BACKGROUND

The purpose of this study was to determine whether women participating in the Women’s Healthy Eating and Living (WHEL) Study, exhibited similar dietary changes, second breast cancer events, and overall survival regardless of race/ethnicity.

METHODS

This secondary analysis used data from 3013 women self-identifying as Asian Americans, African American, Hispanic, or white and who were randomly assigned to a dietary intervention or comparison group. Changes in dietary intake over time by race/ethnicity and intervention status were examined using linear mixed-effects models. Cox proportional hazards models were used to examine the effects of the intervention on the occurrence of second breast cancer events and overall survival. Statistical tests were 2-sided.

RESULTS

African Americans and Hispanics consumed significantly more calories from fat (+3.2%) and less fruit (−0.7 servings/day) than Asians and whites at baseline (all P < 0.01). Overall, intervention participants significantly improved their dietary pattern from baseline to the end of year 1: reducing calories from fat by 4.9% and increasing intake of fiber (+6.6 grams/day), fruit (+1.1 servings/day), and vegetables (+1.6 servings/day) (all P < 0.05). Despite improvements in the overall dietary pattern of these survivors, the intervention did not significantly influence second breast cancer events and overall survival.

CONCLUSIONS

Overall, all racial groups significantly improved their dietary pattern over time, but the maintenance of these behaviors were lower among African American women. More research and larger minority samples are needed to determine the specific factors that improve breast cancer-specific outcomes in diverse populations of survivors.

Hypothesis

Self-reported use of complementary and alternative medicine (CAM) has been shown to increase following a cancer diagnosis, and breast cancer survivors are the heaviest users among cancer survivors. The aim of this study was to determine whether the prevalence estimate of CAM use varied according to classification of CAM. We used a comprehensive system to classify CAM users and test differences in demographic, lifestyle, quality of life, and cancer characteristics among them.

Study Design and Methods

Participants were 2562 breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study, aged 28-74 years. A structured telephone interview assessed CAM use, questioning about specific CAM practices, and whether use was related to cancer. We examined CAM use in relation to demographics, health behaviors, and quality of life.

Results

Approximately 80% of the women used CAM for general purposes but only 50% reported CAM use for cancer purposes. Visual imagery, spiritual healing, and meditation were the most frequently used practices for cancer purposes. CAM use, defined as consulting a CAM practitioner and regular use, was significantly related to younger age, higher education, increased fruit & vegetable intake, and lower body mass index (p < .05). CAM users who had seen a practitioner were also more likely to report poor physical and mental health than non-CAM users (p < .05). CAM use was not associated with changes in physical and mental health between study baseline and 1-year follow-up.

Conclusion

This study addressed important differences in the classification of CAM use among breast cancer survivors. Future studies need to further test the potential benefits and risks associated with CAM use.

Purpose

Physical health-related quality of life scores have been, inconsistently, associated with breast cancer prognosis. This analysis examined whether change in physical health scores were related to outcomes in women with a history of breast cancer.

Methods

2343 breast cancer survivors in a randomized diet trial provided self-reported assessment of physical health-related quality of life at baseline and year 1. Based on change in physical health score, participants were grouped into subpopulations of decreased physical health, no/minimal changes, and increased physical health. Cox regression analysis assessed whether change in physical health (from baseline to year 1) predicted disease-free and overall survival; hazard ratio (HR) was the measure of association.

Results

There were 294 additional breast cancer events and 162 deaths among women followed for 7.3 years. Improvements in physical health were associated with younger age, lower BMI, being employed, not receiving tamoxifen, lower physical activity, and lower baseline physical and mental health. There was no association of change in physical health with additional breast cancer events or mortality among women diagnosed ≤ 2 years before study enrollment. However, among women who entered the study >2 years post diagnosis, the HR for increased compared to decreased physical health was 0.38 (95% CI, 0.16 to 0.85) for all-cause mortality.

Conclusions

These results appear to support testing an intervention to improve physical health in breast cancer patients among patients after the acute stage of treatment.

