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


CONCLUSIONS
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).
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Barbara
B
Brouwers
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Sigrid
S
Hatse
Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Lissandra
L
Dal Lago
Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium.
Patrick
P
Neven
Department of Medical Oncology, Clinique et Maternité Sainte-Elisabeth, Namur, Belgium.
Peter
P
Vuylsteke
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.|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.
Bruna
B
Dalmasso
Department of Medical Oncology, Ziekenhuizen Oost Limburg (ZOL), Genk, Belgium.
Guy
G
Debrock
Department of Medical Oncology, Imelda Ziekenhuis Bondheiden, Belgium.
Heidi
H
Van Den Bulck
Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium.
Ann
A
Smeets
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Oliver
O
Bechter
Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
Jithendra Kini
JK
Bailur
Department of General Medical Oncology and Geriatric Medicine, University Hospitals Leuven, Belgium.
Cindy
C
Kenis
Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Leuven, Belgium.
Annouschka
A
Laenen
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Patrick
P
Schöffski
Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.|School of Science and Technology, Nottingham Trent University, Nottingham, UK.
Graham
G
Pawelec
Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Fabrice
F
Journe
Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Ghanem-Elias
GE
Ghanem
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.|Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium.
Hans
H
Wildiers
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D005260:Female; D016330:Frail Elderly; D000073496:Frailty / Q000209:etiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects; D011446:Prospective Studies; D011788:Quality of Life; D016615:Telomere / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000970:Antineoplastic Agents; D015415:Biomarkers; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C583557:IGF1 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I
Gerotarget; adjuvant chemotherapy; aging biomarkers; biological aging; breast cancer; older patients