The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters

Abstract

// Barbara Brouwers 1 , Sigrid Hatse 1 , Lissandra Dal Lago 2 , Patrick Neven 3 , Peter Vuylsteke 4 , Bruna Dalmasso 1,5 , Guy Debrock 6 , Heidi Van Den Bulck 7 , Ann Smeets 3 , Oliver Bechter 1 , Jithendra Kini Bailur 8 , Cindy Kenis 9 , Annouschka Laenen 10 , Patrick Schöffski 1 , Graham Pawelec 8,11 , Fabrice Journe 12 , Ghanem-Elias Ghanem 12 and Hans Wildiers 1,3 1 Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium 2 Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium 3 Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium 4 Department of Medical Oncology, Clinique et Maternité Sainte-Elisabeth, Namur, Belgium 5 Department of Internal Medicine, Istituto di Ricerca a Carattere Clinico e Scientifico (IRCCS), Azienda Ospedaliera Universitaria (AOU) San Martino Istituto Nazionale Tumori (IST), Genoa, Italy 6 Department of Medical Oncology, Ziekenhuizen Oost Limburg (ZOL), Genk, Belgium 7 Department of Medical Oncology, Imelda Ziekenhuis Bondheiden, Belgium 8 Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany 9 Department of General Medical Oncology and Geriatric Medicine, University Hospitals Leuven, Belgium 10 Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Leuven, Belgium 11 School of Science and Technology, Nottingham Trent University, Nottingham, UK 12 Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium Correspondence to: Barbara Brouwers, email: // Keywords : breast cancer, older patients, adjuvant chemotherapy, biological aging, aging biomarkers Received : February 16, 2016 Accepted : April 08, 2016 Published : April 18, 2016 Abstract Purpose: This prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on biological and clinical markers of aging and frailty. Methods: Women ≥ 70 years old with early breast cancer were enrolled after surgery and assigned to a chemotherapy (Docetaxel and Cyclophosphamide) group (CTG, n =57) or control group (CG, n =52) depending on their planned adjuvant treatment. Full geriatric assessment (GA) and Quality of Life (QoL) were evaluated at inclusion (T0), after 3 months (T1) and at 1 year (T2). Blood samples were collected to measure leukocyte telomere length (LTL), levels of interleukin-6 (IL-6) and other circulating markers potentially informative for aging and frailty: Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), Insulin-like Growth Factor 1 (IGF-1), Monocyte Chemotactic Protein 1 (MCP-1) and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES). Results: LTL decreased significantly but comparably in both groups, whereas IL-6 was unchanged at T2. However, IL-10, TNF-α, IGF-1 and MCP-1 suggested a minor biological aging effect of chemotherapy. Clinical frailty and QoL decreased at T1 in the CTG, but recovered at T2, while remaining stable in the CG. Conclusion: Chemotherapy (TC) is unlikely to amplify clinical aging or induce frailty at 1 year. Accordingly, there is no impact on the most established aging biomarkers (LTL, IL-6).