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen, and to examine potential correlates of endoxifen concentrations including CYP2D6 metabolizer phenotype and body mass index (BMI). Tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen concentrations were measured from 1370 estrogen receptor positive breast cancer patients participating in the Women’s Healthy Eating and Living (WHEL) Study, and tested for associations with breast cancer outcomes. Breast cancer outcomes were not associated with tamoxifen, 4-hydroxytamoxifen or N-desmethyltamoxifen concentrations. For endoxifen, a threshold was identified suggesting that women in the upper four quintiles of endoxifen had a 26% lower recurrence rate than women in the bottom quintile. (HR=0.74; 95% CI, [0.55, 1.00]). Predictors of membership in this higher risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and low tamoxifen concentrations. This study suggests a minimal threshold at which endoxifen is effective against breast cancer recurrence, which 80% of tamoxifen-takers achieve.

Background

We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women’s Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations.

Methods

Baseline and year one concentrations of total and bioavailable estradiol and testosterone and sex hormone binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, anti-estrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use.

Results

Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm vs. 42 (18.9%) in the comparison arm (p=0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00-2.84; p=0.049). There were significant interactions between the intervention and total (p=0.015) and bioavailable (p=0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2-0.7) or bioavailable (HR 0.4, 95%CI: 0.2-0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4-1.5) or bioavailable (HR 0.8, 95%CI: 0.4-1.5) testosterone. No significant effects were seen for estradiol or SHBG.

Conclusions

The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone.

Impact

Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence.

Background

Previous studies examining the relationship between micronutrient intakes and survival following diagnosis of breast cancer have reported mixed results. This may be partly due to considerable variance in amounts of micronutrients consumed from diet and supplements across studies.

Methods

Early stage breast cancer survivors (n=3081) completed four 24-hour dietary and supplement recalls at the baseline assessment (1995 to 2000) and were followed for a median of 9.0 years. Mean micronutrient intakes were compared to dietary reference intakes (DRI) to assess micronutrient adequacy for both users and non-users of supplements. Cox regressions were performed to assess whether intakes of selected micronutrients were associated with all-cause mortality.

Results

412 deaths occurred between baseline and August 2009. Among these women, more supplement users had adequate micronutrient intakes than non-users for 15 out of 17 micronutrients. Less than 10% of supplement users (< 2% of non-supplement users) reported levels that exceeded the tolerable upper limit for each micronutrient except magnesium. After adjusting for age, tumor characteristics, and health status variables, micronutrient intakes were not significantly associated with all-cause mortality.

Conclusion

Dietary supplements may improve overall micronutrient intakes of breast cancer survivors. However, vitamin and mineral intakes were not associated with all-cause mortality.

Background

Health-related quality of life (HRQOL) has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors.

Methods

Women with early stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association.

Results

There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01–10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psycho-social variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher BMI, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all).

Conclusion

Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.

Goals of Work

The goal of this study was to examine the relationship between menopausal symptoms, sleep quality and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer.

Patients and Methods

Data on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12 weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre-Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri-Peri); post-menopausal before and after chemotherapy (Post-Post).

Main Results

Results suggested that women within the Pre-Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre-Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri-Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep.

Conclusions

Contrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings.

Purpose

Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis.

Methods

Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival.

Results

Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk.

Conclusion

Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted.

Dietary intervention trials aim to change dietary patterns of individuals. Participating in such trials could impact dietary self-report in divergent ways: Dietary counseling and training on portion-size estimation could improve self-report accuracy; participant burden could increase systematic error. Such intervention-associated biases could complicate interpretation of trial results. The authors investigated intervention-associated biases in reported total carotenoid intake using data on 3,088 breast cancer survivors recruited between 1995 and 2000 and followed through 2006 in the Women's Healthy Eating and Living Study, a randomized intervention trial. Longitudinal data from 2 self-report methods (24-hour recalls and food frequency questionnaires) and a plasma carotenoid biomarker were collected. A flexible measurement error model was postulated. Parameters were estimated in a Bayesian framework by using Markov chain Monte Carlo methods. Results indicated that the validity (i.e., correlation with “true” intake) of both self-report methods was significantly higher during follow-up for intervention versus nonintervention participants (4-year validity estimates: intervention = 0.57 for food frequency questionnaires and 0.58 for 24-hour recalls; nonintervention = 0.42 for food frequency questionnaires and 0.48 for 24-hour recalls). However, within- and between-instrument error correlations during follow-up were higher among intervention participants, indicating an increase in systematic error. Diet interventions can impact measurement errors of dietary self-report. Appropriate statistical methods should be applied to examine intervention-associated biases when interpreting results of diet trials.

