Soluble fiber and the physical state of fruits/vegetables affect plasma ß-carotene concentrations; however, most of this research was conducted in laboratory-based settings. These analyses investigated the relationship between soluble fiber and juiced vs. whole fruits/vegetables to plasma ß-carotene concentrations in a free-living population.
This cross-sectional analysis used 12-month follow-up data from the Women’s Healthy Eating & Living Study (WHEL) (1995-2006), a study to improve diet in breast cancer survivors in the Western United States. The dietary nutrients considered in this analysis included intake of soluble fiber (g), ß-carotene from fruit/vegetable juice (mg), and ß-carotene from whole fruits/vegetables (mg). A linear regression model was used to assess the relationship of the variables to plasma ß-carotene concentrations.
Out of 3,088 women enrolled in WHEL 2,397 women had complete data (mean age=54). The final model accounted for approximately 49% of the explained variance in plasma ß-carotene concentrations. Fruit/vegetable juice had the largest, positive relation to plasma ß-carotene concentrations (standardized parameter estimate=0.23, p < 0.01) followed by whole fruits/vegetables (standardized parameter estimate=0.09, p < 0.01). Conclusion: Soluble fiber may inhibit ß-carotene absorption; therefore, consumption of juice may increase plasma ß-carotene concentrations more than whole fruits/vegetables in free-living populations.
Dietary fiber; carotenoids; antioxidants; diet; food
The purpose of this study was to assess whether CAM use affected breast cancer prognosis in those who did not receive systemic therapy.
Secondary data analysis of baseline/survey data from the Women's Healthy Eating and Living Study (WHEL). 2562 breast cancer survivors participating in the study completed baseline assessments and a CAM use questionnaire. Cox regression models were conducted to evaluate the use of CAM modalities and dietary supplements on time to an additional breast cancer event (mean follow-up = 7.3 years).
A US-based multi-site randomized dietary trial.
Time to additional breast cancer events.
The women who did not receive any systemic treatment had a higher risk for time to additional breast cancer events (HR=1.9, 95% CI: 1.32, 2.73) and for all-cause mortality (HR=1.7, 95% CI: 1.06, 2.73) compared to those who had received systemic treatment. Among 177 women who did not receive systemic treatment, CAM use was not significantly related to additional breast cancer events. There were no significant differences between high supplement users ( ≥ 3 formulations per day) and low supplement users in either risk for additional breast cancer events.
The risk for an additional breast cancer event and/or death was higher for those who did not receive any systemic treatments; the use dietary supplements or CAM therapies did not change this risk. This indicates that complementary and alternative therapies did not alter the outcome of breast cancer and should not be used in place of standard treatment.
breast cancer; complementary and alternative medicine; dietary supplements; long- term prognosis; alternative cancer treatment
Health-related quality of life (HRQOL), body mass index (BMI), and physical activity (PA) levels have all been associated with prognosis following breast cancer and may partially explain higher mortality for breast cancer in certain race/ethnic sub-groups. In this study, we examined associations between PA, BMI, and HRQOL by race in a sample of breast cancer survivors.
Measures of PA, BMI, and HRQOL as well as demographic and medical characteristics of women (N=3013, 13% nonwhite) who participated in the Women’s Healthy Eating and Living Study were assessed at baseline. Analysis of covariance was used to examine the relationship between PA and obesity with HRQOL outcomes. Statistical tests were two-sided.
African-American women were less likely to meet guidelines for PA and more likely to be obese than women from other ethnic groups (P < 0.05). In adjusted models, women who met guidelines for PA reported significantly higher physical health composite (point differences ranged from 10.5 to 21.2 points, all P <0.05) and vitality (point differences ranged from 9.9 to 16.5 points, all P <0.05) scores than those who did not, regardless of race/ethnicity. Associations between obesity and HRQOL were mixed with fewer associations for Asian-American and African-American women and stronger associations for whites.
