Women's Healthy Eating And Living Research Articles

Living Alone, Physical Health, and Mortality in Breast Cancer Survivors: A Prospective Observational Cohort Study.

Living alone, particularly for individuals with poor physical health, can increase the likelihood of mortality. This study aimed to explore the individual and joint associations of living alone and physical health with overall mortality among breast cancer survivors in the Women's Healthy Eating and Living (WHEL). We collected baseline, 12-month and 48-month data among 2869 women enrolled in the WHEL cohort. Living alone was assessed as a binary variable (Yes, No), while scores of physical health were measured using the RAND Short Form-36 survey (SF-36), which include four domains (physical function, role limitation, bodily pain, and general health perceptions) and an overall summary score of physical health. Cox proportional hazard models were used to evaluate associations. No significant association between living alone and mortality was observed. However, several physical health measures showed significant associations with mortality (p-values < 0.05). For physical function, the multivariable model showed a hazard ratio (HR) of 2.1 (95% CI = 1.02-4.23). Furthermore, the study examined the joint impact of living alone and physical health measures on overall mortality. Among women with better physical function, those living alone had a 3.6-fold higher risk of death (95% CI = 1.01-12.89) compared to those not living alone. Similar trends were observed for pain. However, regarding role limitation, the pattern differed. Breast cancer survivors living alone with worse role limitations had the highest mortality compared to those not living alone but with better role limitations (HR = 2.6, 95% CI = 1.11-5.95). Similar trends were observed for general health perceptions. Our findings highlight that living alone amplifies the risk of mortality among breast cancer survivors within specific health groups.

Abstract PD12-09: PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis

Abstract Background: Tumor characteristics such as grade, stage and receptor status are associated with breast cancer (BC) prognosis. Less is known about modifiable factors and BC prognosis. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism, generated in conditions of increased oxidative stress. AGEs irreversibly accumulate in our tissues over time with pathogenic effects on genetic fidelity, protein function, cell signaling pathways, and chronic inflammatory diseases. The total body AGE pool is composed of endogenous AGEs and exogenous AGEs (consumed mainly through processed foods and those cooked at high temperatures). Serum AGE (sAGE) levels, a reflection of total body AGE, are higher in people with poor diet quality, lower levels of physical activity, and in women with BC compared to healthy controls. AGEs promote growth, migration and invasion in BC cell lines and activate prognostic inflammatory mediators such as interleukin-6 and C-reactive protein. Dietary AGEs have been associated with increased BC risk and increased mortality after BC diagnosis whereas lifestyle interventions can lower dietary and sAGE levels. The impact of sAGE levels, a better estimate of total body AGE than dietary AGE, on BC prognosis has not been previously evaluated. Methods: The Women’s Healthy Eating and Living (WHEL) study randomized 3088 BC patients stage I-III who completed their primary therapy to a high-vegetable, low-fat diet or control and followed for a median of 7.3 years. Main outcomes were invasive BC events (recurrence or new primary N=518), death due to BC (N=262) and deaths from any cause (N=315). sAGE was measured as the AGE metabolite carboxymethyllysine (ug/ml) from WHEL fasting blood specimens at study entry. sAGE was logged and corrected for plate batch effect via linear regression and analyzed in continuous scale and in quintiles. The Kaplan-Meier method and Cox regression model were performed for risk impact of sAGE on overall survival (OS), recurrence free survival (RFS), breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). We additionally adjusted in Cox models for potential confounding variables (age, race, BMI, smoking, alcohol use, physical activity, tumor characteristics). Results: 2564 participants had sAGE available. After excluding samples for excessive variabilities, 2315 samples were analyzed. Raw corrected sAGE ranged from 0.0-48.15 ug/ml (median 7.39); logged and corrected range -5.04-1.67. sAGE was positively associated with BMI (p&amp;lt;.0001, rs 0.10) and negatively associated with physical activity (p&amp;lt; .001, rs.-0.06). sAGE was not significantly associated with tumor stage, grade, receptor status, or race or menopausal status. Comparing the highest quintile (logged and corrected range=0.33~1.67) to the lowest quintile (range=-5.04~-0.30), sAGE was significantly associated with all survival outcomes (Table 1). As a continuous variable, AGE was associated with worse OS (HR 1.38, P=.031, β .32) and RFS (HR 1.29, P=.028, β .25) with a trend towards worse DMFS (HR 1.28, P=.067, β .25) and BCSS (HR 1.36, P=.06, β .31). Conclusions: Higher sAGEs are associated with worse survival outcomes in BC and may represent a novel, lifestyle-linked, modifiable prognostic biomarker in BC. Interventions aimed at lowering sAGE levels should be tested for their impact on known prognostic biomarkers as well as clinical outcomes. Individualized cancer-specific lifestyle recommendations are a crucial but currently lacking component of personalized cancer medicine. Citation Format: Lindsay L. Peterson, Yu Tao, Jingqin Luo, Graham A. Colditz, Yikyung Park, Jennifer A. Ligibel, David Turner. PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-09.