Background

Both alcohol consumption and obesity have been linked with breast cancer morbidity and mortality. An inverse association between alcohol intake and obesity suggests possible confounding between these variables (and perhaps other factors) with breast cancer outcomes.

Methods

Alcohol intake (beer, wine, spirits, and total) was examined in 3088 women previously diagnosed and treated for breast cancer, within an intervention trial that targeted vegetables, fiber, and fat but not alcohol or weight loss. Factors associated with baseline alcohol intake were included in Cox proportional hazards models for recurrence and mortality.

Results

Alcohol intake was significantly associated with higher education and physical activity levels. Neither light alcohol intake nor obesity was significantly associated with breast cancer recurrence, but moderate alcohol intake > 300 g/month was protective against all-cause mortality (HR = 0.69, CI=0.49-0.97) in a proportional hazards model adjusted for obesity. Obese women were 61% more likely to be nondrinkers than drinkers, and 76% more likely to be light drinkers than moderate/heavy drinkers. In non-obese women, alcohol intake > 10 g/month was associated with lower risk of all-cause mortality (HR = 0.68, 95% CI = 0.51-0.91).

Conclusion

Light alcohol intake, regardless of body weight, did not increase the risk of breast cancer recurrence or all-cause mortality in this cohort of middle-aged women previously diagnosed with breast cancer. Alcohol intake was associated with other favorable prognostic indicators that may explain its apparent protective effect in non-obese women.

Objective

Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.

Methods

A total of 2,361 post-treatment breast cancer survivors (Stage I–III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate–vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.

Results

Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.

Conclusions

Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.

Objective

Patients with Alzheimer's disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA.

Methods

A randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after three weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed.

Results

Fifty-two participants (mean age=77.8 years, SD=7.3) with AD and OSA were included.

After one treatment night, the tCPAP group had significantly less % Stage 1 (p=0.04) and more % Stage 2 sleep (p=0.02) when compared to the pCPAP group. In the paired analysis, 3-weeks of tCPAP resulted in significant decreases in WASO (p=0.005), % Stage 1 (p=0.001), arousals (p=0.005), and in an increase in % Stage 3 (p=0.006).

Conclusion

In mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for three weeks.

Purpose

Patients with malignancy sometimes develop painful mucositis and require patient-controlled analgesia (PCA) to treat their pain. Pain disrupts sleep and there is some evidence that analgesic medications also disrupt sleep. This study examined whether treatment with the sedative hypnotic eszopiclone could improve self-reports of sleep, fatigue, and pain as well as decrease opioid self-administered via PCA.

Methods

Inpatients who developed mucositis severe enough to require PCA treatment were randomized double-blind to a 2-day trial on eszopiclone or placebo-administered at bedtime. Patients completed questionnaires which assessed sleep, pain, and fatigue. PCA medication was calculated in terms of morphine equivalents. Data were analyzed with unpaired t tests and repeated measures analysis of variance.

Results

Twenty-two patients were randomized to placebo and 23 to eszopiclone. Groups were comparable in age and treatment characteristics. Mean pain scores were lower in the eszopiclone group at all time points (morning p = 0.01, afternoon p = 0.04, evening p = 0.04). The eszopiclone group reported increased sleep time (p < 0.05), fewer nighttime awakenings (p < 0.001), better self-reported sleep quality (p = 0.01), and depth (p = 0.04). There were no significant differences between eszopiclone and placebo in terms of self-reports of fatigue or opioid usage.

Conclusion

Sedative hypnotic agents improve sleep and analgesia even in the setting of considerable pain and discomfort.

Purpose

Estimates of insomnia in breast cancer patients are high, with reports of poor sleep lasting years after completion of cancer treatment. This randomized controlled crossover pilot study looked at the effects of individual cognitive behavioral therapy for insomnia (IND-CBT-I) on sleep in breast cancer survivors.

