Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: As one of the 10 most common cancers in the United States, bladder cancer is the most expensive cancer to treat. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed. However, 50% to 80% of NMIBC recurs within 5 years, and 15% to 30% progresses with poor survival. Besides life-long surveillance, current treatment is limited. Preclinical and epidemiologic evidence suggest that dietary isothiocyanates (ITCs) in cruciferous vegetables (Cruciferae) could be a noninvasive and cost-effective strategy to improve NMIBC prognosis. Yet, a Cruciferae intervention that increases ITC exposure in NMIBC survivors has not been tested. Thus, the primary aim of this study was to test the effect of a Cruciferae intervention on urinary ITC levels and Cruciferae intake in NMIBC survivors. PATIENTS AND METHODS: We conducted a 2-arm, double-blinded, randomized controlled trial to test the efficacy of a Cruciferae intervention against a general fruit and vegetable intervention (control) for NMIBC survivors. Both 6-month interventions consisted of mailed educational materials, a live call with staff to review the materials, and 11 interactive voice response calls. We anticipated that our Cruciferae intervention (Power to Redefine Your Health [POW-R Health]) would increase Cruciferae intake to 1 cup/day (secondary outcome), thus raising urinary ITC levels to 10 µM (primary outcome) from baseline to 6-month follow-up. RESULTS: We randomized 49 patients with NMIBC diagnosed in 2018 through 2019, and retained 42 patients at 6-month follow-up. The treatment group reported 0.94 cups (95% CI, 0.24-1.65; P=.010) higher Cruciferae intake (treatment, 1.37 ± 1.19 cups vs control, 0.56 ± 0.72 cups) and increased urinary ITC levels by 11.1 µmol/g creatinine (treatment, 26.2 ± 20.9 vs control, 7.8 ± 11.5; P=.027) at 6-month follow-up compared with the control group. CONCLUSIONS: Our dietary intervention is the first to significantly increase Cruciferae intake and urinary ITC levels in NMIBC survivors, demonstrating an increase in ITC to levels that significantly decrease risk of disease-specific survival. A future randomized controlled trial testing POW-R Health on bladder cancer recurrence and progression is warranted. If proven to improve bladder cancer outcomes, our intervention has the potential to be a noninvasive, cost-effective, easily accessible way for NBMIC survivors to improve their bladder cancer prognosis.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Glycemic Index, Glycemic Load, and Risk of Ovarian Cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cohort.

BACKGROUND: Ovarian cancer is the fifth most common cause of cancer death among women in the US, yet few modifiable risk factors have been established. Diets high in glycemic index (GI) and glycemic load (GL) have been linked to several cancers, but epidemiologic studies of ovarian cancer have yielded inconsistent results. OBJECTIVE: In this study, we aimed to examine associations between GI or GL and ovarian cancer. METHODS: We used prospective data from the Prostate, Lung, Colorectal, and Ovarian cohort. GI and GL were calculated from validated FFQs. Participants were women who were aged 60 to 74 y, did not have a history of cancer, and had both ovaries. Cox proportional hazard models were used to calculate HRs and 95% CIs for risk of ovarian cancer associated with quartiles of GI and GL. Analyses were performed separately for those who completed the dietary questionnaire at baseline (DQX) or later in the study (DHQ). RESULTS: From the DQX sample set, 181 cases were identified among 24,633 women with median follow-up of 12.1 y; there were 211 cases among 42,410 women in the DHQ set, with median follow-up of 8.9 y. After adjusting for age at dietary questionnaire completion, year of randomization, year of questionnaire, study center, and oral contraceptive use, the risk of ovarian cancer decreased by 43% (HR: 0.57; 95% CI: 0.37, 0.88) among those in the highest compared with those in the lowest quartile of GL (DQX). Those in the highest compared with those in the lowest quartile of GI (DHQ), had a 38% lower risk (HR: 0.62; 95% CI: 0.42, 1.00). CONCLUSIONS: We observed lower risk of ovarian cancer associated with higher GI and GL. Results should be interpreted with caution as they may have been influenced by limitations including lack of variability in dietary intake. Additional studies are needed to better understand what is driving these associations.

Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

BACKGROUND: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. OBJECTIVES: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. METHODS: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. RESULTS: We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary ß-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. CONCLUSIONS: Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.

Dietary phytoestrogen intakes of adult women are not strongly related to fecundability in 2 preconception cohort studies.

