Biologic profile to predict overall survival in non-metastatic breast cancer: A latent class analysis on aging biomarkers.

Authors

null

Claire Falandry

Unité d'Oncogériatrie, Centre Hospitalier Lyon Sud and CarMeN laboratory of Lyon University, Pierre-Benite, France

Claire Falandry , Barbara Anna Henk Brouwers , Cindy Kenis , Ann Smeets , Patrick Neven , Charlotte Cuerq , Karim Chikh , Sigrid Hatse , Hans Wildiers

Organizations

Unité d'Oncogériatrie, Centre Hospitalier Lyon Sud and CarMeN laboratory of Lyon University, Pierre-Benite, France, Department of Oncology, AZ Sint-Jan, Brugge, Belgium, Department of General Medical Oncology Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium, Department of Surgical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium, Multidisciplinary Breast Center, University Hospitals Leuven – Campus Gasthuisberg, Leuven, Belgium, Hospices Civils de Lyon, Université Lyon 1, Pierre-Bénite, France, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Pierre Bénite, France, Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium, Department of General Medical Oncology, University Hospitals Leuven & Department of Oncology, KU Leuven – University of Leuven, Leuven, Belgium

Research Funding

Institutional Funding
Fund for Scientific Research Flanders (FWO Vlaanderen) (Hans Wildiers), La Ligue nationale Contre le Cancer (Claire Falandry)

Background: The aging process is heterogeneous and the result of different biological mechanisms. Blood biomarkers involved in the aging process, aside from comprehensive geriatric assessment, may help clinicians when facing equivocal therapeutic decisions, for example adjuvant treatment at high risk of toxicities. Methods: This study was conducted on a previously published cohort (PMID 25989735) including 162 patients aged ≥70 years (“Old”) and 82 patients aged ≤60 years (“Young”) with newly diagnosed non-metastatic breast cancer. Serum samples collected from all patients at breast cancer diagnosis, before any treatment were available from the extensive Leuven blood biobank. Overall survival was evaluated with October 7, 2022 as data cutoff. A panel of blood aging biomarkers attributed to inflammation: IL6, MCP1, RANTES, telomere shortening: telomeric DNA ratio T/S, telomeric dysfunction: CRAMP, chitinase activity, and anabolism : IGF1. Considering a high risk of collinearity, we performed a latent class analysis (LCA) on the whole cohort, to delineate the respective roles of inflammaging, replicative senescence and sarcopenia on patient clusters. Results: In univariate analysis were significantly associated with a poorer survival: high MCP1, hazard ratio (HR) = 1.57 (95%CI 1.32-1.87), high chitinase activity, HR = 1.33 (95%CI 1.12-1.57), and low IGF1, HR = 1.76 (95%CI 1.47-2.11). The biomarkers correlation matrix identified a significant correlation of Chitinase activity with MCP1, IGF1, CRAMP; of CRAMP with IL6; and IGF1 with T/S ratio. LCA identified 2 biologic profiles within the population, representing 137 (56.1%, class 1) and 107 (43,9%, class 2) patients. Class 1 was associated with a significantly poorer overall survival: HR = 3.52 (95%CI 2.28-5.45), and age-adjusted HR = 1.77 (95%CI 1.12-2.80). The best predictors for class 1 membership were low IGF1 (89%), high MCP1 (82%), high chitinase activity (79%), high IL6 (69%). Class 1 represented 77% of the “Old” and 15% of the “Young” populations. Conclusions: Our results delineate an unfavorable biologic profile that transcends chronological age and significantly predicts a poorer overall survival, underpinned by markers of both inflammaging, telomeric dysfunction and sarcopenia. The strong correlation between markers argues for a unique underlying biological pathway. Noteworthy, high IGF1, usually considered as a risk factor for breast cancer progression, was associated with a better prognosis. Low IGF1, high chitinase activity and high MCP1 appear as promising predictive biomarkers.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Symptoms and Survivorship

Track

Symptom Science and Palliative Care

Sub Track

Geriatric Models of Care

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 12037)

DOI

10.1200/JCO.2023.41.16_suppl.12037

Abstract #

12037

Poster Bd #

405

Abstract Disclosures

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