Interrelationship of Seasons With Inflammation, Foods, Cardio-Metabolic Health, and Smoking Status Among Breast Cancer Survivors

Abstract Objectives Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. Methods We conducted a cross-sectional study by leveraging a large cohort, the Women's Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. Results In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years 15, in whom we observed no benefit of red meat intakes in winter. Conclusions Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat. Funding Sources TRDRP.

Computational Treatment Simulations to Assess the Need for Personalized Tamoxifen Dosing in Breast Cancer Patients of Different Biogeographical Groups.

Simple SummaryTamoxifen is a drug often used to treat the most common type of breast cancer. Its metabolite endoxifen is formed by the liver enzyme CYP2D6, whose activity is variable and depends on a patient’s genetic profile. The frequency of CYP2D6 variants with different functional enzymatic activity varies largely between populations. To ensure sufficient efficacy of tamoxifen, a certain target concentration of endoxifen is needed, and 20% of White breast cancer patients have been shown not to reach this target concentration. However, little is known about the risk of not attaining the endoxifen target amongst other ethnic populations. This study investigated the risk for suboptimal endoxifen concentration in nine different biogeographical populations based on their distinct CYP2D6 genetic profile. The variability between the populations was high (up to three-fold), and East Asian breast cancer patients were identified as the population with the highest need for personalized tamoxifen dosing.Tamoxifen is used worldwide to treat estrogen receptor-positive breast cancer. It is extensively metabolized, and minimum steady-state concentrations of its metabolite endoxifen (CSS,min ENDX) >5.97 ng/mL have been associated with favorable outcome. Endoxifen formation is mediated by the enzyme CYP2D6, and impaired CYP2D6 function has been associated with lower CSS,min ENDX. In the Women’s Healthy Eating and Living (WHEL) study proposing the target concentration, 20% of patients showed subtarget CSS,min ENDX at tamoxifen standard dosing. CYP2D6 allele frequencies vary largely between populations, and as 87% of the patients in the WHEL study were White, little is known about the risk for subtarget CSS,min ENDX in other populations. Applying pharmacokinetic simulations, this study investigated the risk for subtarget CSS,min ENDX at tamoxifen standard dosing and the need for dose individualization in nine different biogeographical groups with distinct CYP2D6 allele frequencies. The high variability in CYP2D6 allele frequencies amongst the biogeographical groups resulted in an up to three-fold difference in the percentages of patients with subtarget CSS,min ENDX. Based on their CYP2D6 allele frequencies, East Asian breast cancer patients were identified as the population for which personalized, model-informed precision dosing would be most beneficial (28% of patients with subtarget CSS,min ENDX).

Interrelationship of Seasons with Inflammation, Red Meat, Fruit, and Vegetable Intakes, Cardio-Metabolic Health, and Smoking Status among Breast Cancer Survivors.

Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. We conducted a cross-sectional study by leveraging a large cohort, the Women’s Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years ≥ 15, in whom we observed no benefit of red meat intakes in winter. Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat.