Breast cancer survivors from racially and ethnically diverse populations have lower levels of PA and higher rates of obesity that are generally associated with poorer HRQOL. Culturally sensitive PA and weight loss interventions may improve these lifestyle characteristics and result in improved HRQOL.
breast neoplasm; African American; disparities; Hispanic; obesity; quality of life; cancer survivors
After successful treatment of early breast cancer, many women still report pain symptoms, and attribute them to the previous illness or its treatment. However, knowledge about the long-term course of pain in breast cancer is limited.
Baseline assessment included 3,088 women who received a breast cancer diagnosis on average 2 years prior to enrollment, and who completed typical medical treatments. After 4 years, a subsample of 2,160 recurrence-free women (70%) was re-assessed. The major outcome variable was the composite index for general pain symptoms.
Over the 4 year course, a slight but significant increase in pain was reported. If only medical variables were examined, a triple interaction between surgery type, breast cancer stage, and time indicated that pain scores increased in most subgroups, while they decreased in stage II women after mastectomy and stage III women after lumpectomy. Using a regression analytical approach, psychological and other variables added significantly to the prediction of pain persistence. Regression analysis revealed that pain symptoms increased in those women taking tamoxifen at baseline, in those reporting depression at baseline or stressful life events during the first 12 months after enrollment. Exercise at baseline had a beneficial effect on pain recovery.
The persistence or increase of pain symptoms in women surviving breast cancer is associated with some medical factors (surgery type, tamoxifen use), but also with psychological factors. Pain should be a standard outcome variable in the evaluation of cancer treatment programs.
breast cancer; pain; depression; physical exercise
Young adult cancer survivors are often unaware of their fertility status and uninformed regarding their fertility and fertility preservation options. This qualitative research study explores the fertility and parenthood concerns of reproductive-age female cancer survivors and how they make parenthood decisions.
Population- and clinic-based recruitment methods were used to identify a diverse group of survivors between the ages of 18 and 34 years. Our final sample size included 22 participants who attended one of seven focus groups. We used cross-case, inductive analysis to identify themes.
The following main themes were identified: (1) A hopeful but worried approach to fertility and parenthood, (2) Frustration with a lack of choice or control over fertility, (3) Young survivors want information about their fertility, (4) Young survivors want better continuity of care in survivorship, (5) Cancer diagnosis and related fertility problems introduce relationship challenges, and (6) Decisions about parenthood are complicated.
The diverse group of young cancer survivors in this study identified several common needs and concerns regarding fertility and parenthood. This study illustrates that young survivors could benefit from improved information regarding their fertility and parenthood options throughout survivorship, better coordination of medical care, and support navigating many emotional and practical issues that arise when considering their reproductive and parenthood options.
Fertility; Parenthood; Reproduction; Cancer; Survivorship; Adolescent; Young adult
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.
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.
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.
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.
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.
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.
Dietary supplements may improve overall micronutrient intakes of breast cancer survivors. However, vitamin and mineral intakes were not associated with all-cause mortality.
dietary intake; supplement use; breast cancer survival
Observational studies demonstrate an association between physical activity and improved outcomes in breast and colon cancer survivors. To test these observations with a large, randomized clinical trial, an intervention that significantly impacts physical activity in these patients is needed. The Active After Cancer Trial (AACT) was a multicenter pilot study evaluating the feasibility of a telephone-based exercise intervention in a cooperative group setting.
Sedentary (engaging in < 60 minutes of recreational activity/week) breast and colorectal cancer survivors were randomized to a telephone-based exercise intervention or usual care control group. The intervention was delivered through the University of California at San Diego; participants received 10 phone calls over the course of the 16-week intervention. All participants underwent assessment of physical activity, fitness, physical functioning, fatigue and exercise self-efficacy at baseline and after the 16-week intervention.
One hundred and twenty-one patients were enrolled through 10 Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Participants randomized to the exercise group increased physical activity by more than 100%, vs. 22% in controls (54.5 vs. 14.6 minutes, p=0.13), and experienced significant increases in fitness (increased 6-minute walk test distance by 186.9 vs. 81.9 ft, p=0.006) and physical functioning (7.1 vs. 2.6, p=0.04) as compared to the control group.
