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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.

Aboalela N, Lyon D, Elswick RK, Kelly DL, Brumelle J, Bear HD, Jackson-Cook C - PLoS ONE (2015)

Bottom Line: An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Changes in MN/cytome abnormality frequencies associated with radiotherapy.At the baseline and 4 weeks (mid-chemo) time points, no significant differences in the chromosomal instability frequencies were observed between the women who did (white circles) or did not (black circles) receive radiation therapy. However, a statistically significantly increase in MN/cytome abnormality frequencies was observed at six months (compared to baseline) for the group of women receiving radiotherapy versus the group not receiving radiation (see Table 6). Also, for the subset of women who received radiotherapy, this increase in chromosomal instability values persisted at the 1 year time point (p<0.0001).
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pone.0133380.g003: Changes in MN/cytome abnormality frequencies associated with radiotherapy.At the baseline and 4 weeks (mid-chemo) time points, no significant differences in the chromosomal instability frequencies were observed between the women who did (white circles) or did not (black circles) receive radiation therapy. However, a statistically significantly increase in MN/cytome abnormality frequencies was observed at six months (compared to baseline) for the group of women receiving radiotherapy versus the group not receiving radiation (see Table 6). Also, for the subset of women who received radiotherapy, this increase in chromosomal instability values persisted at the 1 year time point (p<0.0001).

Mentions: The final model is reported in Table 6 and showed significant effects attributable to a subset of items in the base model, as well as effects for race (p = 0.0061), luminal B tumors (p = 0.0053) and PSS (p = 0.0129). When assessing the effect of chemotherapies on somatic chromosomal instability levels, at the mid-chemo time point (scheduled prior to the fourth treatment [visit 2]) the women who received TAC chemotherapy showed the greatest increase in MN/cytome abnormality frequencies when compared to baseline values (p = 0.0329) (Fig 2). Also, the mean MN/cytome abnormality frequency was noted to be significantly lower at baseline than at visit 4 for the women who received TAC (p<0.001) or TC (p = 0.014) regimens, but not the TCH treatment (p = 0.0884). An impact of radiotherapy on MN/cytome abnormality frequencies was demonstrated by a significant increase in chromosomal instability levels one year post the initiation of chemo [visit 4] compared to baseline [visit 1] in the women receiving radiotherapy (p<0.0001)(Fig 3). Overall, a significant change in chromosomal instability frequencies was observed over time, with this change differing based on whether the women received radiotherapy (Radiation by Visit; p = 0.0052)(Table 6).


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.

Aboalela N, Lyon D, Elswick RK, Kelly DL, Brumelle J, Bear HD, Jackson-Cook C - PLoS ONE (2015)

Changes in MN/cytome abnormality frequencies associated with radiotherapy.At the baseline and 4 weeks (mid-chemo) time points, no significant differences in the chromosomal instability frequencies were observed between the women who did (white circles) or did not (black circles) receive radiation therapy. However, a statistically significantly increase in MN/cytome abnormality frequencies was observed at six months (compared to baseline) for the group of women receiving radiotherapy versus the group not receiving radiation (see Table 6). Also, for the subset of women who received radiotherapy, this increase in chromosomal instability values persisted at the 1 year time point (p<0.0001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4503400&req=5

pone.0133380.g003: Changes in MN/cytome abnormality frequencies associated with radiotherapy.At the baseline and 4 weeks (mid-chemo) time points, no significant differences in the chromosomal instability frequencies were observed between the women who did (white circles) or did not (black circles) receive radiation therapy. However, a statistically significantly increase in MN/cytome abnormality frequencies was observed at six months (compared to baseline) for the group of women receiving radiotherapy versus the group not receiving radiation (see Table 6). Also, for the subset of women who received radiotherapy, this increase in chromosomal instability values persisted at the 1 year time point (p<0.0001).
Mentions: The final model is reported in Table 6 and showed significant effects attributable to a subset of items in the base model, as well as effects for race (p = 0.0061), luminal B tumors (p = 0.0053) and PSS (p = 0.0129). When assessing the effect of chemotherapies on somatic chromosomal instability levels, at the mid-chemo time point (scheduled prior to the fourth treatment [visit 2]) the women who received TAC chemotherapy showed the greatest increase in MN/cytome abnormality frequencies when compared to baseline values (p = 0.0329) (Fig 2). Also, the mean MN/cytome abnormality frequency was noted to be significantly lower at baseline than at visit 4 for the women who received TAC (p<0.001) or TC (p = 0.014) regimens, but not the TCH treatment (p = 0.0884). An impact of radiotherapy on MN/cytome abnormality frequencies was demonstrated by a significant increase in chromosomal instability levels one year post the initiation of chemo [visit 4] compared to baseline [visit 1] in the women receiving radiotherapy (p<0.0001)(Fig 3). Overall, a significant change in chromosomal instability frequencies was observed over time, with this change differing based on whether the women received radiotherapy (Radiation by Visit; p = 0.0052)(Table 6).

Bottom Line: An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus