Perceived Stress Levels, Chemotherapy, Radiation Treatment and Tumor Characteristics Are Associated with a Persistent Increased Frequency of Somatic Chromosomal Instability in Women Diagnosed with Breast Cancer: A One Year Longitudinal Study.

Noran Aboalela,Colleen Jackson-Cook,Harry D Bear,Debra Lynch Kelly,Debra Lyon,Jenni Brumelle,R K Elswick

doi:10.1371/journal.pone.0133380

Noran Aboalela, Colleen Jackson-Cook + Show 5 more

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https://doi.org/10.1371/journal.pone.0133380

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Journal: PloS one	Publication Date: Jul 15, 2015
Citations: 85	License type: CC BY 4.0

Affiliation: Virginia Commonwealth University

Abstract

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage breast cancer and quantified their somatic chromosomal instability levels using a cytokinesis-blocked micronuclear/cytome assay at 4 timepoints: before chemotherapy (baseline); four weeks after chemotherapy initiation; six months after chemotherapy (at which time some women received radiotherapy); and one year following chemotherapy initiation. Overall, a significant change in instability frequencies was observed over time, with this change differing based on whether the women received radiotherapy (p=0.0052). Also, significantly higher instability values were observed one year after treatment initiation compared to baseline for the women who received: sequential taxotere/doxorubicin/cyclophosphamide (p<0.001) or taxotere/cyclophosphamide (p=0.014). Significant predictive associations for acquired micronuclear/cytome abnormality frequencies were also observed for race (p=0.0052), tumor type [luminal B tumors] (p=0.0053), and perceived stress levels (p=0.0129). The impact of perceived stress on micronuclear/cytome frequencies was detected across all visits, with the highest levels of stress being reported at baseline (p =0.0024). These findings suggest that the cancer-related exposome has an impact on both healthy somatic cells and tumor cells, and may lead to persistent chromosomal instability. In addition, stress was a significant predictor of chromosomal instability; thus, interventions that aim to reduce stress may reduce acquired soma-wide chromosomal instability for cancer survivors.

Highlights

IntroductionInnovations in treatment approaches for women with early-stage breast cancer, such as the use of taxanes and anthracylines in sequential, standard or dose dense regimens (along with radiotherapy and/or hormonal antagonists), have resulted in improvements in survival rates [1,2]
Innovations in treatment approaches for women with early-stage breast cancer, such as the use of taxanes and anthracylines in sequential, standard or dose dense regimens, have resulted in improvements in survival rates [1,2]
A total of 77 women were recruited for this study, with only 3 women failing to complete the multiple visits required for this longitudinal investigation, which resulted in a 96% retention rate

Summary

Introduction

Innovations in treatment approaches for women with early-stage breast cancer, such as the use of taxanes and anthracylines in sequential, standard or dose dense regimens (along with radiotherapy and/or hormonal antagonists), have resulted in improvements in survival rates [1,2] These improvements in survival rates have been accompanied by reports from many survivors of the acquisition and persistence of adverse side effects, which include (but are not limited to): anxiety [3], depression [3], fatigue [4], cognitive dysfunction [5], sleep disturbance [6], and pain [7,8], which we categorize as “psychoneurological symptoms” (PNS). It is not known if these acquired PNS are associated with the treatments, the perceived stress that accompanies a diagnosis of cancer and its treatment, the cancer itself, or a combination of exposures to biological and psychological factors

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