Breast and colorectal cancer survivors enrolled in a multicenter, telephone-based physical activity intervention increased physical activity and experienced significant improvements in fitness and physical functioning. Lifestyle intervention research is feasible in a cooperative group setting.
Breast cancer; exercise; cooperative group; intervention; physical functioning
Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of post-diagnostic weight variation on survival, we examined the relationship by comorbid status and initial BMI.
The current analysis included 12,915 breast cancer patients diagnosed between 1990 and 2006 with Stage I–III tumors from four prospective cohorts in the US and China Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of five weight change categories (within <5% [reference]; 5–<10% and ≥10% loss and gain) with mortality were estimated using Cox proportional hazards models.
Mean weight change was 1.6 kg. 14.7% of women lost and 34.7% gained weight. Weight stability in the early years post-diagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR=1.41; 95% CI: 1.14, 1.75) in the US and over three times the risk of death (HR=3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by pre-diagnosis BMI, and in the US lower survival were seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a non-significant increased risk of death.
Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality.
Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.
Younger women diagnosed with breast cancer are more likely to have survival concerns related to fertility, which may influence their treatment decisions.
This qualitative study explores how young women make cancer treatment decisions and the role of fertility concerns in that process.
We used purposeful sampling to identify a diverse group of 20 young breast cancer survivors, half of whom had a child after breast cancer. We conducted open-ended telephone interviews and used cross-case, inductive analysis to identify themes.
The main themes were: 1) I was young, I wanted to do everything possible to move forward with my life and not to have the cancer come back, 2) Fertility concerns are different for every woman 3) My oncologist was great… a huge part of my survivorship, and 4) They didn’t tell me about my options and I didn’t think about fertility until it was too late.
While fertility was important to many participants, treatment decisions were mainly motivated by survival concerns. Fertility concerns depended on life circumstances and the timing in relation to diagnosis varied. There is a need for improved information regarding the impact of treatment on fertility and fertility preservation options, even if concerns are not expressed at diagnosis.
Implications for Practice
It is critical that cancer care providers provide timely information regarding fertility. Oncology nurses are particularly well-positioned to serve this role by communicating with patients about their fertility concerns and reproductive planning prior to treatment and throughout the course of survivorship.
breast cancer; young women; qualitative; treatment decisions; fertility
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.
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.
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.
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.
Obese and underweight women who develop breast cancer may have poorer survival compared to normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990-2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30-<35 kg/m2), severely obese (35-<40 kg/m2), and morbidly obese (≥40 kg/m2) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR=1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR=1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared to normal-weight (18.5-24.9 kg/m2) women. Severe obesity (HR=1.09; 95% CI: 0.88, 1.36) and obesity (HR=1.11; 95% CI: 0.97, 1.27) were related to small, non-significant increased risks. Overweight (25.0-29.9 kg/m2) was not associated with any excess risk compared to normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival.
body mass index; weight; obesity; breast cancer; survival; prognosis; mortality
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.
bias (epidemiology); diet; intervention studies; Markov chain Monte Carlo; measurement error; nutrition assessment; reproducibility of results; validity
Breast cancer diagnosis and treatment can negatively impact fertility in premenopausal women and influence reproductive planning. This study investigates whether concerns about reproduction after breast cancer treatment were associated with long-term depressive symptoms.
Patients and Methods
Participants include 131 women diagnosed with early-stage breast cancer at age 40 or younger participating in the Women's Healthy Eating and Living (WHEL) Survivorship Study. Participants were enrolled an average of 1.5 years post-diagnosis and depressive symptoms were monitored 6 times throughout the average additional 10 year follow-up period. Detailed recall of reproductive concerns after treatment was collected an average of 12 years post-diagnosis. Multilevel regression was used to evaluate whether mean long-term depressive symptoms differed as a function of reproductive concerns and significant covariates.
Multilevel regression identified greater recalled reproductive concerns as an independent predictor of consistent depressive symptoms after controlling for both social support and physical health (B= 0.02, SE= 0.01, p=0.04). In bivariate analyses, being nulliparous at diagnosis and reporting treatment-related ovarian damage were both strongly associated with higher reproductive concerns and with depressive symptoms.
