title: 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.
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.
authors.affiliation: Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Noran
authors.initials: N
authors.lastname: Aboalela
authors.affiliation: Family and Community Health Nursing, School of Nursing, Virginia Commonwealth University, Richmond, Virginia, United States of America; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Debra
authors.initials: D
authors.lastname: Lyon
authors.affiliation: Family and Community Health Nursing, School of Nursing, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: R K
authors.initials: RK
authors.lastname: Elswick
authors.affiliation: Family and Community Health Nursing, School of Nursing, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Debra Lynch
authors.initials: DL
authors.lastname: Kelly
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Jenni
authors.initials: J
authors.lastname: Brumelle
authors.affiliation: Division of Surgical Oncology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.affiliation: Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Colleen
authors.initials: C
authors.lastname: Jackson-Cook
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology* / Q000532:radiotherapy; D016923:Cell Death; D043171:Chromosomal Instability / Q000235:genetics*; D003710:Demography; D005260:Female; D005500:Follow-Up Studies; D006262:Health; D006801:Humans; D008019:Life Style; D016014:Linear Models; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000473:pathology; D048631:Micronucleus, Germline; D008875:Middle Aged; D008954:Models, Biological; D013315:Stress, Psychological / Q000209:etiology* / Q000235:genetics*; D055815:Young Adult