1819MO - Systemic inflammation, unhealthy behaviors, and cancer-related fatigue (CRF) among survivors of breast cancer (BC)

Background

Most biological underpinnings of CRF are elusive, however inflammatory activation was suggested as a potential mechanism. Behavioral interventions (e.g., exercise) can reduce CRF, including by modulating inflammation. We aimed to assess associations between pre-treatment (tx) inflammation and post-tx CRF, and between pre- to post-(tx) changes in inflammation and health behaviors among survivors of BC.

Methods

Patients (pts) with stage I-III HR+/HER2- BC were included from CANTO (NCT01993498). Serum inflammatory markers (IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IFNg, IL-1, IL1Ra, TNF-a, CRP) were assessed at BC diagnosis (pre-tx) and 2 years later (post-tx). Multivariable logistic regression assessed associations between pre-tx inflammation and post-tx CRF of clinical importance (EORTC QLQ-C30≥40). Behavioral determinants (Body Mass Index, physical activity [GPAQ-16], and smoking) were described by pre-tx levels of inflammatory markers and their post-tx change.

Results

Among 1208 pts, 34% reported post-tx CRF. High pre-tx IL-6 was associated with post-tx CRF (adjusted Odds Ratio v low [Q4 v 1] 2.06 [95%CI 1.40-3.03]). Pts with high pre-tx IL-6 (v low) were more likely to be overweight or obese (62% v 24%), physically inactive (54% v 37% reported <10 MET-h/week; median total activity: 8 [Q1-Q3 0-28] v 16 [4-46]; transport/leisure time activity: 4 [0-18] v 14 [2-28]), and current smokers (20% v 17%). From pre- to post-tx, 26% and 13% pts had a meaningful increase or decrease in IL-6, respectively. Increased IL-6 levels (v decreased) were associated with weight gain (mean weight change among pts that were obese at diagnosis [19%]: +0.7 Kg [95%CI +0.1 to +1.4] v -0.4 [-0.8 to -0.1]), and reduced physical activity (mean change in transport/leisure time activity: -3 MET-h/week [-7 to +1] v +1 [-2 to +3]).

Conclusions

High levels of pre-tx inflammatory markers (IL-6) were associated with post-tx CRF of clinical importance 2 years later. Unhealthy weight and reduced activity were determinants of high pre-tx inflammation and increased post-tx inflammation. Studies are warranted to assess whether early interception of modifiable unhealthy behavioral targets may prevent post-tx CRF by modulation of persistent inflammation.

Clinical trial identification

NCT01993498.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

This work was supported by Conquer Cancer, the American Society of Clinical Oncology (ASCO), and Rising Tide Foundation for Clinical Cancer Research [Career Pathway Grant in Symptom Management to ADM]; Foundation ARC [grant number ARCPGA2022010004401_4882 to ADM]; Breast Cancer Research Foundation [grant number not applicable] to IVL; Susan G. Komen [grant number Career Catalyst Research grant CCR17483507 to IVL]; Foundation Gustave Roussy [grant number not applicable to IVL]; and the French Government under the “Investment for the Future” program managed by the National Research Agency (ANR) [grant number ANR-10-COHO-0004 (CANTO); grant number ANR-18-IBHU-0002 (PRISM); grant number ANR-17-RHUS-008 (MyPROBE) to FA]. Funders had no role in collection, analysis or interpretation of data.

Disclosure

A. Di Meglio: Financial Interests, Personal, Advisory Board: Kephren, Medycis, Techspert. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: UNICANCER. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, Ipsen, Bayer, Astellas, Eisai, Seagen, Novocure, Pfizer; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Novartis/3A, Eisai, Amgen, Eisai; Financial Interests, Institutional, Invited Speaker: viatris; Financial Interests, Institutional, Coordinating PI: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, Astellas; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Member: GCIG; Other, Other, travel and congress: MSD, Ipsen, Chugai; Other, Other, travel: GSK, Eisai. P.H. Cottu: Financial Interests, Personal, Advisory Board: Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Pfizer, Lilly; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Lilly, Gilead; Financial Interests, Institutional, Funding: Novartis. O. Tredan: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis-Sandoz, Lilly, MSD, AstraZeneca, Pierre Fabre Oncologie, Seagen, Daiichi Sankyo, Gilead, Eisai, Stemline-Menarini, Veracyte, Exact Sciences. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. I.V. Vaz Luis: Financial Interests, Institutional, Invited Speaker: Amgen, Pfizer/Edimark, AstraZeneca; Financial Interests, Institutional, Writing Engagement: Pfizer/Edimark; Financial Interests, Institutional, Advisory Board, Consulting/ AB: Novartis; Financial Interests, Institutional, Advisory Board: Sandoz; Financial Interests, Personal, Other, Travelling: Novartis; Financial Interests, Institutional, Other, Research Funding: Resilience; Financial Interests, Institutional, Funding: Resilience; Non-Financial Interests, Member, Member of WG: ASCO. All other authors have declared no conflicts of interest.