Reported reproductive concerns after breast cancer treatment were a significant contributor to consistent depressive symptoms. Younger survivors would benefit from additional information and support related to reproductive issues.
breast cancer; young; depression; fertility; reproduction
The safety of pregnancy after breast cancer is an important issue for many younger breast cancer survivors and their health care providers. Current research does not indicate that pregnancy negatively affects survival, but the “healthy mother bias,” suggesting that survivors who go on to become pregnant are a self-selected healthier group based on their prognosis, has led to cautious interpretation of these findings. No studies have systematically evaluated the potential for this bias.
This nested case-control study includes 81 younger participants from the Women’s Healthy Eating and Living Study (WHEL) (N=3088). Our sample includes 27 cases who had children after breast cancer and 54 controls, matched on age and stage at diagnosis. We used hierarchical linear modeling to accommodate longitudinal data with individuals nested within matched sets (cases and controls). The primary aim was to evaluate the association between summary scores of health and childbearing after breast cancer. Covariates were added for adjustment and to improve model precision.
Controlling for other variables in the model, physical health scores were not different between cases and controls (B=0.14, p=0.96). Mental health scores were marginally higher among cases (B=6.40, p=0.08), as compared to controls, a difference considered clinically significant.
This preliminary study did not find evidence of a healthy mother bias based on physical health. However, mental health was 6 points higher (p=0.08) among those who had children, indicating that the role of mental health needs evaluation in future research. Larger studies are needed to verify these findings.
The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.7%). About 60% of breast tumors were estrogen receptor (ER)+/progesterone receptor (PR)+; 21% were ER−/PR−. Among 8,118 participants with information on HER-2 tumor status, 74.8% were HER-2− and 18.5% were HER-2+. At 1–2 years post-diagnosis (on average) 17.9% of participants were obese (BMI ≥30 kg/m2), 32.6% were overweight (BMI 25–29 kg/m2) and 59.9% met the 2008 Physical Activity Guidelines for Americans (≥ 2.5 hours per week of moderate activity). During follow-up (mean=8.4 years), 3,736 deaths (2,614 from breast cancer), and 3,564 recurrences have been documented. After accounting for differences in year of diagnosis and timing of post-diagnosis enrollment, five-year overall survival estimates were similar across cohorts. This pooling project of 18,000 breast cancer survivors enables the evaluation of associations of post-diagnosis lifestyle factors, QOL, and breast cancer outcomes with an adequate sample size for investigation of heterogeneity by hormone-receptor status and other clinical predictors. The project sets the stage for international collaborations for the investigation of modifiable predictors for breast cancer outcomes.
Breast neoplasm; Survival; Recurrence; Life style
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.
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.
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.
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.
breast cancer; diet; ethnicity; race; randomized controlled trial; survival
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.
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.
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.
These results appear to support testing an intervention to improve physical health in breast cancer patients among patients after the acute stage of treatment.
breast cancer; physical health; survival; mortality
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.
breast neoplasms; proportional hazards models; survival
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.
Cancers; CYP; Epidemiology; Pharmacogenetics; Genotype
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.
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.
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.
The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone.
Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence.
Postmenopausal; hot flashes; sex hormones; breast cancer
During the 1990s, both prevalence and average cigarette consumption declined in the United States, but age-specific changes have not been reported.
All four of the nationally and state representative U.S. Current Population Surveys—Tobacco Use Supplements from 1991–2002 (n = 542,470) were analyzed for trends in cigarette consumption among smokers in three age groups: 18–29, 30–44, and 45–64 years. A strength of tobacco control index ranking state of residence was added and weighted logistic regression analyses undertaken.
