Kyuwan Lee

Reducing the Risk of Breast Cancer Recurrence: an Evaluation of the Effects and Mechanisms of Diet and Exercise

With recent medical advances in diagnosis and treatment, the increasing numbers of long-term survivors of breast cancer is considerable and has resulted in the expansion of scientific research to include examination of lifestyle modifications as means of prevention of recurrence, new breast cancer events, and mortality. The objective of this report is to review randomized controlled trials (RCTs) including diet and/or exercise interventions on breast cancer recurrence in women with a history of breast cancer as well as pertinent recent epidemiologic evidence. Implicated biologic mechanisms are discussed to elucidate the impact of diet and exercise on disease recurrence.

Circuit aerobic and resistance exercise to target metabolic dysregulation in breast and prostate cancer survivors: The CARE trial study design.

TPS10126Background: Breast and prostate cancer survivors are at an increased risk of developing comorbidities such as metabolic syndrome (MSY), diabetes, and cardiovascular disease exacerbated by c...

Abstract 2627: A mathematical model to predict prognosis in breast cancer survivors following an exercise intervention

BACKGROUND Metabolic syndrome (MetS) and obesity are associated with increased risk of cardiovascular disease, type 2 diabetes, and cancer recurrence, and are higher in breast cancer survivors than age-matched postmenopausal women. We previously reported that exercise improves MetS and reduces pro-inflammatory biomarkers in obese breast cancer survivors. Whether these exercise-induced changes impact cancer outcomes is currently unknown. In this pilot study, we apply a robust mathematical analysis to identify biomarkers of MetS and obesity associated with clinical outcomes in obese breast cancer survivors following participation in a 16-week exercise intervention. EXPERIMENTAL DESIGN Eleven obese postmenopausal breast cancer survivors were randomized to either the exercise or control group. The exercise group participated in 16 weeks of supervised aerobic and resistance exercise sessions 3 times/week. Fasting blood and adipose tissue samples were analyzed for cytokine secretion, macrophage phenotype, and MetS. Prognostic outcomes included disease-free survival (DFS), overall survival (OS), distant DFS (DDFS), and recurrence-free interval (RFI). Partial least squares regression (PLSR) was used to quantify the importance of specific patient measurements in predicting the clinical response. PLSR is a multivariate regression analysis that quantifies the relationships between the participant characteristics and tissue and plasma measurements (inputs) and the clinical response (outputs) and can be used to identify which patient measurements most significantly associate with specific clinical outcomes. RESULTS MetS, macrophage phenotype, and inflammatory biomarkers were significantly improved in the exercise group compared to the control group (p CONCLUSIONS Exercise improves biomarkers related to MetS, obesity, and inflammation. The PLSR model quantifies patient characteristics and measurements associated with clinical outcomes. Our analysis provides quantitative insight into potential biomarkers to predict response to exercise and prompts the need for an in depth longitudinal study to determine the effects of exercise on long-term survival in obese breast cancer patients. Citation Format: Christina M. Dieli-Conwright, Jean-Hughes Parmentier, Steven D. Mittelman, Nathalie Sami, Kyuwan Lee, Stacey Finley. A mathematical model to predict prognosis in breast cancer survivors following an exercise intervention [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 2627.

Effects of high-intensity interval training on vascular function in breast cancer survivors undergoing anthracycline chemotherapy: design of a pilot study

Introduction Cardiovascular disease (CVD) mortality is higher among breast cancer survivors (BCS) who receive chemotherapy compared with those not receiving chemotherapy. Anthracycline chemotherapy is of particular concern due to anthracycline-related impairment of vascular endothelial cells and dysregulation of the extracellular matrix. One strategy proven to offset these impairments is a form of exercise known as high-intensity interval training (HIIT). HIIT improves endothelial function in non-cancer populations by decreasing oxidative stress, the main contributor to anthracycline-induced vascular dysfunction. The purpose of this pilot study is to assess the feasibility of an 8-week HIIT, as well as the HIIT effects on endothelial function and extracellular matrix remodelling, in BCS undergoing anthracycline chemotherapy. Methods and analysis Thirty BCS are randomised to either HIIT, an 8-week HIIT intervention occurring three times per week (seven alternating bouts of 90% of peak power output followed by 10% peak power output), or delayed group (DEL). Feasibility of HIIT is assessed by (1) the percentage of completed exercise sessions and (2) the number of minutes of exercise completed over the course of the study. Vascular function is assessed using brachial artery flow-mediated dilation and carotid intima media thickness. Extracellular matrix remodelling is assessed by the level of matrix metalloproteinases in the plasma. A repeated-measures analysis of covariance model will be performed with group (HIIT and DEL group) and time (pre/post assessment) as independent factors. We hypothesise that HIIT will be feasible in BCS undergoing anthracycline chemotherapy, and that HIIT will improve endothelial function and extracellular matrix remodelling, compared with the DEL group. Success of this study will provide evidence of feasibility and efficacy to support a larger definitive trial which will impact cancer survivorship by decreasing anthracycline-induced vascular dysfunction, thereby benefiting cardiovascular markers that are related to CVD risk. Ethics and dissemination This trial was approved by the University of Southern California Institutional Review Board (HS-15–00227). Trial registration number NCT02454777; Pre-results.

