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Published in: Breast Cancer Research 1/2020

01-12-2020 | Fluorescence in Situ Hybridization | Research article

Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study

Authors: Areej A. Alhareeri, Kellie J. Archer, Han Fu, Debra E. Lyon, R. K. Elswick Jr, Debra L. Kelly, Angela R. Starkweather, Lynne W. Elmore, Yahya A. Bokhari, Colleen K. Jackson-Cook

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction.

Methods

To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23–71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy.
Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay].

Results

Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014–0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores).

Conclusions

We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman’s treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment.
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Metadata
Title
Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study
Authors
Areej A. Alhareeri
Kellie J. Archer
Han Fu
Debra E. Lyon
R. K. Elswick Jr
Debra L. Kelly
Angela R. Starkweather
Lynne W. Elmore
Yahya A. Bokhari
Colleen K. Jackson-Cook
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01368-6

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