Patients and methods

Twenty-one participants were randomly assigned to either a treatment group (six weekly IND-CBT-I sessions followed by six weeks of follow up) or a delayed treatment control group (no treatment for six weeks followed by six weekly IND-CBT-I sessions). Of these, 14 participants completed the pilot study (six in the treatment group and eight in the delayed treatment control group).

Results

Self-rated insomnia was significantly improved in the treatment group compared to the waiting period in the delayed treatment control group. The pooled pre–post-IND-CBT-I analyses revealed improvements in self-rated insomnia, sleep quality, and objective measures of sleep.

Conclusions

These preliminary results suggest that IND-CBT-I is appropriate for improving sleep in breast cancer survivors. Individual therapy in a clinic or private practice may be a more practical option for this population as it is more easily accessed and readily available in an outpatient setting.

Although neighborhood disadvantage has been linked to the development of cardiovascular disease, the mechanism through which living in impoverished neighborhoods is associated with poor cardiovascular health is not well understood. Additionally, it is not clear whether individual socioeconomic status (SES) interacts with neighborhood factors to influence cardiovascular outcomes. Using multilevel modeling, we examined the interaction between neighborhood poverty and individual SES on pressor responses to an alpha agonist, Phenylephrine (PE), in an adult sample of 105 African-Americans and 106 Caucasian-Americans. Neighborhood poverty was assessed using census block data gathered from the Census Bureau. Education and occupation were used to assess individual SES. Pressor responsiveness was calculated as the systolic and diastolic blood pressure (BP) response to a 100-microgram PE bolus administered intravenously. There was a significant interaction between education and neighborhood poverty on pressor responses. Higher education was associated with smaller BP responses to PE; but only in individuals who lived in neighborhoods in which less than 5% of the residents lived below the poverty line. Occupation was unrelated to pressor responses to PE. These results suggest that neighborhood characteristics play an important role in cardiovascular functioning.

This study characterized sleep in heart failure (HF) and determined associations with quality of life. Forty stable HF patients and 34 healthy volunteers were studied in a clinical research unit. HF patients had more central apneas/hour [17.6 vs. 5.4 (p≤0.01)] and obstructive apneas/hour [21.7 vs. 8.5 (p≤0.05)], spent more time in stage 1 sleep [54 min. vs. 35 min. (p≤.05)] and had more respiratory awakenings following apneic events [27.2 vs. 4.2 (p≤.01)]. More HF patients were depressed (55% vs. 27.2%, p≤0.01) and had worse fatigue (p≤0.05). In multiple regression analysis, physical functioning quality of life was predicted by reduced LVEF (p≤0.05), shorter distance on a six-minute walk test (p≤.05), greater fatigue (p≤0.01), and more apneas (p’s≤0.05) (model R2 =.672, p≤0.001). Emotional functioning quality of life was predicted by greater fatigue (p≤0.01) (model adjusted R2 =.732, p<0.001). Findings provide evidence that in addition to functional status and ongoing fatigue, poorer quality of life in HF is independently related to the severity of sleep-disordered breathing.

Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995–2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies.

Goals of work

The goal of this study was to examine the relationship between menopausal symptoms, sleep quality, and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer.

Patients and methods

Data on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12 weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses, participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre–Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri–Peri), and post-menopausal before and after chemotherapy (Post–Post).

Main results

Results suggested that women within the Pre–Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre–Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri–Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep.

Conclusions

Contrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings.

Epidemiologic research focuses on estimating exposure-disease associations. In some applications the exposure may be dichotomized, for instance when threshold levels of the exposure are of primary public health interest (e.g., consuming 5 or more fruits and vegetables per day may reduce cancer risk). Errors in exposure variables are known to yield biased regression coefficients in exposure-disease models. Methods for bias-correction with continuous mismeasured exposures have been extensively discussed, and are often based on validation substudies, where the “true” and imprecise exposures are observed on a small subsample. In this paper, we focus on biases associated with dichotomization of a mismeasured continuous exposure. The amount of bias, in relation to measurement error in the imprecise continuous predictor, and choice of dichotomization cut point are discussed. Measurement error correction via regression calibration is developed for this scenario, and compared to naïly using the dichotomized mismeasured predictor in linear exposure-disease models. Properties of the measurement error correction method (i.e., bias, mean-squared error) are assessed via simulations.