Dietary Acid Load, Smoking Intensity and Total Mortality

Abstract Objectives Former smokers comprise 30–40% among breast cancer survivors. Smoking can cause many biological damages which can still exist in past smokers and make them more susceptible to certain dietary and environmental challenges. Past smokers may have accelerated aging process than never smokers. Limited studies have examined the impacts of dietary acid load total mortality among breast cancer survivors who are never or former smokers. Methods We leveraged an existing cohort, the Women's Healthy Eating and Living (WHEL) Study, which enrolled 3088 women with early stage breast cancer at baseline. This cohort collected dietary information through 24-hour recalls at years 0, 1, and 4, which enabled us to measure dietary acid load accurately and longitudinally. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score, and net endogenous acid production (NEAP) score. This cohort also assessed past smoking history by pack-years which allowed us to carefully and accurately past smoking intensity. Results In this study, we found that dietary acid load itself was not significantly associated with total mortality among never smokers but significantly associated with total mortality among past smokers who had pack-years &amp;gt;0. When we evaluated the joint impact of dietary acid load and pack-years, women with dietary acid load above median and pack-years ≥15 had 2.38 (95% CI 1.58–3.59) times of risk of total mortality as compared to the reference group (women with dietary acid load below median and pack-years = 0). Conclusions Results from our study will be important for patient care and aid in creating tailored precision nutrition recommendation for breast cancer survivors who are former smoker. Funding Sources University internal funds, NIH/NCI.

MiRNAs and Long-term Breast Cancer Survival: Evidence from the WHEL Study

There is substantial variation in breast cancer survival rates, even among patients with similar clinical and genomic profiles. New biomarkers are needed to improve risk stratification and inform treatment options. Our aim was to identify novel miRNAs associated with breast cancer survival and quantify their prognostic value after adjusting for established clinical factors and genomic markers. Using the Women's Healthy Eating and Living (WHEL) breast cancer cohort with >15 years of follow-up and archived tumor specimens, we assayed PAM50 mRNAs and 25 miRNAs using the Nanostring nCounter platform. We obtained high-quality reads on 1,253 samples (75% of available specimens) and used an existing research-use algorithm to ascertain PAM50 subtypes and risk scores (ROR-PT). We identified miRNAs significantly associated with breast cancer outcomes and then tested these in independent TCGA samples. miRNAs that were also prognostic in TCGA samples were further evaluated in multiple regression Cox models. We also used penalized regression for unbiased discovery. Two miRNAs, 210 and 29c, were associated with breast cancer outcomes in the WHEL and TCGA studies and further improved risk stratification within PAM50 risk groups: 10-year survival was 62% in the node-negative high miR-210-high ROR-PT group versus 75% in the low miR-210- high ROR-PT group. Similar results were obtained for miR-29c. We identified three additional miRNAs, 187-3p, 143-3p, and 205-5p, via penalized regression. Our findings suggest that miRNAs might be prognostic for long-term breast cancer survival and might improve risk stratification. Further research to incorporate miRNAs into existing clinicogenomic signatures is needed.

Associations between Dietary Acid Load and Biomarkers of Inflammation and Hyperglycemia in Breast Cancer Survivors.

Metabolic acidosis can lead to inflammation, tissue damage, and cancer metastasis. Dietary acid load contributes to metabolic acidosis if endogenous acid–base balance is not properly regulated. Breast cancer survivors have reduced capacities to adjust their acid–base balance; yet, the associations between dietary acid load and inflammation and hyperglycemia have not been examined among them. We analyzed data collected from 3042 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) Study who had provided detailed dietary intakes and measurements of plasma C-reactive protein (CRP) and hemoglobin A1c (HbA1c). Using a cross-sectional design, we found positive associations between dietary acid load and plasma CRP and HbA1c. In the multivariable-adjusted models, compared to women with the lowest quartile, the intakes of dietary acid load among women with the highest quartile showed 30–33% increases of CRP and 6–9% increases of HbA1c. Our study is the first to demonstrate positive associations between dietary acid load and CRP and HbA1c in breast cancer survivors. Our study identifies a novel dietary factor that may lead to inflammation and hyperglycemia, both of which are strong risk factors for breast cancer recurrence and comorbidities.

Dietary Acid Load in Relation to Inflammation and Glycemic Status in Women with Breast Cancer (P18-095-19)