Abstract 985: Adipose tissue inflammation in breast cancer survivors: Effects of a 16-week aerobic and resistance exercise intervention

Background and Purpose: Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. There are over 2.5 million breast cancer survivors, 64% of whom are overweight/obese (BMI >25 kg/m2). A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs, and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter adipose tissue inflammation by changing ATM phenotype and cytokine secretion in obese postmenopausal breast cancer survivors. Experimental Design: Twenty obese postmenopausal breast cancer survivors were recruited from USC and randomized to either the exercise (EX) or control (CON) group. The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Sessions included total-body resistance training consisting of 8 exercises with a rest period of 45 seconds between each set of resistance exercise followed by 30 minutes of moderate-vigorous intensity (65-80% HRmax) aerobic exercise. The CON group was asked to maintain their current activity levels. Superficial subcutaneous abdominal adipose tissue biopsies were performed at baseline and following the 16-week study period. Adipose tissue samples were analyzed using fluorescence-activated cell sorting (FACS) to characterize ATM characterization (M1 vs M2). Portions (~100 mg) of each biopsy were incubated in media overnight to measure cytokine secretion. A 2x2 (group x time) repeated measures ANOVA was used to evaluate changes in adipose tissue and systemic inflammation. Summary of Results: At baseline, there were no group differences (p>0.05) in age (55.1±5.2 yrs), BMI (34.4±7.5 kg/m2), percent body fat (36.2±4.9%), or ATM M1 (25.4±6.7%) and M2 (4.2±0.9%) levels. EX was associated with a significant decrease in ATM M1 (-18.8±7.3%) and increase in ATM M2 (9.6±1.6%; p 0.01). Conclusions: A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized controlled trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence. Citation Format: Christina M. Dieli-Conwright, Jean Hughes-Parmentier, Kyuwan Lee, Darcy Spicer, Wendy Mack, Fred Sattler, Steven D. Mittelman. Adipose tissue inflammation in breast cancer survivors: Effects of a 16-week aerobic and resistance exercise intervention [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 985. doi:10.1158/1538-7445.AM2017-985

PS 17-28 THE EFFECT OF A COMBINED AEROBIC AND RESISTANCE EXERCISE TRAINING ON BLOOD PRESSURE IN BREAST CANCER SURVIVORS WITH HYPERTENSION: A RANDOMIZED CONTROLLED TRIAL

Objective: Despite improvements in survival rate, breast cancer survivors (BCS) are at elevated risk for hypertension (HTN) and its consequences, possibly due to pre-existing obesity and breast cancer therapies. HTN is a major risk factor for stroke, coronary heart disease, and congestive heart failure. Thus, the purpose of this study was to examine the effects of a 16-week aerobic and resistance exercise intervention on blood pressure (BP) in BCS with HTN. Design and method: Twenty-six BCS (Stage I-III) with HTN who completed therapy for early stage breast cancer within 6 months prior to study enrollment were randomized to the Control (CON; n = 13) or the Exercise (EX; n = 13) group. The EX group underwent supervised aerobic and resistance exercise sessions 3 times a week for 16 weeks. The CON group was asked to maintain their current level of activity. Resting systolic and diastolic BP were assessed before and after the 16-week study period. Paired t-test and two-way repeated measures ANOVA were used to examine the effects of exercise training on BP. Results: The EX and CON did not differ by age (52.5 ± 8.2yr), body mass index (29.6 ± 5.4kg/m2), waist circumference (101.3 ± 14.5cm), systolic BP (135.9 ± 8.2 mmHg) and diastolic BP (89.9 ± 4.6). Following 16 weeks, systolic and diastolic BP were significantly reduced (6% and 11%, respectively) in the EX group (P = 0.01). The CON group had no significant change on systolic and diastolic BP (P > 0.05). There was a significant time (pre vs. post) by group (EX and CON) interaction for systolic and diastolic BP (P = 0.04 and 0.01, respectively) in BCS with HTN. Conclusions: A 16-week combined exercise training intervention under supervised training conditions is an effective approach to reduce BP in BCS with HTN, implying that exercise is important during cancer survivorship to reduce the risk for cardiovascular disease mortality.