Mary Mills’s research while affiliated with Georgetown University Medical Center and other places

Simple Summary Non-Hispanic Black breast cancer survivors have poorer outcomes than White survivors, but the biological mechanisms underlying these disparities are unclear. We discovered novel race-based differences in systemic DNA damage and repair activity among breast cancer survivors. This finding suggests DNA damage and repair are important basic science mechanisms in cancer disparities. Abstract Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.

Introduction The Achieving Cancer Equity through Identification, Testing, and Screening (ACE‐ITS) program is a community‐engaged framework to improve mammography maintenance and rates of genetic risk assessment, counseling, and testing using a multilevel approach that enhances patient navigation through mobile health and community education. Methods The ACE‐ITS program is based on the National Institute of Minority Health and Health Disparities research framework focused on the individual (genetic testing, screening navigation) and community (community‐based breast health education) levels and targeted to the biological‐ (genetic risk), behavioral‐ (mammography screening), sociocultural‐ (underserved Black and Hispanic women), and the health care system (patient navigation, automated text messages)–related domains. We further integrate the Practical Robust Implementation and Sustainability Model to describe our program implementation. Results In collaboration with genetic counselors and community partners, we created educational modules on mammography maintenance and genetic counseling/testing that have been incorporated into the navigator‐led community education sessions. We also implemented a universal genetic risk assessment tool and automated text message reminders for repeat mammograms into our mammography navigation workflow. Through the ACE‐ITS program implementation, we have collaboratively conducted 22 educational sessions and navigated 585 women to mammography screening over the 2020–2021 calendar years. From January to December 2021, we have also conducted genetic risk assessment on 292 women, of whom 7 have received genetic counseling/testing. Conclusions We describe a multilevel, community‐engaged quality improvement program designed to reduce screening‐related disparities in Black and Hispanic women in our catchment area.

Background: Self-reported data of physical activity are practical and inexpensive ways to collect data, although, subject to significant measurement errors. Most physical activity questionnaires used in the USA have been predominately validated among non-Hispanic White American populations with limited attention paid to the validity of the measures among racial/ethnic minorities. Additionally, there are limited studies that have evaluated factors related to over- and under-reporting errors linked to self-reported physical activity data, particularly among African Americans. The primary objectives of this study were to validate self-reported levels of physical activity and sedentary behavior among African-American men and women against objective measurements and to identify the factors related to under- and over-reporting. Methods: This study was a 7-day, cross-sectional study conducted on African-American men and women (n = 56) who were between 21-70 years of age. Participants were required to attend two study visits for the collection of self-reported and objective measurements of physical activity and sedentary behavior (VO2max, DEXA scan, anthropometrics, ActivPal accelerometer, resting metabolic rate (RMR) and International Physical Activity Questionnaire (IPAQ) questionnaire. Results: Overall, energy expenditure measured by ActivPal was 24.1 MET/hr/week whereas self-reported (IPAQ) energy expenditure was 52.66 MET/hr/week. Self-reported sedentary time was 40.37 h/week, whereas sedentary time measured by ActivPal was 63.03 h/week. Obese participants tended to over-report their physical activity levels more so than non-obese participants (Obese, Activpal-23.89 MET/hr/week vs IPAQ-58.98 MET/hr/week; Non-obese, Activpal - 24.48 MET/hr/week vs IPAQ - 42.55 MET/hr/week). Both obese and non-obese participants underestimated their sedentary time (Obese, Activpal - 66.89 h/week vs IPAQ-43.92 h/week; Non-obese, Activpal -56.07 h/week vs IPAQ - 33.98 h/week). Conclusions: The results of this study found that the ActivPal validated physical activity and sedentary behavior among African-Americans. Self-reported data were found to be highly variable, whereas the objective assessments of physical activity and sedentary behavior had limited variability. It was also found that obese individuals over-estimated their self-reported physical activity levels and under-estimated sedentary behavior in comparison to the ActivPal. These findings strongly support the need to measure physical activity and sedentary behaviors objectively, particularly among African-Americans.

Background: Cancer treatment related fatigue (CTRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. The primary objective of the PEDLAR study is to test the feasibility of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CTRF and improving health-related QOL among African-American breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in African-American women with breast cancer. Methods: It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Results: Participants in intervention group reported high satisfaction with exercise and adherence was >75% for exercise sessions. Conclusions: African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Fiber intake may be associated with lower risk of metabolic syndrome (MetS) but data from metabolically unhealthy African American women is sparse. We examined the association of dietary fiber intake and MetS among postmenopausal African American women with obesity. Baseline cross-sectional data from the Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial of 213 women (mean age 58.3 years) were used. Dietary intake was assessed by Food Frequency Questionnaires (FFQs). Multivariate linear and logistic regressions were performed to estimate associations of MetS with fiber intake and adherence to dietary fiber intake guidelines, respectively. Mean daily fiber intake was (10.33 g/1000kcal) in women with impaired metabolic health. We observed an inverse association of total fiber intake with MetS. One unit increase in energy-adjusted fiber intake was associated with a 0.10 unit decrease in the MetS z-score (p = 0.02). Similar results were obtained for both soluble and insoluble fiber. In multivariate-adjusted analyses, participants not adherent to fiber intake recommendations were more likely to have MetS as compared to those reporting intakes in the recommended range (adjusted odds ratio 4.24, 95% CI: 1.75, 10.30). Of the MetS components, high fasting glucose and high triglycerides were all associated with lower intake of fiber. Study participants who consumed a higher amount of fiber had a better overall metabolic profile and were less likely to have MetS in our cross-sectional analysis of postmenopausal African American women with obesity and unhealthy metabolic profiles.