ObjectivesTo determine the associations between dietary acid load and serum C-reactive protein (CRP) and hemoglobin A1c (HbA1c) among breast cancer survivors. We hypothesized that high dietary acid load is positively associated with CRP and HbA1c. MethodsUsing a cross-sectional design, we analyzed data collected from 3088 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) Study who had provided detailed four randomly selected self-reported 24-hr dietary recalls over a three-week period followed by a blood sample that was used to validate the dietary self reports and measure of plasma CRP and HbA1c from washed red blood cells. Two commonly used dietary acid load scores were created, namely the potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. The PRAL score takes into account the intestinal absorption rates for contributing nutrient ionic balances for protein, potassium, calcium and magnesium and the dissociation of phosphate at pH 7.4. The NEAP score uses total protein and potassium intake as the main components involved in acid production. ResultsPRAL and NEAP were both positively associated with plasma CRP and HbA1c. In multivariable adjusted models, compared to women in the lowest quartile, those in the highest quartile of PRAL and NEAP had 32% and 31% increases in CRP, respectively and 9% and 6% increases in HbA1c, respectively after adjustment for total calorie intakes, age, body mass index, breast cancer stage, hormone receptor status, and type of chemotherapy. ConclusionsThis is the first demonstration that dietary acid load is associated with CRP and HbA1c in breast cancer patients. Our study identifies a novel dietary factor that may lead to inflammation and hyperglycemia, both of which are strong risk factors for breast cancer recurrence and other comorbidities. Funding SourcesSDSU start-up funds.

Red Meat and Inflammation and A1c in Breast Cancer Women (P05-038-19)

ObjectivesTo determine the associations of processed and unprocessed red meat with serum C-reactive protein (CRP) and hemoblobin A1c (HbA1c) among breast cancer survivors. We hypothesized that processed and unprocessed red meat can increase CRP and HbA1c.These associations will not be completely mediated by body mass index (BMI). MethodsUsing a cross-sectional design, we analyzed data collected from 3088 breast cancer survivors who enrolled in the Women’s Healthy Eating and Living (WHEL) Study and had provided four detailed 24-hour dietary recalls over a 3-week period along with a blood sample to validate dietary pattern and measure plasma CRP and HbA1c from washed red blood cells. Intakes of processed and unprocessed red meat were extracted from dietary recalls. CRP concentrations were measured using high-sensitivity electrochemiluminescence assay. HbA1C was measured using ion exchange high-performance liquid chromatography. ResultsWe found significant positive associations for both unprocessed and processed red meat with plasma CRP and HbA1c. In multivariable adjusted models, compared to women with the lowest quintile intakes of unprocessed red meat, women with highest quintile had a 19% increase of CRP and had an 11% increase of HbA1c after adjustment for BMI. Further adjustment for total vegetable intake did not materially change these associations. We observed similar patterns for processed red meat. The magnitudes of the associations of processed red meat with CRP and HbA1c were similar to that of unprocessed meat with CRP and HbA1c after adjustment of BMI. P-values for trends were less than 0.002 for all of these associations. ConclusionsCRP and HbA1c are strong predictors for breast cancer prognosis and development of comorbidities (e.g., diabetes). Although many studies examined the association of red meat with CRP and HbA1c in general healthy population, few studies were conducted among breast cancer survivors. Our results for the first time demonstrate that the positive associations between unprocessed and processed red meat consumption and inflammation and hyperglycemia are not fully mediated by BMI among breast cancer women. Funding SourcesSDSU start-up funds.

Body mass index and persistent pain after breast cancer surgery: findings from the women's healthy eating and living study and a meta-analysis.

The purpose of this study is to evaluate the association between body mass index (BMI) and persistent pain after breast cancer surgery in a prospective study and synthesize available evidence through a meta-analysis. In the Women's Healthy Eating and Living (WHEL) Study, 3,088 women diagnosed of breast cancer were enrolled and assessed. After 4 years, a subgroup of 2,131 women was re-assessed for the pain information. Logistic regression models were used to assess the associations of baseline BMI and BMI change between baseline and 4 years of follow-up with general pain symptoms at 4 years of follow-up. We further synthesized all available evidence from observational studies by searching PubMed and Embase up to February 2017. In the WHEL study, baseline BMI was linearly associated with an increased risk of persistent pain at 4 years of follow-up (odds ratio (OR) (95% confidence interval (CI)): 1.07 (1.05-1.10)). After adjusting for baseline BMI, BMI change since baseline was associated with persistent pain (OR (95% CI) for every unit increase: 1.10 (1.04-1.16)). After searching the literature, additional eight studies were eligible to be included in the meta-analysis. After pooling estimates from all nine studies, there was a positive association with persistent pain development comparing obesity or overweight with normal weight. Available data suggested a linear relationship between BMI and persistent pain (OR (95% CI) for every one unit increment of BMI: 1.04 (1.02-1.07)). Overall, our analyses suggested that BMI might be positively associated with risk of persistent pain after breast cancer surgery.