Over the decade, both prevalence and average consumption declined. Moderate-heavy smoking (≥15 cigarettes/day [CPD]) prevalence fell strongly over the period in all three age groups. For those aged ≥30 years, this reduction was accompanied by a similar drop in total smoking prevalence. For those aged 18–29 years, this reduction was associated with an increase in very light smoking (<5 CPD; 12% daily and 88% intermittent smokers) to 22.5% of current smokers with a much smaller reduction in prevalence. Smoke-free homes more than doubled in each age group and mediated the increase in very light smoking levels. Smoke-free workplaces and the strength of tobacco control in the state were also important predictors. Very light smoking was particularly prevalent among college students and graduates.
The marked reduction in prevalence of moderate-heavy smoking across age groups should translate into a reduced population risk of smoking-related disease in the near term. That this reduction is offset by an increase in light and intermittent smoking in young adults suggests the effectiveness of tobacco industry marketing and needs further research.
Purpose of Review
To clarify the role of dietary pattern on prognosis in breast cancer survivors.
Observational trials show mixed results that do not strongly support an independent role for dietary pattern in prognosis. WINS and WHEL are two large randomized controlled trials that address this question. The Interventions from both studies achieved significant reductions in energy from fat and the WHEL Study achieved large increases in vegetables, fruit, and fiber. WINS examined postmenopausal women only and reported a not-quite-significant improved prognosis for women in the intervention group, with the benefit focused on ipsilateral localized recurrences but little improvement in the most important distal recurrences. This review considers only WHEL postmenopausal women to aid a direct comparison with WINS. The WHEL Study reported a convincing lack of association between diet and prognosis. However, a secondary analysis suggests that the dietary intervention reduced distal recurrences among the sub-group without hot flashes at baseline.
There is no convincing evidence that changing dietary pattern following breast cancer diagnosis will improve prognosis for most women with early stage breast cancer. However, it would appear to be important for some sub-groups. Further investigation of mechanisms for such selective action is needed.
breast cancer prognosis; dietary pattern; randomized trials
The utilization of archived, formalin-fixed paraffin-embedded (FFPE) tumor samples for massive parallel sequencing has been challenging due to DNA damage and contamination with normal stroma. Here, we perform whole genome sequencing of DNA isolated from two triple-negative breast cancer tumors archived for >11 years as 5 µm FFPE sections and matched germline DNA. The tumor samples show differing amounts of FFPE damaged DNA sequencing reads revealed as relatively high alignment mismatch rates enriched for C·G > T·A substitutions compared to germline samples. This increase in mismatch rate is observable with as few as one million reads, allowing for an upfront evaluation of the sample integrity before whole genome sequencing. By applying innovative quality filters incorporating global nucleotide mismatch rates and local mismatch rates, we present a method to identify high-confidence somatic mutations even in the presence of FFPE induced DNA damage. This results in a breast cancer mutational profile consistent with previous studies and revealing potentially important functional mutations. Our study demonstrates the feasibility of performing genome-wide deep sequencing analysis of FFPE archived tumors of limited sample size such as residual cancer after treatment or metastatic biopsies.
To compare trends in African‐American (AA) and non‐Hispanic white (NHW) smoking between states categorised as having three different levels of tobacco control practice in the 1990s.
Setting and participants
Analysis of 1992–3 to 2001–2 Tobacco Use Supplements to the Current Population Survey for differences in adult (20–64 years) daily smoking prevalence for AAs and NHWs across states: California (CA; high cigarette price/comprehensive programme), New York (NY) and New Jersey (NJ; high cigarette price/no comprehensive programme), and tobacco growing states (TGS; low cigarette price/no comprehensive programme).
From 1992–3 to 2001–2, there were large declines in AA smoking across states (2.7–3.8% decrease/year, adjusted for age, income, education, gender; p<0.05). Adjusted NHW smoking prevalence declined significantly only in CA. AA prevalence declined significantly and did not differ across state groups. In all years, in all state groups, adjusted prevalence was either not significantly different or was lower for AAs than for NHWs. More recent cohorts of AAs appeared to have taken up smoking at lower rates than older cohorts.
There were uniformly large declines in AA smoking from 1992–3 to 2001–2 across states, independent of type of tobacco control strategy. Further research is needed into factors associated with smoking declines among AAs.