Nutrients 2021, 13, 4091. https://doi.org/10.3390/nu13114091 www.mdpi.com/journal/nutrients Article Effect of a Remotely Delivered Weight Loss Intervention in Early-Stage Breast Cancer: Randomized Controlled Trial Marina M. Reeves 1, *, Caroline O. Terranova 1 , Elisabeth A. H. Winkler 1 , Nicole McCarthy 2 , Ingrid J. Hickman 3 , Robert S. Ware 4 , Sheleigh P. Lawler 1 , Elizabeth G. Eakin 1 and Wendy Demark-Wahnefried 5 1 School of Public Health, The University of Queensland, Brisbane 4006, Australia; caroline.terranova@qut.edu.au (C.O.T.); e.winkler@sph.uq.edu.au (E.A.W.); s.lawler@sph.uq.edu.au (S.P.L.); e.eakin@uq.edu.au (E.G.E.) 2 Wesley Centre, Icon Cancer Care, Brisbane 4066, Australia; Nicole.McCarthy@icon.team 3 Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane 4102, Australia; i.hickman@uq.edu.au 4 Menzies Health Institute Queensland, Griffith University, Brisbane 4111, Australia; r.ware@griffith.edu.au 5 O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA; demark@uab.edu * Correspondence: marina.reeves@uq.edu.au, +617 3346 4692 Abstract: Limited evidence exists on the effects of weight loss on chronic disease risk and patient- reported outcomes in breast cancer survivors. Breast cancer survivors (stage I-III; body mass index 25–45 kg/m 2 ) were randomized to a 12-month, remotely delivered (22 telephone calls, mailed mate- rial, optional text messages) weight loss (diet and physical activity) intervention (n = 79) or usual care (n = 80). Weight loss (primary outcome), body composition, metabolic syndrome risk score and components, quality of life, fatigue, musculoskeletal pain, menopausal symptoms, fear of recur- rence, and body image were assessed at baseline, 6 months, 12 months (primary endpoint), and 18 months. Participants were 55 ± 9 years and 10.7 ± 5.0 months post-diagnosis; retention was 81.8% (12 months) and 80.5% (18 months). At 12-months, intervention participants had significantly greater improvements in weight (−4.5% [95%CI: −6.5,−2.5]; p < 0.001), fat mass (−3.3 kg [−4.8,−1.9]; p < 0.001), metabolic syndrome risk score (−0.19 [−0.32,−0.05]; p = 0.006), waist circumference (−3.2 cm [−5.5,−0.9]; p = 0.007), fasting plasma glucose (−0.23 mmol/L [−0.44,−0.02]; p = 0.032), physical quality of life (2.7 [0.7,4.6]; p = 0.007; Cohen’s effect size (d) = 0.40), musculoskeletal pain (−0.5 [−0.8,−0.2]; p = 0.003; d = 0.49), and body image (−0.2 [−0.4,−0.0]; p = 0.030; d = 0.31) than usual care. At 18 months, effects on weight, adiposity, and metabolic syndrome risk scores were sustained; however, signifi- cant reductions in lean mass were observed (−1.1 kg [−1.7,−0.4]; p < 0.001). This intervention led to sustained improvements in adiposity and metabolic syndrome risk. Keywords: obesity; exercise; nutrition; supportive care; survivorship; telehealth 1. Introduction Attention has been focused on modifiable risk factors (diet, obesity, physical activity) as a means to improve breast cancer outcomes [1,2]. Physical activity has been associated with reduced breast cancer recurrence risk and increased survival [3,4], with exercise in- terventions producing improvements in quality of life, physical function, and fatigue [5– 7]. Breast cancer survivors who maintain a healthful weight (body mass index (BMI) = 18.5–24.9 kg/m 2 ) have 30–40% reduced mortality risk compared to those with obesity (BMI ≥ 30 kg/m 2 ) [8]. Consequently, weight management, physical activity, and dietary changes are encouraged for breast cancer survivors [1,2,9,10]. Weight loss trials in early-stage breast cancer have shown that modest weight loss is safe and feasible [11,12], with ongoing trials assessing effects on survival [13–15]. With Citation: Reeves, M.M.; Terranova, C.O.; Winkler, E.A.H.; McCarthy, N.; Hickman, I.J.; Ware, R.S.; Lawler, S.P.; Eakin, E.G.; Demark-Wahnefried, W. Effect of a Remotely Delivered Weight Loss Intervention in Early-Stage Breast Cancer: Randomized Controlled Trial. Nutrients 2021, 13, 4091. https://doi.org/10.3390/nu13114091 Academic Editor: Vicente Martinez Vizcaino Received: 19 October 2021 Accepted: 12 November 2021 Published: 15 November 2021 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2021 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (http://crea- tivecommons.org/licenses/by/4.0/).