Medical synopsis: Nightly fasting may assist breast cancer patients and other people with cancer

DesignA multi-site randomised clinical trial. ParticipantsThe Women's Healthy Eating and Living (WHEL) study of patients with breast cancer. Data was collected from 2413 women with breast cancer but without diabetes mellitus, aged 27–70 years at diagnosis. A total of 2064 participants (85.5%) were Caucasian with 1335 (55.3%) college educated. InterventionDietary analysis including timing of consumption at baseline, year 1 and year 4.A 24-h dietary recall collected by telephone on random days during a 3-week period, stratified for weekends vs weekdays.Nightly fasting duration was estimated by calculating the elapsed hours between the first and last eating episode for each day and subtracting that time from 24h.Potential confounders were identified including daily intake (kilocalories), eating episodes per day and eating after 8pm. ComparatorNo comparator was used in this study. Major outcomesParticipants reported a mean (SD) nightly fasting duration of 12.5h and 4.4 eating episodes per day.One-third of the sample consumed 25kcal or more after 8pm.A short nightly fasting duration (<13h per night) was significantly associated with college education, a lower BMI, shorter sleep duration, higher self-reported kilocalorie intake, more eating episodes, and eating after 8pm.A short nightly fast (<13h) was significantly associated with an increased risk for breast cancer recurrence (36% higher risk).Each 2-h increase in nightly fasting duration was statistically significant for lower HbA1c level (0.37mmol/mol lower) and more hours of sleep per night.Nightly fasting was not associated with BMI or CRP concentrations.Eating after 8pm was significantly associated with increased higher CRP and BMI. SettingsThe United States of America: Clinical sites included University of California, San Diego; University of California, Davis; Stanford University; Kaiser Permanente, Northern California; M.D. Anderson Cancer Centre; Arizona Cancer Centre; and Kaiser Permanente Center for Health Research. ConclusionProlonged nightly fasting duration (13h or more), may be a simple, non-pharmacologic strategy for reducing the risk of breast cancer recurrence. In addition, improvements in gluco-regulation and sleep may be mechanisms of action linked with nightly fasting and breast cancer prognosis.

Abstract P3-09-01: Intermittent fasting in breast cancer risk and survivorship: Insight from the women's healthy eating and living study

Abstract Intermittent fasting (IF) regimens have gained widespread attention in recent years for their possible role in human health and disease risk. In mice, IF schedules that are aligned with sleep-wake cycles appear to positively influence metabolic processes related to cancer risk and may have direct effects on carcinogenesis; however the impact of these regimens on cancer risk in humans remain unclear. We examined associations between nighttime fasting duration (a form of IF aligned with sleep-wake cycles) and (1) biomarkers demonstrated to be associated with breast cancer prognosis; and (2) long-term clinical outcomes in a sample of breast cancer survivors from the Women's Healthy Eating and Living (WHEL) Study. Dietary data were available for 3,061 non-diabetic women enrolled in the WHEL Study. Nighttime fasting duration was calculated using time-stamped 24-hour dietary recalls collected at the baseline, Year 1, and Year 4 study assessment periods. Approximately 3-4 dietary records were collected per subject at each assessment period, and these records were averaged to yield a single estimate of nighttime fasting duration per time point. Glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP) levels were ascertained from blood specimen collected at baseline. Clinical outcomes recorded during the study follow-up include breast cancer events (recurrence or new primary) and mortality. Linear regression models examined the associations of nighttime fasting with baseline concentrations of HbA1c and CRP. Delayed-entry Cox proportional hazard models were used to assess the association between nighttime fasting duration, recorded at the baseline, Year 1, and Year 4 assessments, with clinical outcomes. These models used a counting process method to account for repeated measures. All models controlled for basic demographic factors, participant characteristics (BMI, comorbidity status, sleep duration), breast cancer characteristics (stage, grade, anti-estrogen use), and dietary variables (total calories, evening calories, eating frequency). Women fasted an average of 12.5 hours per night (SD=1.6 hours). There were 520 new breast cancer events, and 569 deaths during study follow up. HbA1c level was significantly and inversely related to nighttime fasting duration. Each 2-hour increase in the nighttime fasting duration was associated with a 0.2-unit decrease in HbA1c (β=-0.21; p=0.03 with HbA1c expressed as mmol/mol), and there was no evidence of mediation or effect modification by participant characteristics, e.g., BMI. No associations were observed between nighttime fasting duration and CRP. In longitudinal models, women who fasted less than 13.1 hours per night (bottom two tertiles of nightly fasting distribution) had roughly a 50% higher hazard for experiencing a breast cancer event, compared to women who fasted at least 13.1 hours per night (HR: 1.46; 95%CI: 1.11-1.93; p&amp;lt;0.01). Nighttime fasting duration was not associated with mortality. Findings suggest that increasing the length of the nighttime fasting interval could be a simple, feasible, and novel strategy to improve glucose control and reduce breast cancer risk. Randomized trials confirming the link between nighttime fasting duration and breast cancer risk are warranted. Citation Format: Marinac CR, Neslon SH, Natarajan L, Sears DD, Breen CI, Pierce JP, Patterson RE. Intermittent fasting in breast cancer risk and survivorship: Insight from the women's healthy eating and living study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-09-01.

