Research Paper|Volume 16, Issue 18|pp 12432—12442

Frailty and pre-frailty associated with long-term diminished physical performance and quality of life in breast cancer and hematopoietic cell transplant survivors

Najla El Jurdi^1,², Hok Sreng Te², Qing Cao³, Char Napurski², Shuo Wang⁴, Andre Robinson^2,³, Mukta Arora⁵, Heba ElHusseini², Fiona He², Laura J. Niedernhofer⁶, Bharat Thyagarajan⁴, Anna Prizment⁴, Shernan Holtan², Anne Hudson Blaes², Matthew J. Yousefzadeh^6,⁷

¹Blood and Marrow Transplant Program, Departments of Medicine and Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA
²Division of Hematology, Oncology, And Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55454, USA
³Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55454, USA
⁴Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55454, USA
⁵Amgen, Thousand Oaks, CA 91320, USA
⁶Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55454, USA
⁷Columbia Center for Translational Immunology and Columbia Center for Healthy Longevity, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA

* Co-senior author

Received: February 27, 2024Accepted: July 18, 2024Published: September 26, 2024

https://doi.org/10.18632/aging.206109

Copyright: © 2024 Jurdi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Physical frailty as a sign of accelerated aging is not well characterized in breast cancer (BC) and hematopoietic cell transplant (HCT) survivors and its correlation with outcomes and quality of life (QOL) is not defined. We conducted a prospective study to determine the prevalence of frailty in adult BC and HCT survivors, examine its impact on QOL, and determine its association with p16^INK4a, a molecular biomarker for biological aging. The study included 59 BC and 65 HCT survivors. Median age was 60 years (range 27-81), 68.5% were female and 49.2% were 18-59 vs. 51.8% ≥60 years old. A total of 71 (57.3%) were “fit” (frailty score 0) vs. 53 (42.7%) were pre-frailty/frail (frailty scores ≥1), and of the latter 17 (32.1%) were BC and 36 (67.9%) HCT patients. On multivariate analysis, patients >60 years were twice as likely to be frail (OR 2.04, 95% CI, 0.96-4.33; p=0.07), HCT were more likely to be frail compared to BC patients, and female HCT had 2.43 (95% CI, 0.92-6.40) and male HCT patients had 3.25 (95% CI, 1.37-7.72) times higher risk of frail; p=0.02. Frailty was associated with significant decline in QOL, measured by Medical Outcomes Study (MOS) Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), and FACT (Functional Assessment of Cancer Therapy) scores. p16^INK4a expression was higher in those who were frail, older than 60, and with higher expression in frail vs. fit patients who are 18-59 years. Our study highlights the high prevalence of frailty in survivors with detrimental effects on physical and overall wellbeing, and supports an association between frailty and the senescence marker p16^INK4a.