Women's Healthy Eating And Living Research Articles

P3-09-01: Change in Carbohydrate Intake and Breast Cancer Prognosis.

Abstract Breast tumors over express insulin-like-growth-factor receptors (IGF-IR), and levels of expression may be inversely related to tumor grade. Dietary factors, particularly carbohydrate intake, may stimulate activation of IGF-1R and affect prognosis. METHODS: Data are from N=2,651 women in the Women's Healthy Eating and Living (WHEL) Dietary Intervention trial, a plant based intervention trial that did not have a carbohydrate goal. All women were diagnosed with breast cancer within the previous 4 years. Carbohydrate dietary intake data were extracted from multiple 24-hour dietary recalls at study entry and one year, and were compared by recurrence status. Time to recurrence was modeled on year-one change in carbohydrate intake adjusted for baseline intake, menopausal status, and disease, treatment, and study characteristics. RESULTS: Baseline carbohydrate intake was 233 g/day. Women who recurred had a mean increase in carbohydrate intake over the first year, compared to those who did not recur (2.3 vs. −2.7 g/day; p=0.188). Change in starch intakes accounted for 48% of the change in carbohydrate intake (R-squared: 48%; p<0.001). Baseline starch intake did not differ by recurrence status (95.8 g/day; p=0.219). Mean year-one change in starch intake was −4.1 g/day among women who recurred vs. −8.7 g/day among women who did not recur (p=0.015). Year-one change in starch intake was independent of the study intervention (p=0.326). In the adjusted model, a 5-g/day increase in starch related to a 3% increased risk of recurrence (HR=1.03; 95% CI 1.01 - 1.06; p=0.017). The increased risk was limited to women diagnosed with low grade tumors (Table 1). DISCUSSION: Dietary modifications targeting starch intake warrant further investigation as a preventive measure against breast cancer recurrence. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-01.

Soy Food Consumption and Breast Cancer Prognosis

Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer.

Sex Hormone Concentrations and the Risk of Breast Cancer Recurrence in Postmenopausal Women without Hot Flashes

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, antiestrogen 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 versus 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.

Highlights of This Issue

Breast cancer incidence rates among U.S. non-Hispanic white women decreased by ∼7% between 2002 and 2003, related to a drop in postmenopausal hormone therapy use. Although several studies have reported that breast cancer incidence rates have continued to decline, none of these studies exclusively examined the trend after 2003. To address this, DeSantis and colleagues examined SEER registries from 2000 to 2007 and National Health Interview Survey data from 2003, 2005, and 2008. They report that the sharp decline in breast cancer incidence rates among non-Hispanic white woman that occurred between 2002 and 2003 did not continue through 2007, although hormone therapy use continued to decrease. Future studies will be necessary to better understand these breast cancer trends.The low incidence of sarcomas makes it difficult to discern heritable risks for any individual sarcoma subtype. To overcome this, Jones and colleagues grouped cases from the Utah Cancer Registry and the Utah Population Database as either complex genotype/karyotype sarcomas or balanced translocation sarcomas to calculate risks for relatives of sarcoma patients. Although there was no evidence for excess relatedness for the balanced translocation sarcomas, there was strong familiarity among complex genotype sarcomas. This study indicates that genetics may play a key role in complex genotype sarcomagenesis.Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori (H. pylori) isolates may explain the disparity. To explore this, Epplein and colleagues assessed serum levels of antibodies against different H. pylori proteins as well as African and European admixtures in African American and white study participants. African American race was associated with 2- to 6-fold increased odds for the presence H. pylori proteins. Compared with whites, African Americans with “high” African ancestry had 5.2-fold increased odds of H. pylori sero-positivity. Among African Americans, “high” African ancestry had 3.4-fold increased odds of H. pylori sero-positivity. These results provide a framework for better detection and prevention of gastric cancer in African Americans.Although earlier clinical studies suggested that soy may promote breast tumor growth, recent studies demonstrate that soy-containing foods are not adversely related to breast cancer prognosis. To examine this, Caan and colleagues used data from the Women's Healthy Eating and Living (WHEL) study to examine the effect of soy intake on breast cancer prognosis. They found that as soy intake increased, risk of death decreased. This study provides further evidence that clinicians no longer need to advise against soy consumption for women diagnosed with breast cancer.

Abstract 5021: Physical health scores and breast cancer outcomes in the ABC Pooling Project

Abstract Background: Of the two health-related quality of life domains measured by the SF-36 (mental health and physical health), the physical health score (PHS) has been associated with all cause mortality, and recently with additional breast cancer events. This PHS includes subscales for self-perceived physical functioning, general health, bodily pain, and role limitations due to physical problems and is known to be a marker for a number of co-morbidities. Methods: Three of the four cohorts that form the After Breast Cancer (ABC) Pooling Project measured health-related quality of life using the SF-36 after cancer diagnosis. These cohorts were the Women's Healthy Eating and Living (WHEL) Study, the Nurses’ Health Study (NHS), and the Shanghai Breast Cancer Survival Study (SBCSS). Using Cox proportional hazards models controlled for cancer stage and grade, we examined the relationship between PHS with disease-free and overall survival in 9387 early stage (I-III) breast cancer survivors. The post-diagnosis SF-36 measurement took place between 1991 and 2006 and the median follow-up time was 7.8 years. Poor physical health was defined as a non-normalized score of 76.4 as previously published by the WHEL study. We also report the association between PH and co-morbidities. Results: The pooled HR (95% CI) for additional breast cancer events was 1.27(1.12, 1.44) with significant findings in each of the two US cohorts: Nurses’ Health Study 1.31(1.07-1.61) and WHEL study 1.28(1.08-1.51). A similar effect size was seen in SBCSS only, with the measurement taken during or immediately after cancer treatment. However, mostly likely due to the much shorter follow-up in this study, it did not reach statistical significance (HR=1.22 95% CI 0.80-1.86). In all cohorts, low PHS was strongly associated with higher BMI. In overweight/obese WHEL participants, low compared to adequate PHS scores were significantly associated with much lower levels of physical activity (p<.0001), 64% higher reported insomnia, a 50% higher prevalence of hypertension and diabetes, and a twofold higher prevalence of arthritis. Conclusion: The importance of the PHS as a predictor of future breast cancer events and overall survival appears to be confirmed in these observational studies. Interventions to improve the PHS and prognosis might target weight control, physical activity and sleep management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5021. doi:10.1158/1538-7445.AM2011-5021

Tamoxifen Metabolite Concentrations, CYP2D6 Genotype, and Breast Cancer Outcomes

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.

Classification of CAM Use and Its Correlates in Patients With Early-Stage Breast Cancer

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. The authors used a comprehensive system to classify CAM users and test differences in demographic, lifestyle, quality of life, and cancer characteristics among them. Participants were 2562 breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study, aged 28 to 74 years. A structured telephone interview assessed CAM use, questioning about specific CAM practices, and whether use was related to cancer. This study 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 and 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.

Was race a factor in the outcomes of the Women's Health Eating and Living Study?

The objective of this study was to determine whether women who were 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. For this secondary analysis, the authors used data from 3013 women who were self-identified as Asian American, African American, Hispanic, or white and who were assigned randomly to a dietary intervention or a 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 daily) than Asians and whites at baseline (all P < .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 daily), fruit (+1.1 servings daily), and vegetables (+1.6 servings daily; all P < .05). Despite improvements in the overall dietary pattern of these survivors, the intervention did not significantly influence second breast cancer events or 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.

IGF-1 and risk of additional breast cancer in the WHEL study

IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer survivors in the Women's Healthy Eating and Living (WHEL) study. A nested case-control design was used to match breast cancer cases (who had an additional breast cancer event) to controls. Baseline blood samples from 510 matched cases and controls were analyzed for IGF1 levels; a subset of 188 pairs were analyzed for five other hormones and binding proteins. Median follow-up was 7.3 years. Matching was on recruitment site, cancer stage, age at cancer diagnosis, dates of cancer diagnosis, and randomization. Cox proportional hazards regression models, stratified on case-control pair, were used to assess the associations. Insulin, IGFBP-1, IGFBP-3, leptin, and adiponectin did not significantly predict recurrence of breast cancer. IGF1 was positively, but not significantly, associated with recurrence (hazard ratio (HR): 1.33 (95% confidence interval (CI) 0.98-1.81)) in the unadjusted analyses. Adjusting for menopausal status and tamoxifen use attenuated the HR to 1.07 (95% CI 0.76-1.40). Analyses of case-control pairs with discordant tamoxifen use show opposing HR: IGF1 predicts higher risk of recurrence if cases did not receive tamoxifen treatment. In conclusion, no significant association was found between IGF1 levels, or other related factors, and risk of additional breast cancer among breast cancer survivors. Tamoxifen can confound analysis of IGF1 and recurrence. This supports re-evaluating significance of IGF1 to breast cancer recurrence.

Vitamin D and breast cancer recurrence in the Women’s Healthy Eating and Living (WHEL) Study

There is a paucity of research evaluating the relation between vitamin D and recurrence of breast cancer after treatment. This study was designed to evaluate the associations between circulating concentrations of 25-hydroxyvitamin D [25(OH)D] and dietary, supplemental, and total intake of vitamin D and recurrent or new breast cancer events within the Women's Healthy Eating and Living (WHEL) Study. A prospective cohort study design (n = 3085) was used to evaluate the relation between dietary, supplemental, and total vitamin D intake and recurrent breast cancer, and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence. No relation between 25(OH)D and breast cancer recurrence was observed. Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL, adjusted odds ratios (95% CI) for breast cancer recurrence were 1.14 (0.57, 2.31) for those with concentrations < 10 ng/mL, 1.00 (0.68-1.48) for concentrations ≥ 10 and < 20 ng/mL, and 1.05 (0.76, 1.47) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local, regional, or distant recurrence or death. Vitamin D intake was not related to breast cancer recurrence overall, although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence (P for trend = 0.02). These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer. This trial is registered at clinicaltrials.gov for the WHEL Study as NCT00003787.

Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study

The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (⁻x, SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55-0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41-0.77 for total vegetables and 0.65, 95% CI 0.47-0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32-0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.

Physical and mental health correlates of pregnancy following breast cancer

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 (WHEL) study (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 with 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.

Depressive symptoms among young breast cancer survivors: the importance of reproductive concerns

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. 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 postdiagnosis 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 postdiagnosis. 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.

Abstract A111: Sweetened beverages, sweetened foods, glycemic load, and breast cancer recurrence

Abstract Background: The role of sweetened food and beverage intake in breast cancer recurrence has been largely unexplored despite mechanistic evidence that these dietary factors may be associated with elevated glycemic load, insulin levels and proinflammatory response. Objective: To assess risk for recurrent or a new primary breast cancer event among 2832 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study in relation to baseline sweetened beverage and sweetened food intakes and glycemic index/glycemic load. Design: Prospective sub-group analysis of dietary GI, GL, white bread/rolls/crackers, sweet food and sweetened beverage intakes, as assessed using the Arizona Food Frequency Questionnaire (AFFQ), and new breast cancer events (N=471). Descriptive statistics and Cox regression analysis, adjusted for confounding variables, were performed to assess hazard ratio for recurrence risk by dietary exposure. Results: Study subjects consumed, on average, 281.7±111.4 g/d carbohydrate (CHO) and 25.2±12.3 g/d of dietary fiber and had an estimated GL of 129.5±52.2.While GI and GL were not significantly associated with breast cancer events, postmenopausal women who reported a higher intake of sweetened beverages demonstrated a significant elevation in risk for recurrent disease (HR 1.46; 95% CI,1.07–1.98). Intake of sweetened beverages was greater among minority women and was associated with higher body mass index and lower reported physical activity suggesting sweetened beverage intake may be a surrogate of other risk factors. Conclusions: High intake of sweetened beverages, including carbonated beverages and sweetened fruit drinks, is associated with an increased risk for breast cancer recurrence among postmenopausal women previously treated for early stage disease. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A111.

A qualitative investigation of breast cancer survivors' experiences with breastfeeding.

IntroductionThis is an exploratory, qualitative investigation of breast cancer survivors’ experiences with breastfeeding. Previous studies have focused on the physiology of lactation after surgery and treatment, but have not explored factors influencing breastfeeding decisions and behavior.MethodsWe used purposeful sampling to identify 11 breast cancer survivors who had a child after their diagnosis and treatment. Participants were recruited from among those in the Women’s Healthy Eating and Living (WHEL) study and a Young Survival Coalition (YSC) affiliate. We conducted semi-structured, open-ended telephone interviews lasting 45–75 min. We used social cognitive theory (SCT) to structure questions regarding influences on breastfeeding behavior. We transcribed interviews and used cross-case, inductive analysis to identify themes.ResultsTen of 11 participants initiated breastfeeding. The following main themes emerged: 1) Cautiously hopeful, 2) Exhausting to rely on one breast, 3) Motivated despite challenges, 4) Support and lack of support, and 5) Encouraging to others.Discussion/ConclusionsStudy participants were highly motivated to breastfeed but faced considerable challenges. Participants described problems that are not unique to women with breast cancer, but experienced these to a much greater degree because they relied mostly or entirely on one lactating breast. This study revealed a need for improved access to information and support and greater sensitivity to the obstacles faced by breast cancer survivors.Implications for cancer survivorsResults of this qualitative analysis indicate that interventions to support the efforts of breast cancer survivors who are interested in breastfeeding are warranted. Additional research would aid in the development of such interventions.

Diet and breast cancer prognosis: making sense of the Women's Healthy Eating and Living and Women's Intervention Nutrition Study trials.

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. Women's Intervention Nutrition Study and Women's Healthy Eating and Living (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. Women's Intervention Nutrition Study 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 more important distal recurrences. This review considers only WHEL postmenopausal women to aid a direct comparison with Women's Intervention Nutrition Study. 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 subgroup 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 subgroups. Further investigation of mechanisms for such selective action is needed.

Hot flashes are associated with CYP2D6 genotype in breast cancer survivors taking tamoxifen.

Abstract Abstract #6045 Background: We have previously shown that participants in the Women's Healthy Eating and Living (WHEL) study comparison group who reported hot flashes after breast cancer treatment had more favorable disease-free survival than women who did not report hot flashes. However, this was not the case in the intervention group. The polymorphic CYP450 enzyme CYP2D6 catalyzes the conversion of tamoxifen (TAM) to one of its key active metabolites, endoxifen. Some studies have suggested that certain genetic variants of CYP2D6 are associated with a decreased likelihood of hot flashes, reduced endoxifen levels and an increased risk of disease recurrence in women receiving adjuvant TAM therapy. This analysis was performed to estimate the association between CYP2D6 genotype and hot flashes in early stage breast cancer survivors who took adjuvant TAM in the WHEL study.&amp;#x2028; Methods: The WHEL study was a randomized trial of a dietary intervention in breast cancer survivors, who enrolled in the study within 4 years of diagnosis from 1995-2000. Participants self-reported TAM use, hot flash severity and menopausal status at study entry. Clinical characteristics (tumor stage, estrogen receptor status, chemotherapy) were extracted from medical records. Blood samples were obtained by venipuncture, separated and stored at -80 deg. DNA was extracted from stored buffy coat and analyzed using the Roche AmpliChip CYP450 Test. Women were classified according to their predicted CYP2D6 phenotype as Extensive (EM), Heterozygous Extensive (Het EM), Intermediate (IM), Poor (PM), or Ultrarapid (UM) Metabolizers.&amp;#x2028; Results: Overall, 1434 WHEL participants had verified estrogen receptor-positive stage I or II breast cancers and reported taking TAM at baseline for at least 4 months. A total of 1411 women were successfully genotyped and their CYP2D6 phenotypes were classified as follows: 468 EM (33.2%); 665 Het EM(47.1%), 164 IM (11.6%), 86 PM (6.1%) and 28 UM (2.0%). In univariate analyses, there was a significant difference among CYP2D6 genotype in relation to hot flashes reported at baseline: 79.8% of EMs, 76.3% of Het EMs, 80.1% of IMs, 63.9% of PMs, and 75% of UMs reported hot flashes (χ2= 11.3, p=0.02). After controlling for age, menopausal status, and time since diagnosis, the PM group was half as likely to report hot flashes as the referent EM group (OR= 0.46; 95% CI= 0.28-0.78; p=0.003). Additional analyses of serum endoxifen levels and associations with disease outcome are underway.&amp;#x2028; Conclusion: In the WHEL study, women who were classified as Poor Metabolizers of TAM, based on their CYP2D6 genotype, were half as likely as Extensive Metabolizers to report experiencing hot flashes while receiving adjuvant TAM treatment for early stage breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6045.

Physical health and cancer-free survival in women diagnosed with breast cancer.