BACKGROUND: Phytoestrogens are plant-derived hormonally active compounds found in soy, cruciferous vegetables, nuts, and seeds. Although phytoestrogens have been associated with altered endogenous hormonal activity, luteal phase deficiency, and reduced endometrial decidualization, the literature reporting examinations of phytoestrogen intake and fertility presents mixed findings. OBJECTIVES: We sought to evaluate prospectively the association between dietary phytoestrogen intake (isoflavones, lignans, and coumestans) and fecundability, the per-cycle probability of conception, in 2 cohorts of women planning pregnancy. METHODS: Pregnancy Study Online (PRESTO) and Snart Foraeldre (SF) are parallel web-based preconception cohort studies of women from North America and Denmark, respectively, who are trying to conceive. Participants complete an online baseline questionnaire on sociodemographic, lifestyle, and medical factors. We ascertained intake of individual phytoestrogens from validated FFQs. We measured fecundability using data on menstruation and pregnancy status from bimonthly follow-up questionnaires. We analyzed data from 4880 PRESTO and 2898 SF female study participants who had been attempting conception for ≤6 cycles at study entry. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs. RESULTS: Phytoestrogen intake varied across cohorts, yet was associated with higher socioeconomic status and healthier behaviors in both cohorts. After adjustment for potential confounders, phytoestrogen intake was not substantially associated with fecundability in either cohort. We observed some evidence of improved fecundability with increasing isoflavone intake among women age ≥30 years in PRESTO (FR: 1.12; 95% CI: 0.94, 1.34, for comparison of ≥90th with <25th percentile intake) and SF (corresponding FR: 1.19; 95% CI: 0.92, 1.55). Lignan intake was associated with slightly increased fecundability in SF (FR for comparison of 75th to 90th with <25th percentile: 1.10; 95% CI: 0.96, 1.26), but decreased fecundability in PRESTO (FR for comparison of ≥90th with <25th percentile: 0.83; 95% CI: 0.72, 0.97). CONCLUSIONS: We did not observe strong associations between phytoestrogen intake and prospectively-measured fecundability among North American or Danish pregnancy planners.

Cruciferous Vegetable Consumption and Stomach Cancer: A Case-Control Study.

Objective: To investigate the association between regular cruciferous vegetable intake and stomach cancer.Methods: A hospital-based, case-control study was conducted at Roswell Park Comprehensive Cancer Center in Buffalo, NY, which included 292 stomach cancer patients and 1168 cancer-free controls recruited between 1992 and 1998 as part of the Patient Epidemiology Data System (PEDS). Dietary and other epidemiologic and confounding variables were collected by questionnaire. Multivariable logistic regression analyses were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between usual pre-diagnostic cruciferous vegetable intake and stomach cancer, with adjustment for other stomach cancer risk factors and dietary characteristics.Results: We observed strong inverse associations between stomach cancer and highest versus lowest intakes of total cruciferous vegetables (OR = 0.59, 95% CI: 0.42-0.83), raw cruciferous vegetables (OR = 0.53, 95% CI: 0.38-0.73), raw broccoli (OR = 0.61, 95% CI: 0.43-0.86), raw cauliflower (OR = 0.51, 95% CI: 0.35-0.73), and Brussels sprouts (OR = 0.66, 95% CI = 0.48-0.91).Conclusions: These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer, even after considering other dietary characteristics.

Habitual recreational physical activity is associated with significantly improved survival in cancer patients: evidence from the Roswell Park Data Bank and BioRepository.

PURPOSE: The association of recreational physical activity (RPA) with mortality is well established only for breast and colon cancers and few studies have evaluated relationships for exercising before and after diagnosis, across multiple disease sites. We examined the joint associations of pre- and post- diagnosis RPA with mortality in a cohort of 5,807 patients enrolled in the Data Bank and BioRepository at Roswell Park. METHODS: Patients were classified into one of four activity categories (habitually active, increased activity after diagnosis, decreased activity after diagnosis, habitually inactive). Cox proportional hazards models were used to estimate the associations of activity status with mortality. RESULTS: In comparison to patients who were habitually inactive, habitually active patients experienced a 39% decreased hazard of all-cause mortality (HR = 0.61, 95% CI 0.54-0.69) and a 36% decreased hazard of cancer-specific mortality (HR = 0.64, 95% CI 0.56-0.73). Previously inactive patients who began exercising after diagnosis experienced a 28% decreased hazard of all-cause (HR = 0.72, 95% CI 0.59-0.89) and cancer-specific mortality (HR = 0.72, 95% CI 0.57-0.91) in comparison to patients who remained inactive. Patients engaging in 3-4 sessions/week experienced the greatest survival advantages, but 1-2 sessions/week also yielded significant survival advantages in comparison to inactivity. CONCLUSION: Low-to-moderate frequency pre- and post-diagnosis RPA was associated with significantly decreased mortality in patients diagnosed with a variety of malignancies. These observations solidify the clinical and public health importance of the message that some regular activity is better than inactivity, which is particularly encouraging, given that cancer survivors can be overwhelmed by current daily physical activity recommendations.

Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial.

Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.

Associations between self-reported diet during treatment and chemotherapy-induced peripheral neuropathy in a cooperative group trial (S0221).

BACKGROUND: The pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) is not well understood. Currently, dose reduction is the only recommendation for alleviating symptoms, often leading to premature treatment cessation. The primary aim of this analysis was to determine the association between components of diet during taxane treatment for breast cancer and change in CIPN symptoms over treatment. METHODS: Women with stage II or III invasive breast cancer were enrolled into an ancillary study to the North American Breast Cancer Intergroup phase III trial (S0221) led by the Southwest Oncology Group (SWOG). Questionnaires including a food frequency questionnaire and the Functional Assessment of Cancer Treatment Gynecologic Oncology Group-Neurotoxicity were administered to assess diet and neuropathic conditions at baseline and during chemotherapy. Ordinal regression was used to estimate odds ratios (ORs) for associations between various food groups and change in neuropathy score (< 10%, 10-30%, > 30%) (n = 900). RESULTS: The odds of worse neuropathy decreased by 21% for each increase in tertile of grain consumption (OR = 0.79, 95% CI 0.66-0.94, p = 0.009). We also observed a nominal 19% increase with higher consumption of citrus fruits (OR = 1.19, 95% CI 1.01-1.40, p = 0.05). CONCLUSIONS: Distinguishing between those who experienced a moderate and a severe change in neuropathy, we found that citrus fruit and grain consumption may play a role in the severity of symptoms. Since there are no existing dietary recommendations for the management of CIPN, further research is needed to investigate whether there may be certain foods that could worsen or alleviate neuropathy symptoms associated with treatment for breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03413761 . Registered retrospectively on 29 January 2018.

Usual Cruciferous Vegetable Consumption and Ovarian Cancer: A Case-Control Study.

Ovarian cancer is the fifth leading cause of cancer-related deaths among women, primarily due to diagnosis at late stages. Therefore, identification of modifiable risk factors for this disease is warranted. Using the Patient Epidemiology Data System (PEDS), collected from 1981 to 1998 at Roswell Park Cancer Institute, Buffalo, NY, we conducted a hospital-based, case-control analysis of self-reported cruciferous vegetable intake and ovarian cancer among 675 women with primary, incident ovarian cancer, and 1275 without cancer. Cruciferous vegetable intake was queried using a 44-item food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression, adjusting for age, body mass index (BMI), education, smoking status, parity, family history of ovarian cancer, total fruit consumption, total meat consumption, and total noncruciferous vegetable consumption. We observed a significant inverse association for women with highest vs. lowest intakes of total vegetables (OR = 0.65, 95% CI = 0.46-0.92), cooked cauliflower (OR = 0.82, 95% CI = 0.67-0.99), and cooked greens (OR = 0.63, 95% CI = 0.46-0.86) and an inverse, dose-dependent association between cooked cruciferous vegetables intake and ovarian cancer (for each additional ten servings per month, OR = 0.85, 95% CI = 0.76-0.96). These findings suggest that a diet that includes cruciferous vegetables could be an important modifiable risk factor for ovarian cancer.

Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium.

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥ 35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥ 45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥ 10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.

Dietary lignan intake and androgen receptor expression in breast tumors.

