Physical health-related quality of life trajectories over two years following breast cancer diagnosis in older women: a secondary analysis.

PURPOSE: To identify distinct trajectories of physical health-related quality of life (HRQoL) in older women over the first two years following breast cancer diagnosis, and to examine characteristics associated with trajectory group membership. METHODS: A secondary analysis of a longitudinal study of women diagnosed with stage I-III breast cancer who completed surveys within eight months of diagnosis and six, twelve, and eighteen months later that focuses on a subset of women aged ≥ 65 years (N = 145).Physical HRQoL was assessed using the Physical Component Score (PCS) of the SF-36 Health Survey. Finite mixture modeling identified distinct PCS trajectories. Multivariable logistic regression identified variables predictive of low PCS group membership. RESULTS: Two distinct patterns of PCS trajectories were identified. The majority (58%) of women had PCS above the age-based SF-36 population norms and improved slightly over time. However, 42% of women had low PCS that remained low over time. In multivariable analyses, older age, difficulty paying for basics, greater number of medical comorbidities, and higher body mass index were associated with low PCS group membership. Cancer treatment and psychosocial variables were not significantly associated. CONCLUSION: A large subgroup of older women reported very low PCS that did not improve over time. Older age, obesity, multiple comorbidities, and lower socioeconomic status may be risk factors for poorer PCS in women with breast cancer. Incorporating routine comprehensive geriatric assessments that screen for these factors may help providers identify older women at risk for poorer physical HRQoL post breast cancer treatment.

Factors associated with insomnia symptoms over three years among premenopausal women with breast cancer.

PURPOSE: We examined longitudinal trends and factors associated with insomnia over 3 years in a cohort of young breast cancer patients. METHODS: Women with stage I-III breast cancer at ≤ 45 years were recruited at five institutions from New York, Texas, and North Carolina, within 8 months of diagnosis (n = 836). Participants completed questionnaires every 6 months for 3 years. Linear mixed-effects models were used to examine insomnia over time, using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). We evaluated the relations of insomnia with demographic (age, race, education, income, employment, marital status), clinical (cancer stage, histologic grade, chemotherapy, radiation, hormone therapy, surgery, tumor size, body mass index, hot flashes), and social/behavioral variables (smoking status, social support, physical activity, depressive symptoms). RESULTS: At baseline, 57% of participants met or exceeded the cut-off for clinical insomnia (WHIIRS score ≥ 9). Insomnia symptoms were most prevalent at baseline (p < 0.0001), but decreased significantly throughout follow-up (p < 0.001). However, 42% of participants still experienced insomnia symptoms 3 years after diagnosis. In multivariable models, older age (p = 0.02), hot flashes (p < 0.0001), and depressive symptoms (p < 0.0001) remained significantly associated with insomnia over time. CONCLUSIONS: Insomnia symptoms were most frequent closer to breast cancer diagnosis and treatment, but persisted for some women who were older and those reporting higher hot flashes and depressive symptoms. Survivorship care should include assessing insomnia symptoms, particularly during and immediately after primary treatment. Implementing early interventions for sleep problems may benefit young breast cancer survivors and improve their quality of life.

Prevalence and correlates of job and insurance problems among young breast cancer survivors within 18 months of diagnosis.

BACKGROUND: The prevalence and correlates of job and insurance problems were examined among a cohort of young U.S. breast cancer survivors during the first 18-months following diagnosis. METHODS: Participants were 708 women diagnosed at ≤45 years with stage I-III breast cancer. 90% were non-Hispanic white, 76% were married/partnered and 67% had ≥4-year college degree. Univariable and multivariable logistic regression examined the associations between demographic, lifestyle and clinical factors with job and insurance problems. RESULTS: 18-months after diagnosis, 56% of participants worked full-time, 16% part-time, 18% were homemakers and/or students, 4.5% were unemployed, and 2.4% were disabled. The majority (86%) had private insurance. Job-related problems were reported by 40% of women, and included believing they could not change jobs for fear of losing health insurance (35.0%), being fired (2.3%), and being demoted, denied promotion or denied wage increases (7.8%). Greater job-related problems were associated with being overweight vs. under/normal weight (p = 0.006), income <$50,000/per year (p = 0.01), and working full-time vs. part-time (p = 0.003). Insurance problems were reported by 27% of women, and included being denied health insurance (2.6%), health insurance increases (4.3%), being denied health benefit payments (14.8%) or denied life insurance (11.4%). Insurance problems were associated with being under/normal weight vs. obese (p = 0.01), not being on hormone therapy (p < 0.001), and a tumor size > 5 cm vs. < 2 cm (p = 0.01). CONCLUSIONS: Young survivors experienced significant job- and insurance-related issues following diagnosis. To the extent possible, work and insurance concerns should be addressed prior to treatment to inform work expectations and avoid unnecessary insurance difficulties.

