Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study.

IMPORTANCE: There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. OBJECTIVE: To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. DESIGN, SETTING, AND PARTICIPANTS: The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. MAIN OUTCOMES AND MEASURES: Primary outcomes are breast cancer recurrence, second primary cancer, and death. RESULTS: Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer-specific survival and invasive disease-free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer-specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease-free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). CONCLUSIONS AND RELEVANCE: Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.

Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study.

IMPORTANCE: Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. OBJECTIVE: To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. DESIGN, SETTING, AND PARTICIPANTS: In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. EXPOSURES: Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. MAIN OUTCOMES AND MEASURES: Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. RESULTS: A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.03-0.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. CONCLUSIONS AND RELEVANCE: CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy. Oncologists should consider discussing CAM with their patients during the chemotherapy decision-making process.

Use of Chinese medicine among foreign-born Chinese residents of San Francisco.

OBJECTIVES: To explore the utilization patterns and attitudes toward Chinese medicine (CM) among foreign-born Chinese residents of San Francisco. METHODS: A cross-sectional survey using convenience sampling was conducted at 11 community organizations at San Francisco over a 2-month period. RESULTS: Among 244 participants using any healthcare services in the 2 years prior, 195 (80%) reported using CM. Over 90% of the CM users reported visiting conventional medical providers in the same period. Use of CM was significantly associated with recent immigration, origination from mainland China, lack of insurance, high school graduation, and marital status. Frequently used CM modalities included herbal prescriptions (52%) and over-the-counter herbal pills (44%). Half (48.2%) of the CM users reported using multiple CM modalities, and a third (35.9%) reported regular CM visits over the past 6 months. Of CM users, 36% reported informing physicians of their CM use. Of CM users that did not inform physicians of CM use, half (48.4%) indicated willingness to openly discuss the topic with their healthcare providers. CONCLUSIONS: CM utilization is common among foreign-born Chinese residents of San Francisco. Many use conventional treatments and CM concurrently, but few inform their physicians of CM use. Foreign-born Chinese patients may be better served if physicians better recognized and understood their medical needs, treatment preferences and practices.

Changes in vitamin and mineral supplement use after breast cancer diagnosis in the Pathways Study: a prospective cohort study.

BACKGROUND: Vitamin and mineral supplement use after a breast cancer diagnosis is common and controversial. Dosages used and the timing of initiation and/or discontinuation of supplements have not been clearly described. METHODS: We prospectively examined changes in use of 17 vitamin/mineral supplements in the first six months following breast cancer diagnosis among 2,596 members (28% non-white) of Kaiser Permanente Northern California. We used multivariable logistic regression to examine demographic, clinical, and lifestyle predictors of initiation and discontinuation. RESULTS: Most women used vitamin/mineral supplements before (84%) and after (82%) diagnosis, with average doses far in excess of Institute of Medicine reference intakes. Over half (60.2%) reported initiating a vitamin/mineral following diagnosis, 46.3% discontinuing a vitamin/mineral, 65.6% using a vitamin/mineral continuously, and only 7.2% not using any vitamin/mineral supplement before or after diagnosis. The most commonly initiated supplements were calcium (38.2%), vitamin D (32.01%), vitamin B6 (12.3%) and magnesium (11.31%); the most commonly discontinued supplements were multivitamins (17.14%), vitamin C (15.97%) and vitamin E (45.62%). Higher education, higher intake of fruits/vegetables, and receipt of chemotherapy were associated with initiation (p-values <0.05). Younger age and breast-conserving surgery were associated with discontinuation (p-values <0.05). CONCLUSIONS: In this large cohort of ethnically diverse breast cancer patients, high numbers of women used vitamin/mineral supplements in the 6 months following breast cancer diagnosis, often at high doses and in combination with other supplements. The immediate period after diagnosis is a critical time for clinicians to counsel women on supplement use.

A comprehensive review of opioid-induced hyperalgesia.

Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.

Evaluation of sacroiliac joint interventions: a systematic appraisal of the literature.