Abstract Abstract #1114 Background: A protective effect of physical activity (PA) after breast cancer diagnosis is not a consistent finding across studies. It is possible that a beneficial effect from higher PA levels may be limited to a sub-group defined by level of physical health (PH). We investigated the role of PA and PH in predicting breast cancer free survival.&amp;#x2028; Methods: The Women's Healthy Eating and Living (WHEL) Study enrolled 3088 women within 4 years of early stage breast cancer diagnosis from 1995 to 2000. At study entry, participants completed the RAND-36 Health Survey that includes a physical health summary score comprised of physical functioning, general health, pain, and role limitations due to PH subscales. PA was assessed with a questionnaire developed for the Women's Health Initiative and validated for the WHEL Study. Additional breast cancer events (recurrence or new breast primary; n = 518) were queried semi-annually through June 2006 and confirmed by oncologist review of medical records. Multivariate Cox modeling was used to associate PA and PH with additional breast cancer events, adjusting for demographic, lifestyle, tumor, and treatment-related covariates.&amp;#x2028; Results: In the unadjusted analysis, quartiles of PA were not related to additional breast cancer events, whereas the PH summary score was [Hazard ratios (HR) for quintiles (Q), Q1 (reference): Q2= 0.90, Q3 =0.69, Q4=0.55, and Q5=0.74; p-values = 0.45, 0.01, &amp;lt;0.0001, and 0.03 respectively]. For further analysis, we grouped the bottom two quintiles (“poor” PH) and the upper three quintiles (“adequate” PH). In the adjusted Cox model, poor PH was associated with a 42% higher risk of additional breast cancer events (HR: 1.42, 95% CI: 1.15, 1.74).&amp;#x2028; We compared participants in poor versus adequate PH group. Those in the poor PH group were much more likely to report role limitations (91% vs. 17%) and bodily pain (44% vs. 4%). They were much more likely to be minimally physically active (&amp;lt;90 MET-minutes/week) (23% vs. 12%, p&amp;gt;0.0001) and obese (37% vs. 19%; p &amp;lt;0.0001). We included an interaction term into the Cox model using the binary PH measure and a binary PA measure (540 ≥ vs. &amp;lt; 540 MET-minutes/week, equivalent to 30 minutes moderate walking 6 days/week). Compared to those with adequate PH and higher PA, only those with poor PH and lower PA were at increased risk (HR 1.46, 95% CI: 1.15, 1.74).&amp;#x2028; Among those in this higher risk subgroup (poor PH, lower PA), the majority indicated that they would not be limited a lot in walking a mile (79%) or climbing several flights of stairs (73%) and a substantial proportion indicated that they could undertake vigorous activity (37%).&amp;#x2028; Discussion: Breast cancer survivors categorized as in poor PH had a 42% worse prognosis than those in adequate PH. This was particularly the case for those in poor PH who did less PA. This suggests that a motivational intervention to increase physical activity in this subgroup may improve their prognosis following breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1114.

The importance of updating the family history of breast cancer survivors.

Abstract Abstract #1097 BACKGROUND: The cancer family history is the most important tool in identifying women who may be at high risk of having the hereditary breast-ovarian cancer syndrome (HBOCS) caused by mutations in the BRCA1 and BRCA2 genes. While many breast cancer patients may be asked about their family history at the time of their initial diagnosis, it is not known how many women initially classified as low risk of HBOCS become high risk of HBOCS over time, as new cancers are diagnosed in their relatives.&amp;#x2028; PURPOSE: 1)To determine how the prevalence of "high risk" cancer family histories changes over time in cancer patients, and; 2) To determine how many breast cancer survivors at high risk for HBOCS self-report having had genetic testing for BRCA1/2.&amp;#x2028; METHODS: Breast cancer survivors in the Women's Healthy Eating and Living (WHEL) study provided detailed family history data at baseline and again at study closure. The Myriad prevalence tables were used to categorize survivors as "high risk" of HBOCS if their risk of having a mutation in BRCA1/2 was 10% or greater.&amp;#x2028; RESULTS: At baseline, 8.2% of 2508 survivors were classified as high risk. At follow-up (avg. 7.5 years later), an additional 5.8% of women became high risk due to new cancers in their families. Among high-risk survivors, 15% reported that they had never heard of BRCA testing. Of the 85% who had heard of testing, 23% reported that they had been tested.&amp;#x2028; CONCLUSIONS: The prevalence of "high risk" cancer family histories increased by 70% in a cohort of breast cancer survivors over 7.5 years. It is important for clinicians to identify high-risk families not only at initial diagnosis, but to update the family history periodically. A substantial proportion of high-risk women had never heard of BRCA1/2 testing, and could benefit from genetic counseling to discuss the cancer risk in their families. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1097.

Disclosure to Physicians of CAM Use by Breast Cancer Patients: Findings From the Women's Healthy Eating and Living Study

Physician awareness of their patients' use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner--perceived as a physician-like authority figure--but does not disclose this to their physician. Therefore, this study investigated the extent of nondisclosure in a large cohort of cancer patients. CAM use in participants of the UCSD Women's Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women aged 18-70 years who had completed treatment for invasive breast cancer between 1995 and 2000, is investigated. Data regarding CAM use and disclosure were collected via a telephone-administered questionnaire in 2003-2004. This questionnaire asked about different CAM modalities, including those requiring a "skilled CAM practitioner" (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data were obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using 2 tests for categorical variables, and t tests for continuous variables. Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (P=.047) and study site (P=.039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education. Overall, moderately high rates of physician disclosure of CAM use for all modalities except chiropractic were observed. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient--physician communication regarding CAM use.