Michelle J. Naughton

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.

Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481)

PURPOSE Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. METHODS In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. RESULTS Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17). CONCLUSION HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.

Phase II Study of Donepezil in Irradiated Brain Tumor Patients: Effect on Cognitive Function, Mood, and Quality of Life

PURPOSE A prospective, open-label phase II study was conducted to determine whether donepezil, a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimers type dementia, improved cognitive functioning, mood, and quality of life (QOL) in irradiated brain tumor patients. PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks, followed by a washout period of 6 weeks off drug. Outcomes were assessed at baseline, 12, 24 (end of treatment), and 30 weeks (end of wash-out). All tests were administered by a trained research nurse. RESULTS Of 35 patients who initiated the study, 24 patients (mean age, 45 years) remained on study for 24 weeks and completed all outcome assessments. All 24 patients had a primary brain tumor, mostly low-grade glioma. Scores significantly improved between baseline (pretreatment) and week 24 on measures of attention/concentration, verbal memory, and figural memory and a trend for verbal fluency (all P < .05). Confused mood also improved from baseline to 24 weeks (P = .004), with a trend for fatigue and anger (all P < .05). Health-related QOL improved significantly from baseline to 24 weeks, particularly, for brain specific concerns with a trend for improvement in emotional and social functioning (all P < .05). CONCLUSION Cognitive functioning, mood, and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil. Toxicities were minimal. We are planning a double blinded, placebo-controlled, phase III trial of donepezil to confirm these favorable results.

The Epidemiology of Arm and Hand Swelling in Premenopausal Breast Cancer Survivors

Background: Breast cancer survivors suffer from lymphedema of the arm and/or hand. Accurate estimates of the incidence and prevalence of lymphedema are lacking, as are the effects of this condition on overall quality of life. Methods: Six hundred twenty-two breast cancer survivors (age, ≤45 years at diagnosis) were followed with semiannual questionnaires for 36 months after surgery to determine the incidence of lymphedema, prevalence of persistent swelling, factors associated with each, and quality of life. Results: Of those contacted and eligible for the study, 93% agreed to participate. Fifty-four percent reported arm or hand swelling by 36 months after surgery, with 32% reporting persistent swelling. Swelling was reported to occur in the upper arm (43%), the hand only (34%), and both arm and hand (22%). Factors associated with an increased risk of developing swelling included having a greater number of lymph nodes removed [hazards ratio (HR), 1.02; P < 0.01], receiving chemotherapy (HR, 1.76; P = 0.02), being obese (HR, 1.51 versus normal weight; P = 0.01), and being married (HR, 1.36; P = 0.05). Factors associated with persistent swelling were having more lymph nodes removed (odds ratio, 1.03; P = 0.01) and being obese (odds ratio, 2.24 versus normal weight; P < 0.01). Women reporting swelling had significantly lower quality of life as measured by the functional assessment of cancer therapy-breast total score and the SF-12 physical and mental health subscales (P < 0.01 for each). Conclusions: Lymphedema occurs among a substantial proportion of young breast cancer survivors. Weight management may be a potential intervention for those at greatest risk of lymphedema to maintain optimal health-related quality of life among survivors. (Cancer Epidemiol Biomarkers Prev 2007;16(4):775–82)

A critical review of dimension-specific measures of health-related quality of life in cross-cultural research

This article reviews six dimension-specific health-related quality of life (HRQL) measures which have been used cross-culturally. The instruments reviewed are: the Beck Depression Inventory (BDI); the McGill Pain Questionnaire (MPQ); the Center for Epidemiologic Studies—Depression (CES-D); the Zung Self-Rating Depression Scale (SDS); the General Health Questionnaire (GHQ); and the Psychological General Well-Being Index (PGWB). These instruments primarily represent the psychological or emotional dimension of HRQL, and are scales that were developed and validated in the USA, Canada or the UK. The review of specific studies for each of the six instruments was not meant to be exhaustive, but rather to give an indication of the ways in which the instruments have been assessed or used in various countries. The focus throughout this article is on the psychometric properties (reliability, validity and responsiveness) of these scales in different cultures, as well as the processes used to translate the instruments from English into another language. Implications of the results of this review for cross-cultural use of dimension-specific HRQL instruments are drawn.

Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the women's health initiative randomized trial

Further analyses from the Womens Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.

Reliability and Validity of the Women's Health Initiative Insomnia Rating Scale

The reliability and construct validity of the 5-item Womens Health Initiative Insomnia Rating Scale (WHIIRS) were evaluated in 2 studies. In Study 1, using a sample of 66,269 postmenopausal women, validity of the WHIIRS was assessed by examining its relationship to other measures known to be related to sleep quality. Reliability of the WHIIRS was estimated using a resampling approach; the mean alpha coefficient was .78. Test-retest reliability coefficients were .96 for same-day administration and .66 after a year or more. Correlations of the WHIIRS with the other measures were in the predicted directions. Study 2 used a sample of 459 women and compared the WHIIRS with objective indicators of sleep quality. Results showed that differences in the objective indicators could be detected by the WHIIRS. Findings suggest that a between-group mean difference of approximately 0.50 of a standard deviation on the WHIIRS may be clinically meaningful.

Sleep Duration and Risk of Ischemic Stroke in Postmenopausal Women

Background and Purpose— Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed. Methods— We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Womens Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics. Results— At baseline, 8.3% of subjects had reported their sleep duration as ≤5 hours per night and 4.6% reported long duration of sleep (≥9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting ≤6, 8, and ≥9 hours of sleep. A modestly stronger association with sleep duration ≤6 hours per night (RR, 1.22; 1.03, 1.44) was noted among women without prevalent cardiovascular disease at baseline. Our analyses also reveal that the adverse effect of long sleep is likely independent of the increased risk for ischemic stroke associated with frequent snoring and sleepiness (RR, 1.31; 1.00, 1.72). Conclusions— Habitual sleep patterns are important neurobehavioral determinants of risk for ischemic stroke in postmenopausal women. The underlying neurobiology and mechanistic mediators for the putative adverse effect of long sleep (≥9 hours/night) need further elucidation.

Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study

Objective To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms (hot flashes and night sweats) in peri- and postmenopausal women. Design A double-masked, randomized, controlled, clinical trial was conducted. A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were randomized into one of three groups. In all groups, participants consumed a daily supplement containing 25 g of soy protein and were randomly assigned to one of three groups: (a) isoflavone extracted soy protein (control), (b) soy protein with a medium dose of isoflavones (42 mg/day), or (c) soy protein with a higher dose of isoflavones (58 mg/day). The primary outcome measure in this trial was change in reported vasomotor symptoms. Results A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups. No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone, middle isoflavone, or control groups. The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy. Conclusions These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women.

Health-related quality of life of children and adolescents with type 1 or type 2 diabetes mellitus: SEARCH for Diabetes in Youth Study.

OBJECTIVE To examine the associations between demographic and diabetes management variables and the health-related quality of life (HRQOL) of youths with type 1 or type 2 diabetes mellitus (DM). DESIGN Cross-sectional study. SETTINGS Selected populations in Ohio, Washington, South Carolina, Colorado, Hawaii, and California; health service beneficiaries in 3 American Indian populations; and participants in the Pima Indian Study in Arizona. PARTICIPANTS Two thousand four hundred forty-five participants aged 8 to 22 years in the SEARCH for Diabetes in Youth Study. MAIN OUTCOME MEASURE Pediatric Quality of Life Inventory scores. RESULTS Among youths with type 2 DM, HRQOL was lower compared with those with type 1. Among those with type 1 DM, worse HRQOL was associated with a primary insurance source of Medicaid or another government-funded insurance, use of insulin injections vs an insulin pump, a hemoglobin A(1c) value of at least 9%, and more comorbidities and diabetes complications. There was a significant age x sex interaction, such that, in older groups, HRQOL was lower for girls but higher for boys. For youths with type 2 DM, injecting insulin at least 3 times a day compared with using an oral or no diabetes medication was associated with better HRQOL, and having 2 or more emergency department visits in the past 6 months was associated with worse HRQOL. CONCLUSIONS Youths with types 1 and 2 DM reported HRQOL differences by type of treatment and complications. The significant age x sex interaction suggests that interventions to improve HRQOL should consider gender differences in diabetes adjustment and management in different age groups.