PURPOSE: Lignans, a class of phytoestrogen commonly found in the Western diet, have been linked to decreased breast cancer risks in epidemiologic studies. Similar to estrogen receptors, the androgen receptor (AR), a prognostic factor in breast tumors, may be affected by lignans. However, few studies have investigated this link in the context of breast cancer etiology. We evaluated the relationship between dietary lignan intake and AR expression in incident breast tumors. METHODS: Tumor tissue, epidemiological, and clinical data were collected from 216 women with incident, primary, histologically confirmed breast cancer enrolled in the Roswell Park Cancer Institute (RPCI) Data Bank and BioRepository (DBBR). On average, three tumor cores from each participant were assembled into a tissue micro array. After immunohistochemical staining, a trained RPCI pathologist determined AR status of each core. Lignan intake was calculated from a food frequency questionnaire collected upon enrollment into the DBBR. RESULTS: We observed a weak positive association between dietary lignans and AR expression [ß (SE) 27.6 (17.0), p 0.10], and there was no significant difference in lignan intake across categories of AR expression (p = 0.09, R (2) = 0.35). CONCLUSION: Our results do not support a clear relationship between dietary lignan intake and AR expression. This investigation is the first, to our knowledge, to examine dietary lignan intake and AR expression in breast tumors. Further research is needed within a larger, more representative sample to determine whether lignan intake is truly associated with AR expression.

Dietary supplement use among participants of a databank and biorepository at a comprehensive cancer centre.

OBJECTIVE: We assessed the prevalence, patterns and predictors of dietary supplement use among participants of the databank and biorepository (DBBR) at a comprehensive cancer centre in western New York. DESIGN: Archived epidemiological questionnaire data were obtained from the DBBR at Roswell Park Cancer Institute. Descriptive statistics and logistic regression explored the prevalence, patterns and predictors of lifetime use of four common supplements (multivitamins, vitamin C, vitamin E and calcium) and use of multivitamins, sixteen single vitamins/minerals and eighteen herbal/specialty supplements within the previous 10 years. SETTING: Western New York, USA. SUBJECTS: DBBR participants (n 8096) enrolled between December 2003 and July 2012 were included in these analyses: 66.9 % (n 5418) with cancer, 65.6 % (n 5309) women, mean age for patients v. cancer-free controls 59.9 (SD 12.6) years and 50.7 (SD 15.4) years, respectively. RESULTS: Overall, 54.4 % of DBBR participants reported lifetime use of one or more supplements and 63.1 % reported use of one or more supplements within the previous 10 years (excluding multivitamins). Multivitamin use was high in this sample (lifetime: 64.1 %; 10 years: 71.3 %; current: 51.8 %). Supplementation was higher among cancer-free controls than cancer patients. Vitamin C, calcium and fish oil were the most common single vitamin, mineral and specialty product, respectively. CONCLUSIONS: A consistently high and increasing proportion of dietary supplement use over time remains clear. Supplementation is prevalent among cancer patients and may even be higher than predicted in cancer-free individuals. Further studies should assess the safety and efficacy of specific supplements in reducing disease risk.

Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women.

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl-group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case-control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (fourth vs. first quartile: OR = 0.57, 95% CI, 0.33-1.00; p for trend = 0.06) and for ER-positive tumors (fourth vs. first quartile: OR = 0.58, 95% CI, 0.36-0.93; p for trend = 0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (fourth vs. first quartile: OR = 1.53, 95% CI, 1.06-2.21; p for trend = 0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal status or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation.

Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study.

PURPOSE: It has long been held that parity reduces risk of breast cancer. However, accumulating evidence indicates that the effects of parity, as well as breastfeeding, may vary according to estrogen receptor (ER) status. We evaluated these associations in a case-control study among African-American women in New York City and New Jersey. METHODS: In the Women's Circle of Health Study, including 786 African-American women with breast cancer and 1,015 controls, data on reproductive histories were collected from in-person interviews, with tumor characteristics abstracted from pathology reports. We calculated number of live births and months breastfeeding for each child, and examined each in relation to breast cancer by ER status, and for triple-negative (TN) breast cancer. RESULTS: Although associations were not statistically significant, having children was associated with reduced risk of ER+ breast cancer [odds ratio (OR) 0.82, 95 % confidence interval (CI) 0.58-1.16], but increased risk of ER- tumors, with associations most pronounced for TN breast cancer (OR 1.81, 95 % CI 0.93-3.51). Breastfeeding gave no additional benefit for ER+ cancer, but reduced the risk of ER- disease associated with parity. CONCLUSIONS: Accumulating data from a number of studies, as well as our own in African-American women, indicate that the effects of parity and breastfeeding differ by ER status. African-American women are more likely to have children and not to breastfeed, and to have ER- and TN breast cancer. It is possible that breastfeeding in this population could reduce risk of more aggressive breast cancers.