Trajectories of depressive symptoms following breast cancer diagnosis.

BACKGROUND: This longitudinal study sought to identify groups of breast cancer survivors exhibiting distinct trajectories of depressive symptoms up to 24 months following diagnosis, and to describe characteristics associated with these trajectories. METHODS: A total of 653 women completed baseline questionnaires within 8 months of breast cancer diagnosis on patient characteristics, symptoms, and psychosocial variables. Depressive symptoms were assessed at baseline and 6, 12, and 18 months after baseline. Chart reviews provided cancer and treatment-related data. Finite mixture modeling identified trajectories of depressive symptoms measured with the Beck Depression Inventory (BDI). RESULTS: Six distinct trajectories were identified. Just over half of the sample had consistently very low (3.8%) or low (47.3%) BDI scores well below the traditional BDI cutoff point of 10 thought to be indicative of clinically significant depression; 29.2% had consistently borderline scores; 11.3% had initially high scores that declined over time, but remained above the cutoff point; 7.2% showed increased BDI over time; and a small but unique group (1.1%) reported chronically high scores above 25. Women in groups with lower depressive symptom levels were older, had less rigorous chemotherapy, fewer physical symptoms (fatigue and pain), and lower levels of illness intrusiveness. CONCLUSIONS: Approximately 20% of women had levels of depressive symptoms indicative of clinical depression that were maintained 2 years postdiagnosis. Factors related to trajectory membership such as illness intrusiveness, social support, fatigue, pain, and vasomotor symptoms suggest targets for possible intervention. IMPACT: Results demonstrate the heterogeneity of depressive symptoms following breast cancer and the need for continued screening posttreatment.

Trajectories of Posttraumatic Growth and Associated Characteristics in Women with Breast Cancer.

BACKGROUND: Cancer survivors may experience posttraumatic growth (PTG), positive psychological changes resulting from highly stressful events; however, the longitudinal course of PTG is poorly understood. PURPOSE: The purpose of the present study was to determine trajectories of PTG in breast cancer survivors and associated characteristics. METHODS: Women (N = 653) participating in a longitudinal observational study completed questionnaires within 8 months of breast cancer diagnosis and 6, 12, and 18 months later. Group-based modeling identified PTG trajectories. Chi-square tests and ANOVA detected group differences in demographic, medical, and psychosocial variables. RESULTS: Six trajectory groups emerged. Three were stable at different levels of PTG, two increased modestly, and one increased substantially over time. Trajectory groups differed by age, race, receipt of chemotherapy, illness intrusiveness, depressive symptoms, active-adaptive coping, and social support. CONCLUSIONS: This first examination of PTG trajectories in US cancer survivors elucidates heterogeneity in longitudinal patterns of PTG. Future research should determine whether other samples exhibit similar trajectories and whether various PTG trajectories predict mental and physical health outcomes.

Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study.

PURPOSE: To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women. PATIENTS AND METHODS: Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding. RESULTS: Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding. CONCLUSION: Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.

Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk.

INTRODUCTION: The tumor suppressor genes RASSF1A, APC, H-cadherin, RARbeta2, and cyclin D2 are methylated more frequently in breast cancer than in adjacent benign tissue. However, it is unclear whether promoter methylation of tumor suppressor genes in benign breast tissue is associated with an increased risk for breast cancer. METHODS: Promoter hypermethylation was measured in benign and malignant breast samples obtained by fine needle aspiration biopsy from 27 breast cancer patients and 55 unaffected women whose risk of breast cancer had been defined using the Gail, Claus, and BRCAPRO models. RESULTS: Cyclin D2 methylation occurred in 57% of tumor samples but not in corresponding benign breast samples and in only one sample from an unaffected patient (P < 0.0001). RARbeta2 methylation occurred in 32% of benign breast samples from cancer patients but only 9% of similar samples from unaffected women (P = 0.002). Promoter methylation of RASSF1A and APC occurred more frequently (70% and 56%, respectively) in unaffected women at high-risk for breast cancer as defined by the Gail model than in low/intermediate risk women (29% and 20%, P = 0.04 and P = 0.03). Of the Gail model risk factors, only number of prior breast biopsies was highly correlated with APC and RASSF1A methylation (P = 0.0001 and 0.02, respectively). CONCLUSIONS: Since cyclin D2 promoter methylation occurs almost exclusively in tumors, it may be possible to exploit it for the early detection of breast cancer. Promoter methylation of APC, RARbeta2, and RASSF1A in benign breast epithelium is associated with epidemiologic markers of increased breast cancer risk.

Circulating tumor cells in patients with breast cancer dormancy.

PURPOSE: The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy. EXPERIMENTAL DESIGN: We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy. RESULTS: Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours. CONCLUSIONS: The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.