Background Cancer related fatigue (CRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. Purpose The primary objective of the PEDLAR study is to test the efficacy of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CRF and improving health-related QOL among AA breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in AA women with breast cancer. Methods It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Results Participants in intervention group reported high satisfaction with exercise and adherence was > 75% for exercise sessions. Conclusions African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Obesity and low physical activity rates contribute to high rates of postmenopausal breast cancer in Black women. Use of new and exciting strategies to increase physical activity should be tested in health disparity populations at high risk of cancer. We tested the effect of a six-month exercise intervention using the active videogaming systems (exergaming) on anthropometric markers, body composition, and cardiovascular fitness (VO2max) in overweight and obese Black women. We conducted a six-month, two-arm randomized clinical trial comparing an exergaming intervention group to a control group in 100 cancer-free, overweight/obese, sedentary Black women who were 40-59 years of age. Participants were randomized to a supervised facility-based exergaming group (n=50) or a usual care control group (n=50). Participants in the exergaming group followed an exercise program using the Nintendo Wii Fit and/or the X-Box Kinect gaming systems under supervision of a clinical exercise physiologist. Control group participants were asked to maintain their normal daily activities. Endpoints were assessed at baseline, 3 months, and 6 months. Assessments included measurements of demographic variables, medical history, physical activity, VO2max, anthropometric variables (height, weight, waist and hip circumferences), and body composition. Distribution of baseline characteristics between exergaming and control groups was comparable except for education status and BMI. Data on 3 month and 6-month follow-up were available for 66 participants. Follow-up rates were similar for exergaming and control groups. Compared to control group participants whose waist circumference on average remained unchanged, exergaming group participants had lower waist circumference at 3-months and 6- months compared to baseline (mean change: -2.54 cm, P=0.05). Exergaming participants also had small changes in weight (-1.4 lbs) at 6 months compared to control group in whom average weight remained unchanged but this finding was not statistically significant. Fat mass and lean mass as measured by DXA did not show any changes at 3-months or 6-months in either the exergaming or the control group. This pilot study of a short-term exergaming in overweight/obese Black women was associated with small changes in waist circumference in the intervention group. Given the challenges associated with traditional physical activity interventions to reduce cancer risk, new and non-traditional interventions like exergaming should be tested in larger studies in health disparity populations. Citation Format: Chiranjeev Dash, Jennifer Hicks, Vivian Watkins, Mary Mills, James Hagberg, Lucile L. Adams-Campbell. An exergaming intervention to reduce breast cancer risk in Black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4219. doi:10.1158/1538-7445.AM2017-4219

Background: Fatigue is an important side-effect of radiation therapy (RT) for treatment of early stage breast cancer. Evidence on the efficacy of physical activity (PA) interventions in reducing fatigue among Black cancer patients undergoing RT is lacking. In a randomized controlled trial we tested the efficacy of a structured PA intervention, coinciding with the start of RT, in reducing cancer-related fatigue among Black patients undergoing RT for breast cancer. Methods: We randomly assigned 30 Black, sedentary, RT-naïve, non-pregnant patients diagnosed with stage 0-IIIA breast cancer who had completed adjuvant or neo-adjuvant chemotherapy and were scheduled for RT to the PA intervention (n = 15) and control groups (n = 15). PA intervention was an 8-week structured, moderate-intensity aerobic exercise regimen (75 minutes/week) using PEDLARS (portable stationary cycle ergometers) concurrent with RT. Fatigue was measured by using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) survey, a 13-item scale whose score ranges from 0 to 52 with a higher score denoting lower fatigue. We used ANCOVA to compare fatigue levels between the groups at T8 weeks after adjusting for baseline (T0) fatigue levels. We also compared change in fatigue scores (T8 weeks - T0) using 2-sample t-tests. All tests were double-sided with alpha = 0.05. Results: 27 women completed baseline and follow-up assessments. After adjusting for baseline fatigue scores, intervention group participants reported lower fatigue at T8 weeks than the control group (42.53 vs. 37.12; P = 0.17). Intervention group participants improved their fatigue scores at T8 weeks compared to T0 (mean change +1.3) but the control group did not (mean change -1.91; P = 0.42). Conclusion: Although statistically not significant, moderate-intensity exercise regimen among Black breast cancer patients undergoing RT was associated with lower RT-associated fatigue. This trial demonstrated the feasibility and acceptability of conducting a randomized clinical trial of a moderate-intensity exercise program among women initiating RT for breast cancer. Citation Format: Chiranjeev Dash, Mary Mills, Vivian Watkins, Pamela Randolph-Jackson, Claudine Isaacs, Kepher Makambi, Lucile L. Adams-Campbell. Moderate-intensity exercise to reduce radiation therapy-related fatigue in black breast cancer patients: A feasibility trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3467.

Background: Cancer related fatigue (CRF) is a common and debilitating side-effect of radiotherapy in breast cancer patients. Physical activity interventions can attenuate CRF but evidence in African-American women with breast cancer is lacking. Methods/design: The "Pedlar" Study is a prospective, 8-week structured moderate-intensity exercise intervention, delivered concurrently with radiotherapy, to reduce CRF and improve health-related quality of life among African American breast cancer patients. Forty African American women with breast cancer scheduled to receive radiation therapy at MedStar Washington Hospital Center will be randomized to one of the two trial arms: 1) a facility-based aerobic exercise utilizing a portable stationary pedal exerciser; and 2) a control group. Intervention arm participants will exercise at the hospital either before or after their radiation treatment. Assessments will be conducted at baseline, 4, and 8weeks. The outcome variables are CRF, biomarkers of inflammation, and health-related quality of life. Discussion: The Pedlar Study will provide preliminary evidence on whether a short-term moderate-intensity exercise intervention might be effective in reducing CRF in African American women undergoing radiotherapy for breast cancer, and whether this effect is mediated by inflammation.