Intake of energy-dense foods, fast foods, sugary drinks, and breast cancer risk in African American and European American women.

Limiting energy-dense foods, fast foods, and sugary drinks that promote weight gain is a cancer prevention recommendation, but no studies have evaluated intake in relation to breast cancer risk in African American (AA) women. In a case-control study with 1692 AA women (803 cases and 889 controls) and 1456 European American (EA) women (755 cases and 701 controls), odds ratios (OR) and 95% confidence intervals (CI) for risk were computed, stratifying for menopausal and estrogen receptor (ER) status. Among postmenopausal EA women, breast cancer risk was associated with frequent consumption of energy-dense foods (OR = 2.95; 95% CI: 1.66-5.22), fast foods (OR = 2.35; 95% CI: 1.38-4.00), and sugary drinks (OR = 2.05; 95% CI: 1.13-3.70). Elevated risk of ER+ tumors in EA women was associated with energy-dense (OR = 1.75; 95% CI: 1.14-2.69) and fast foods (OR = 1.84; 95% CI: 1.22-2.77). Among AA women, frequent fast food consumption was related to premenopausal breast cancer risk (OR = 1.97; 95% CI: 1.13-3.43), and with ER+ tumors. Energy adjustment attenuated risk estimates in AA women, while strengthening them among EA women. Frequent consumption of energy-dense and fast foods that have poor nutritive value appeared to increase breast cancer risk in AA and EA women, with differences by menopausal status and ER status.

A pilot study comparing the effect of flaxseed, aromatase inhibitor, and the combination on breast tumor biomarkers.

Use of complementary approaches is common among breast cancer survivors. Potential interactions between aromatase inhibitors (AI) and high phytoestrogen foods, such as flaxseed (FS), are not often described. We conducted a pilot 2 × 2 factorial, randomized intervention study between tumor biopsy and resection, in 24 postmenopausal women with estrogen receptor positive (ER+) breast cancer, to assess the effects of FS and anastrozole, and possible interactions between them, on serum steroid hormone and tumor-related characteristics associated with long-term survival (Roswell Park Cancer Institute, 2007-2010). The effect of each treatment vs. placebo on outcomes was determined by linear regression adjusting for pretreatment measure, stage, and grade. Although not statistically significant, mean ERß expression was approximately 40% lower from pre- to postintervention in the FS + AI group only. We observed a statistically significant negative association (ß ± SE -0.3 ± 0.1; P = 0.03) for androstenedione in the FS + AI group vs. placebo and for DHEA with AI treatment (ß ± SE -1.6 ± 0.6; P = 0.009). Enterolactone excretion was much lower in the FS + AI group compared to the FS group. Our results do not support strong effects of FS on AI activity for selected breast tumor characteristics or serum steroid hormone levels but suggest AI therapy might reduce the production of circulating mammalian lignans from FS.

Dietary risk factors for monoclonal gammopathy of undetermined significance in a racially diverse population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma, is associated with shorter lifespan and cardiac, renal, neurologic, and immune-related comorbidities. There is little known about modifiable risk factors for this condition. To determine whether the risk of MGUS is associated with dietary factors in a racially diverse population, we conducted a US population-based case-control study from the National Health and Nutrition Examination Survey (1988-2004), which included 373 individuals with MGUS and 1406 matched controls. Diet was characterized by one 24-hour dietary recall, with gram intake of individual foods and beverages aggregated into groups. Unconditional multivariable logistic regressions were used to model associations between intake of several food groups and MGUS, with odds ratios (ORs) and 95% confidence intervals (CIs) reported for the highest relative to the lowest quantile of intake. Daily gram intake of several food and beverage groups were significantly associated with MGUS. MGUS was inversely associated with whole-grain bread, oats, and rice (OR, 0.70; 95% CI, 0.48-1.00; P < .05), fruits (excluding juice) and vegetables (OR, 0.69; 95% CI, 0.52-0.93; P = .02), vegetables (OR, 0.75; 95% CI, 0.56-0.99; P < .05), tomatoes (OR, 0.72; 95% CI, 0.51-1.00; P < .05), and cruciferous vegetables (OR, 0.44; 95% CI, 0.26-0.74; P < .01). Direct associations were observed for sugar-sweetened beverages (OR, 1.34; 95% CI, 1.00-1.78; P < .05), sugar-sweetened soft drinks (OR, 1.41; 95% CI, 1.01-1.96; P = .04), and artificially sweetened soft drinks (OR, 1.55; 95% CI, 1.04-2.33; P = .03). Our study shows that diet is potentially a modifiable risk factor for MGUS.