Abstract PD4-08: Post-diagnosis physical activity and comorbidities, not BMI, explain mortality risk in the after breast cancer pooling project

Abstract Background: In its 2014 position statement, ASCO concluded that obesity is associated with worse prognosis after cancer diagnosis. However in the same year, a comprehensive review by the World Cancer Research Fund concluded that there was limited evidence that greater body fatness increases risk of overall or breast cancer mortality, indicating that further investigation into lifestyle factors are needed. The After Breast Cancer (ABC) Pooling Project has reported, separately, significant mortality effects of pre-diagnosis BMI and of post-diagnosis physical activity (PA). We investigate whether the effect of BMI can be limited to subgroups characterized by comorbidities and physical activity. Methods: Data are from the three US cohorts that were harmonized in the ABCPP (n=9513) including: the Women's Healthy Eating and Living (WHEL), Life After Cancer Epidemiology (LACE), and Nurses' Health (NHS) studies. Stepwise delayed entry Cox proportional hazards models examined each lifestyle predictor (BMI, PA, and comorbidities assessed after diagnosis) sequentially and together in multivariate models for breast cancer and all-cause mortality. Results: In multivariate models without the other two target variables, PA was significantly associated with a 17% decrease in the risk of breast cancer mortality among women in the highest quartile of PA (MET hr/wk &amp;gt; 21.4), compared to the lowest quartile (MET hr/wk &amp;lt; 2.7) (HR=0.81,95% CI= 0.67,0.97). In the model with major comorbidities, there was a significant 40% increase in the risk of breast cancer mortality among women diagnosed with both diabetes and hypertension (HR=1.40, 95% CI= 1.01,1.93). In the model with BMI, there was no significant association with risk of breast cancer mortality. These results were essentially unchanged with all variables in a single model. For all-cause mortality, the PA-only model showed a significant PA effect with the hazard decreasing from 20% to 40% across quartiles (Q2 HR=0.80, 95% CI=0.71,0.90, Q4 HR=0.62, 95% CI=0.54,0.71). In the comorbidity-only model, both diabetes and hypertension significantly increased hazard of all-cause mortality 80% and 33%, respectively. Having both diagnoses was associated with a significant, 2.3 fold increase in all-cause mortality (HR=2.34, 95% CI= 1.95,2.81). In the BMI-only model, being underweight was associated with a significant 2.4 fold increase in risk of all-cause mortality, and there was a 20 and 37% increase in risk associated with being categorized as obese I or II (Obese I HR=1.23, 95% CI=1.07,1.40, Obese II HR=1.37, 95% CI=1.16,1.61). With all three variables in the model, the risk associated with being obese decreased and became non-significant (Obese I HR=1.06, Obese II HR=1.05), while the significance, strength, and direction of the association of comorbidities and PA with all-cause mortality remained constant. Conclusion: These data suggest that post-diagnosis comorbidities and lack of physical activity, rather than high BMI , are the important risk factors for all-cause and breast cancer specific mortality. While needing further validation, these suggest that physical activity interventions and monitoring treatment for comorbidities should become standard of care for breast cancer survivors. Citation Format: Nelson SH, Marinac CR, Patterson RE, Nachuta SJ, Caan BJ, Chen WY, Shu X-O, Pierce JP. Post-diagnosis physical activity and comorbidities, not BMI, explain mortality risk in the after breast cancer pooling project. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-08.