Objective

The concept of symptom clusters is relatively new in cancer patients' symptom management. This study, which spanned four cycles of chemotherapy, combined three commonly seen pre-treatment symptoms in cancer patients (i.e., sleep disturbances, fatigue and depression) into one symptom cluster, to explore the associations between pre-treatment cluster categories and longitudinal profiles of these same symptoms during chemotherapy.

Methods

This was a prospective study. Seventy-six women with newly diagnosed stage I–III breast cancer, scheduled to receive at least four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy participated. Data were collected at seven time points before and during treatment. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Fatigue was measured with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Depressive symptoms were measured with the Center of Epidemiological Studies-Depression (CES-D). Patients were divided into three groups based on the number of symptoms they experienced before the start of chemotherapy (i.e., no symptoms, 1–2 symptoms or all three symptoms) and a symptom cluster index (SCI) was computed.

Results

All women reported worse sleep, more fatigue and more depressive symptoms during treatment compared to baseline (all p's <0.01); however, those women with a higher symptom cluster index (i.e., more symptoms pre-treatment) continued to experience worse symptoms during treatment compared to those who began with fewer symptoms (all p's <0.01).

Conclusions

A higher clinically relevant-based pre-treatment symptom cluster was associated with more sleep disturbances, greater fatigue and more depressive symptoms during chemotherapy. Specific interventions for these pre-treatment symptoms may improve the frequency and severity of these same symptoms during chemotherapy, when they are most severe and most disruptive to quality of life.

In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit, and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4 and 6 years and breast cancer-free survival in the Women’s Healthy Eating and Living (WHEL) Study participants (n = 3043), who had been diagnosed with early stage breast cancer. The primary endpoint was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve (AUC) formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared to the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval 0.54–0.83) after adjustment. The interaction between study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.

Purpose

To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment.

Patients and Methods

A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines.

Results

Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002).

Conclusion

A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.

Epidemiologic research focuses on estimating exposure-disease associations. In some applications the exposure may be dichotomized, for instance when threshold levels of the exposure are of primary public health interest (e.g., consuming 5 or more fruits and vegetables per day may reduce cancer risk). Errors in exposure variables are known to yield biased regression coefficients in exposure-disease models. Methods for bias-correction with continuous mismeasured exposures have been extensively discussed, and are often based on validation substudies, where the “true” and imprecise exposures are observed on a small subsample. In this paper, we focus on biases associated with dichotomization of a mismeasured continuous exposure. The amount of bias, in relation to measurement error in the imprecise continuous predictor, and choice of dichotomization cut point are discussed. Measurement error correction via regression calibration is developed for this scenario, and compared to naïvely using the dichotomized mismeasured predictor in linear exposure-disease models. Properties of the measurement error correction method (i.e., bias, mean-squared error) are assessed via simulations.

SUMMARY

In epidemiologic studies of exposure-disease association, often only a surrogate measure of exposure is available for the majority of the sample. A validation sub-study may be conducted to estimate the relation between the surrogate measure and true exposure levels. In this article, we discuss three methods of estimation for such a main study / validation study design: (i) maximum likelihood (ML), (ii) multiple imputation (MI) and (iii) regression calibration (RC). For logistic regression, we show how each method depends on a different numerical approximation to the likelihood, and we adapt standard software to compute both multiple imputation and maximum likelihood estimates. We use simulation to compare the performance of the estimators for both realistic and extreme settings, and for both internal and external validation designs. Our results indicate that with large measurement error or large enough sample sizes, ML performs as well or better than MI and RC. However, for smaller measurement error and small sample sizes, either ML or RC may have the advantage. Interestingly, in most cases the relative advantage of RC versus ML was determined by the relative variance rather than bias of the estimators. Software code for all three methods in SAS is provided.