 16 hydroxylated metabolites. Use of regular-dose aspirin ( {greater than or equal to} 100 mg), non-aspirin NSAIDs, and acetaminophen were not associated with serum concentrations of estrogens, androgens, or their metabolites. This study highlights the importance of examining aspirin use by dose and suggests that low-dose aspirin may influence endogenous estrogen concentrations.

Efficacy and utilization of an acceptance and commitment therapy-based smartphone application for smoking cessation among Black adults: secondary analysis of the iCanQuit randomized trial


2021 Diana Kwon; Margarita Santiago-Torres; Brianna Sullivan; Jonathan Bricker; Kristin Mull

BACKGROUND AND AIMS: Black adults who smoke are less likely to seek treatment and to succeed in quitting compared with other racial groups. The lack of efficacious and engaging trials for smoking cessation further contributes to this disparity. This study explored whether an acceptance and commitment therapy (ACT)-based smartphone application (iCanQuit) was more efficacious for smoking cessation than a United States Clinical Practice Guidelines (USCPG)-based smartphone application (QuitGuide) among Black adults. DESIGN: Secondary analysis of a two-arm randomized trial with 12-month follow-up. SETTING: United States (US). PARTICIPANTS: A total of 554 Black adults who smoke daily were recruited from 34 US states and enrolled between May 2017 and September 2018. INTERVENTIONS: Participants were randomized to receive iCanQuit (n=274) or QuitGuide (n=280) for 12 months. MEASUREMENTS: Smoking cessation outcomes were measured at 3, 6, and 12months. The primary outcome was self-reported complete-case 30-day point prevalence abstinence (PPA) at 12months. Secondary outcomes were 7-day PPA, missing-as-smoking imputation, multiple imputation, prolonged abstinence, and cessation of all tobacco products at 12months. Study retention, treatment engagement, and change in ACT-based processes were also compared between arms. FINDINGS: Study retention was 89% at 12months and did not differ by arm (P>0.05). The complete-case 30-day PPA was 28% for iCanQuit versus 20% for QuitGuide at 12 months (odds ratio [OR]=1.60; 95% confidence interval [CI] = 1.03, 2.46). Similar associations were observed for the missing-as-smoking imputation, although non-significant (25% iCanQuit vs 18% QuitGuide; OR=1.50; 95% CI = 0.98, 2.30). iCanQuit vs QuitGuide participants were significantly more engaged with iCanQuit application as measured by the number of logins from baseline to 6months (incidence rate ratio=3.26; 95% CI = 2.58, 4.13). Increased acceptance of cues to smoke mediated the effect of treatment on cessation (indirect effect: OR=0.20; 95% CI = 0.05, 0.29). CONCLUSIONS: Among Black adults, an acceptance and commitment therapy-based smartphone application appeared to be more efficacious and engaging for smoking cessation than the United States Clinical Practice Guidelines-based QuitGuide application.