Baseline Depressive Symptoms, Completion of Study Assessments, and Behavior Change in a Long-Term Dietary Intervention Among Breast Cancer Survivors

BackgroundDepressive symptoms can lower adherence and change in dietary studies. Behavioral activation may reduce these effects.PurposeThis study aims to assess relationships among depressive symptoms on adherence and dietary change in the Women’s Healthy Eating and Living (WHEL) StudyMethodsSecondary analyses from the WHEL Study, which achieved major dietary change in breast cancer survivors (N = 2817), were conducted. Logistic regressions were undertaken of baseline depressive symptoms (six-item Center for Epidemiologic Studies Depression Scale (CES-D)) with (1) completion of 1- and 4-year study assessments and (2) validated change in dietary behavior in the intervention group.ResultsIn the comparison group (vs. intervention), depressive symptoms lowered completion of dietary recalls and clinic visits [4 years: odds ratio (OR) = 2.0; 95 % confidence interval (CI) = 1.4–3.0]. The behaviorally oriented intervention achieved major change in those furthest from study targets, although changes were lower in those with depressive symptoms: fruit/vegetable (+37.2 %), fiber (+49.0 %), and fat (−22.4 %).ConclusionsBehavioral activation in dietary change interventions can overcome the impact of depressive symptoms.

To Your Health: How Does the Latest Research on Alcohol and Breast Cancer Inform Clinical Practice?

To Your Health: How Does the Latest Research on Alcohol and Breast Cancer Inform Clinical Practice?

Impact of Healthy Eating Practices and Physical Activity on Quality of Life among Breast Cancer survivors

Following breast cancer diagnosis, women often attempt to modify their lifestyles to improve their health and prevent recurrence. These behavioral changes typically involve diet and physical activity modification. The aim of this study was to determine association between healthy eating habits and physical activity with quality of life among Iranian breast cancer survivors. A total of 100 Iranian women, aged between 32 to 61 years were recruited to participate in this cross-sectional study. Eating practices were evaluated by a validated questionnaire modified from the Women's Healthy Eating and Living (WHEL) study. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). A standardized questionnaire by the European Organization of Research and Treatment of Cancer Quality of Life and its breast cancer module (EORTC QLQ-C30/+BR-23) were applied to determine quality of life. Approximately 29% of the cancer survivors were categorized as having healthy eating practices, 34% had moderate eating practices and 37% had poor eating practices based on nutrition guidelines. The study found positive changes in the decreased intake of fast foods (90%), red meat (70%) and increased intake of fruits (85%) and vegetables (78%). Generally, breast cancer survivors with healthy eating practices had better global quality of life, social, emotional, cognitive and role functions. Result showed that only 12 women (12%) met the criteria for regular vigorous exercise, 22% had regular moderate-intensity exercise while the majority (65%) had low-intensity physical activity. Breast cancer survivors with higher level of physical activity had better emotional and cognitive functions. Healthy eating practices and physical activity can improve quality of life of cancer survivors. Health care professionals should promote good dietary habits and physical activity to improve survivors' health and quality of life.

Risk factors associated with breast cancer-related lymphedema in the WHEL Study

Lymphedema is a significant health problem faced by a large percentage of breast cancer survivors. The Women's Healthy Eating and Living (WHEL) Study has a unique dataset collected after the completion of breast cancer treatment, which allowed a focused analysis of risk factors for breast cancer-related lymphedema. Participant characteristics, treatment modalities, and health behaviors were examined as potential predictors of lymphedema among breast cancer survivors with univariate analyses and multivariate logistic regression. Lymphedema status was assessed for 83 % of the study cohort (2,431 of the 2,917 WHEL participants). Among these respondents, 692 (28.5 %) women reported yes to either a physician's diagnosis of lymphedema or a question on arm/hand swelling. When compared to other participants, women with lymphedema were diagnosed at a younger age, more likely to have a higher body mass index, had a larger tumor size, had more lymph nodes removed, more likely to have a mastectomy with radiation therapy, and more likely to have chemotherapy. In the final multivariate-adjusted model, body mass index greater than 25 kg/m(2) (p < 0.01), the removal of 11 or more lymph nodes (p < 0.01), and breast cancer surgery plus radiation therapy (p < 0.01) showed a strong independent association with developing breast cancer-related lymphedema. The results of this study highlight the importance of educating breast cancer survivors about the modifiable risk factors (e.g., body mass index) associated with the development of lymphedema. Breast cancer survivors at risk for lymphedema may benefit from interventions aimed at achieving or maintaining a healthy body weight.