Alcohol intake over the life course and breast cancer survival in Western New York exposures and breast cancer (WEB) study: quantity and intensity of intake.

Alcohol intake is a risk factor for breast cancer, but the association between alcohol and mortality among breast cancer survivors is poorly understood. We examined the association between alcohol intake from all sources, assessed by cognitive lifetime drinking history, and all-cause and breast cancer mortality among women with breast cancer (N = 1,097) who participated in a population-based case-control study. Vital status was ascertained through 2006 using the National Death Index. Using Cox proportional hazards models, we computed hazard ratios for all-cause and breast cancer mortality in association with alcohol intake. We examined lifetime volume and intensity (drinks per drinking day) of alcohol consumption as well as drinking status during various life periods. Analyses were stratified by menopausal status. After adjustment for total intake, postmenopausal women with consumption of four or more drinks per drinking day over their lifetimes were nearly three times more likely to die from any cause compared to abstainers (HR 2.94, 95 % CI 1.31, 6.62). There was a similar but non-significant association with breast cancer mortality (HR 2.68, 95 % CI 0.94, 7.67). Postmenopausal women who drank one drink or fewer per drinking day between menarche and first birth had a significantly decreased hazard of all-cause (HR 0.54, 95 % CI 0.31, 0.95) and breast cancer mortality (HR 0.27, 95 % CI 0.09, 0.77). Premenopausal breast cancer survival was not associated with drinking intensity. We observed no associations between drinking status or total volume of alcohol intake and breast cancer or all-cause mortality. High-intensity alcohol consumption may be associated with decreased survival in postmenopausal women with breast cancer. Low-intensity alcohol consumption between menarche and first birth may be inversely associated with all-cause and breast cancer mortality; this period may be critical for development of and survival from breast cancer. Intensity of alcohol intake may be a more important factor than absolute volume of intake on survival in women with breast cancer.

Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers.

Immune signatures in breast tumors differ by estrogen receptor (ER) status. The purpose of this study was to assess associations between ER phenotypes and circulating levels of cytokines that co-ordinate cell-mediated [T-helper type 1 (Th1)] and humoral [T-helper type 2 (Th2)] immunity. We conducted a case-case comparison of 523 women with newly diagnosed breast cancer to evaluate associations between 27 circulating cytokines, measured using Luminex XMap technology, and breast cancer phenotypes [ER(-) vs. ER(+); triple negative breast cancer (TNBC) vs. luminal A (LumA)]. Ratios of Th1 to Th2 cytokines were also evaluated. Levels of interleukin (IL)-5, a Th-2 cytokine, were higher in ER(-) than in ER(+) tumors. The highest tertile of IL-5 was more strongly associated with ER(-) (OR = 2.33, 95 % CI 1.40-3.90) and TNBCs (OR = 2.78, 95 % CI 1.53-5.06) compared to ER(+) and LumA cancers, respectively, particularly among premenopausal women (OR = 4.17, 95 % CI 1.86-9.34, ER(-) vs. ER(+); OR = 5.60, 95 % CI 2.09-15.01, TNBC vs. LumA). Elevated Th1 cytokines were also detected in women with ER(-) and TNBCs, with women in the highest tertile of interferon α2 (OR = 2.39, 95 % CI 1.31-4.35) or tumor necrosis factor-α (OR = 2.27, 95 % CI 1.21-4.26) being twice as likely to have TNBC versus LumA cancer. When cytokine ratios were examined, women with the highest ratios of Th1 cytokines to IL-5 levels were least likely to have ER(-) or TNBCs compared to ER(+) or LumA cancers, respectively. The strongest associations were in premenopausal women, who were up to 80 % less likely to have TNBC than LumA cancers (IL-12p40/IL-5, OR = 0.19, 95 % CI 0.07-0.56). These findings indicate that immune function is associated with ER(-) and TNBC and may be most relevant among younger women, who are likely to be diagnosed with these aggressive phenotypes.