br The ability to predict the subset of patients
The ability to predict the subset of patients with breast cancer who are at risk for chemotherapy-related frailty before starting treat-ment could help clinicians while making decisions about cancer treat-ments and assist in identifying a population of patients that might benefit from a targeted intervention. Given the fact that these inflam-matory biomarkers (IL-6, sTNFRI, and sTNFRII) are assayed from blood and can be easily incorporated into pre-treatment workup, suggests that they could be ideal biomarkers. While further validation studies are needed, there could ultimately be clinical utility for help-ing to predict which patients with breast cancer will develop chemotherapy-induced frailty. Multiple studies have demonstrated the relationships between frailty and treatment-related toxicities [8,42]. Yuan et al. recently demonstrated that pre-chemotherapy levels of IL-6 are associated with reduced relative dose intensity in patients with breast cancer . The levels of inflammatory markers
assessed in our study may thus guide treatment decision-making processes, including treatment options and the incorporation of be-havioral interventions with the goal of reducing the risk of functional decline post-chemotherapy, thereby reducing morbidity and improv-ing quality of life.
One of the limitations of the study was that we were not able to evaluate the effects of IL-6, TNFRI, and TNFRII on unintentional weight loss and its contribution to the frailty U-46619 due to the use of a modified Fried score. Future prospective studies are needed to confirm our results in a larger sample with the inclusion of unintentional weight loss. The associations between other factors such as race, past surgery, and pre-chemotherapy frailty with chemotherapy-induced frailty need to be further assessed. Additional studies are also needed to vali-date the cutoff levels of IL-6, TNFRI, and TNFRII that are predictive of frailty in patients with breast cancer. We will continue to evaluate the effect of elevated pre-chemotherapy levels of IL-6, TNFRI, and TNFRII on sustained post-chemotherapy frailty in a larger sample size with additional follow-ups to determine how this increased post-chemotherapy frailty affects treatment outcomes and quality of life over a longer time-scale. More work is necessary to elucidate the molecular mechanisms involved in the inflammatory pathways that contribute to frailty in patients with cancer about to undergo treatment. These analyses should be expanded to include not only patients with breast cancer but also patients with other solid malignancies. These re-sults will improve our understanding on how to appropriately manage patients with cancer who are at risk of developing frailty, ultimately im-proving their outcomes.
In summary, our study provides evidence that inflammatory markers may be used to predict frailty in a breast cancer population about to undergo treatment, and may serve as clinically useful biomarkers.
Authors' Disclosures of Potential Conflicts of Interest
The authors have no relevant conflicts of interest to report.
Conception and design: Nikesha Gilmore, Allison Magnuson, Supriya Mohile, Michelle Janelsins.
Provision of study materials or participants: Michelle Janelsins, Sharon Cole, Benjamin T. Esparaz, Jeffrey K. Giguere. Statistical analysis: Nikesha Gilmore, Lianlian Lei.
Data analysis and interpretation: Nikesha Gilmore, Sindhuja Kadambi, Lianlian Lei, Kah Poh Loh, Mostafa Mohamed, Allison Magnuson, Supriya Mohile, Michelle Janelsins. Manuscript preparation: Nikesha Gilmore, Sindhuja Kadambi, Lianlian Lei, Supriya Mohile, Michelle Janelsins.
Final approval of manuscript: Nikesha Gilmore, Sindhuja Kadambi, Lianlian Lei, Kah Poh Loh, Mostafa Mohamed, Allison Magnuson, Sharon Cole, Benjamin T. Esparaz, Jeffrey K. Giguere, Supriya Mohile, Michelle Janelsins.
We wish to acknowledge Drs. Susan Rosenthal and Amber Kleckner for their editorial assistance.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
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