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Research article
Nikesha Gilmore
University of Rochester Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5079-1723
Michelle Janelsins
University of Rochester Medical Center
Corresponding Author
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Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.
Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n=581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time-points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time-points. Separate linear regressions were used to evaluate the associations of: 1) cell counts at T1 with frailty at T1, T2, and T3 and 2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time-point.
Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p<0.01) and returned to T1 levels by the T3 time-point (1.3 vs 1.3; p=0.85). At the T1 time-point, there was a positive association between cellular markers of inflammation and frailty: WBC (β=0.04; p<0.05), neutrophils (β=0.04; p<0.05), and NLR (β=0.04; p<0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β=0.02; p<0.05 and neutrophils: β=0.03; p<0.05, NLR: β=0.03; p<0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy.
Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy.
Trial Registration: ClinicalTrials.gov Identifier: NCT01382082
Keywords
frailty, chemotherapy, inflammation, breast cancer, immune cell profiles, cellular markers of inflammation
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
- CLEANFrailtyCellCountSupplementary20201206.docx
Supplementary Tables 1-6
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CURRENT STATUS: Published
View the published article at Breast Cancer Research.
Version 2
Posted 18 Dec, 2020
No community comments so far
Editorial decision: Accept
On 04 Jan, 2021
Review #1 received
Received 30 Dec, 2020
Reviewer #1 agreed
On 28 Dec, 2020
Reviewers invited
Invitations sent on 19 Dec, 2020
Editor assigned
On 06 Dec, 2020
Submission checks complete
On 06 Dec, 2020
Editor invited
On 06 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 09 Oct, 2020
Review #1 received
Received 26 Jul, 2020
Reviewers invited
Invitations sent on 20 Jul, 2020
Reviewer #1 agreed
On 20 Jul, 2020
Editor assigned
On 01 Jul, 2020
Submission checks complete
On 30 Jun, 2020
Editor invited
On 30 Jun, 2020
First submitted
On 29 Jun, 2020
Metrics
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HTML Views: ...
Subject Areas
Cancer Biology
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See the published version of this preprint at Breast Cancer Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Nikesha Gilmore
University of Rochester Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5079-1723
Michelle Janelsins
University of Rochester Medical Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Breast Cancer Research.
Version 2
Posted 18 Dec, 2020
No community comments so far
Editorial decision: Accept
On 04 Jan, 2021
Review #1 received
Received 30 Dec, 2020
Reviewer #1 agreed
On 28 Dec, 2020
Reviewers invited
Invitations sent on 19 Dec, 2020
Editor assigned
On 06 Dec, 2020
Submission checks complete
On 06 Dec, 2020
Editor invited
On 06 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 09 Oct, 2020
Review #1 received
Received 26 Jul, 2020
Reviewers invited
Invitations sent on 20 Jul, 2020
Reviewer #1 agreed
On 20 Jul, 2020
Editor assigned
On 01 Jul, 2020
Submission checks complete
On 30 Jun, 2020
Editor invited
On 30 Jun, 2020
First submitted
On 29 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Breast Cancer Research.
Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.
Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n=581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time-points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time-points. Separate linear regressions were used to evaluate the associations of: 1) cell counts at T1 with frailty at T1, T2, and T3 and 2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time-point.
Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p<0.01) and returned to T1 levels by the T3 time-point (1.3 vs 1.3; p=0.85). At the T1 time-point, there was a positive association between cellular markers of inflammation and frailty: WBC (β=0.04; p<0.05), neutrophils (β=0.04; p<0.05), and NLR (β=0.04; p<0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β=0.02; p<0.05 and neutrophils: β=0.03; p<0.05, NLR: β=0.03; p<0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy.
Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy.
Trial Registration: ClinicalTrials.gov Identifier: NCT01382082
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
- CLEANFrailtyCellCountSupplementary20201206.docx
Supplementary Tables 1-6
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