NEW and RENEW: Building the Case for Weight Loss in Breast Cancer

Obesity has been linked to poor outcomes in women with early breast cancer. A meta-analysis of 43 studies examining the relationship between weight at the time of breast cancer diagnosis and prognosis in women with early-stage breast cancer demonstrated a 33% increase in the risk of breast cancer–related and overall mortality in obese versus nonobese women. Observational studies have also shown that physical activity, an important mediator of weight maintenance, is associated with better survival in women with early-stage breast cancer. Finally, two large-scale randomized trials testing the impact of dietary modification on cancer outcomes in breast cancer survivors have provided indirect evidence that weight loss after diagnosis could lead to lower rates of recurrence. The WINS (Women’s Interventional Nutrition Study) trial reported a 24% reduction in the risk of recurrence in breast cancer survivors randomly assigned to a low-fat diet group, who decreased dietary fat to 20% of calories and lost an average of 6 lbs, as compared with controls. In contrast, the WHEL (Women’s Healthy Eating and Living) study did not demonstrate a lower risk of recurrence in breast cancer survivors randomly assigned to a low-fat, high fruit and vegetable dietary intervention. Intervention participants in this study did not experience weight loss, and although there were a number of other differences between the studies, the weight change in WINS has been suggested as one potential reason for the difference in the outcomes of the two studies. Despite strong observational evidence that weight and related factors could influence cancer outcomes, there are no data from randomized trials testing the impact of purposeful weight loss after breast cancer diagnosis on the risk of cancer recurrence and mortality. A number of small and moderate-sized weight loss and physical activity intervention studies in breast cancer populations have demonstrated the feasibility of lifestyle change and documented additional beneficial effects on quality of life, fitness, and fatigue. To optimally design more definitive studies, interventions that reliably, cost effectively, and durably change lifestyle behaviors in large groups of breast cancer survivors are needed. Enhanced understanding of the impact of lifestyle change on biologic factors implicated in the lifestylecancer association will guide study design and strengthen the scientific rationale for such studies. Two reports in Journal of Clinical Oncology (JCO) provide crucial information for the development of large-scale trials testing the impact of lifestyle change on disease outcomes in patients with cancer. In the first report, Demark-Wahnefried et al demonstrate the efficacy of a telephone-based lifestyle intervention in effecting long-lasting changes in diet, physical activity, and weight in 641 survivors of colon, prostate, and breast cancers, providing feasibility data for large-scale, distance-based lifestyle interventions among cancer survivors. In the second report, Campbell et al describe the impact of different types of lifestyle interventions on biomarkers linked to breast cancer risk and prognosis in postmenopausal women, providing some of the first data comparing the effect of physical activity and weight loss, with or without a physical activity component, on putative pathways linking lifestyle and breast cancer. The RENEW (Reach Out to Enhance Wellness) study enrolled 641 survivors of breast, prostate, and colon cancers. Key eligibility criteria included age 65, body mass index 25 kg/m, sedentary activity pattern, and cancer diagnosis at least 5 years before enrollment. The study employed a cross-over design; participants were randomly assigned to immediate participation in a 1-year telephoneand print materials–based lifestyle intervention, designed to increase physical activity and improve dietary quality, or to delayed participation after a 1-year control period. The primary end point was change in physical functioning. A previous report demonstrated that intervention-group participants experienced significantly less decline in their functional status, improvements in dietary quality, increased physical activity, and modest weight loss, as compared with control participants. The updated report from the RENEW study shows that favorable changes in physical activity, dietary behaviors, and weight were maintained in the immediate intervention group 1 year after the discontinuation of the lifestyle intervention. Additionally, the delayed intervention group experienced significant changes in physical functioning, weight, dietary quality, and physical activity during their participation in the lifestyle intervention. These data provide key information on the durability of telephone-based lifestyle coaching. However, there are important caveats, including the small proportion of eligible individuals who opted to participate in the study (approximately 6%), the 25% attrition rate at 2 years, and the fact that all study measures, including weight, were selfreported. Despite these caveats, the efficacy of the RENEW intervention is consistent with that of other large-scale trials of distanced-based lifestyle interventions, including the WHEL study, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 19 JULY 1 2012

Prognosis following the use of complementary and alternative medicine in women diagnosed with breast cancer

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 (WHEL) study. 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 of 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.