BACKGROUND: The sacroiliac joint has been implicated as a source of low back and lower extremity pain. There are no definite historical, physical, or radiological features that can definitively establish a diagnosis of sacroiliac joint pain. Based on the present knowledge, an accurate diagnosis is made only by controlled sacroiliac joint diagnostic blocks. The sacroiliac joint has been shown to be a source of pain in 10% to 27% of suspected patients with chronic low back pain utilizing controlled comparative local anesthetic blocks. STUDY DESIGN: A systematic review of diagnostic and therapeutic sacroiliac joint interventions. OBJECTIVE: To evaluate the accuracy of diagnostic sacroiliac joint interventions and the utility of therapeutic sacroiliac joint interventions. METHODS: The literature search was carried out by searching the databases of PubMed, EMBASE, and Cochrane reviews. Methodologic quality assessment of included studies was performed using the Agency for Healthcare Research and Quality (AHRQ) methodologic quality criteria for diagnostic accuracy and observational studies, whereas randomized trials were evaluated utilizing the Cochrane review criteria. Only studies with scores of 50 or higher were included for assessment. Level of evidence was based on the U.S. Preventive Services Task Force (USPSTF) criteria. OUTCOME MEASURES: For diagnostic interventions, the outcome criteria included at least 50% pain relief coupled with a patient's ability to perform previously painful maneuvers with sustained relief using placebo-controlled or comparative local anesthetic blocks. For therapeutic purposes, outcomes included significant pain relief and improvement in function and other parameters. Short-term relief for therapeutic interventions was defined as 6 months or less, whereas long-term effectiveness was defined as greater than 6 months. RESULTS: The indicated level of evidence is II-2 for the diagnosis of sacroiliac joint pain utilizing comparative, controlled local anesthetic blocks. The prevalence of sacroiliac joint pain is estimated to range between 10% and 38% using a double block paradigm in the study population. The false-positive rate of single, uncontrolled, sacroiliac joint injections is 20% to 54%. The evidence for provocative testing to diagnose sacroiliac joint pain is Level II-3 or limited. For radiofrequency neurotomy the indicated evidence is limited (Level II-3) for short- and long-term relief. LIMITATIONS: The limitations of this systematic review include the paucity of literature evaluating the role of both diagnostic and therapeutic interventions and widespread methodological flaws. CONCLUSIONS: The indicated evidence for the validity of diagnostic sacroiliac joint injections is Level II-2. The evidence for the accuracy of provocative maneuvers in the diagnosing of sacroiliac joint pain is limited (Level II-3). The evidence for radiofrequency neurotomy is also limited (Level II-3).

Systematic assessment of diagnostic accuracy and therapeutic utility of lumbar facet joint interventions.

BACKGROUND: Lumbar facet joints are a well recognized source of low back pain and referred pain in the lower extremity in patients with chronic low back pain. Conventional clinical features and other non-invasive diagnostic modalities are unreliable in diagnosing lumbar zygapophysial joint pain. Controlled diagnostic studies have shown the prevalence of lumbar facet joint pain in 27% to 40% of the patients with chronic low back pain without disc displacement or radiculitis, with a false-positive rate of 27% to 47% with a single diagnostic block. STUDY DESIGN: A systematic review of diagnostic and therapeutic lumbar facet joint interventions. OBJECTIVE: To determine the clinical utility of diagnostic and therapeutic lumbar facet joint interventions in managing chronic low back pain of facet joint origin. METHODS: Review of the literature for clinical studies on efficacy and utility of facet joint interventions in diagnosing and managing facet joint pain was performed according to the Agency for Healthcare Research and Quality (AHRQ) criteria for diagnostic studies and observational studies and the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials. Data sources included relevant literature of the English language identified through searches of Medline and EMBASE from 1966 to December 2008 and manual searches of bibliographies of known primary and review articles. Analysis results were performed for diagnostic and therapeutic interventions separately. LEVEL OF EVIDENCE: The level of evidence was defined as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF) for therapeutic interventions. OUTCOME MEASURES: For diagnostic interventions, studies must have been performed utilizing controlled local anesthetic blocks. Pain relief was categorized as at least 80% pain relief from baseline pain and ability to perform previously painful movements. For therapeutic interventions, the primary outcome measure was pain relief with secondary outcome measures of improvement in functional status, psychological status, return to work, and reduction in opioid intake. For therapeutic interventions, short-term pain relief was defined as relief lasting 6 months or less and long-term relief as longer than 6 months. RESULTS: Based on USPSTF criteria, evidence showed Level I or II-1 for diagnostic facet joint nerve blocks. Based on the review of included therapeutic studies, Level II-1 to II-2 evidence was indicated for lumbar facet joint nerve blocks with indicated level of evidence of Level II-2 to II-3 for lumbar radiofrequency neurotomy. LIMITATIONS: The shortcoming of this systematic review of lumbar facet joint interventions is the paucity of published literature. CONCLUSION: The evidence for diagnosis of lumbar facet joint pain with controlled local anesthetic blocks is Level I or II-1. The indicated level of evidence for therapeutic lumbar facet joint interventions is Level II-1 or II-2 for lumbar facet joint nerve blocks, Level II-2 or II-3 evidence for radiofrequency neurotomy, and Level III (limited) evidence for intraarticular injections.

Complementary and alternative therapy use before and after breast cancer diagnosis: the Pathways Study.

Many women use complementary and alternative medicine (CAM) to maintain or improve their health. We describe CAM use among the first 1,000 participants enrolled in the Pathways Study, an ongoing prospective cohort study of women diagnosed with breast cancer (BC). Participants, identified by rapid case ascertainment in Kaiser Permanente Northern California, are women > or = 21 years diagnosed with first invasive BC. Comprehensive baseline data are collected on CAM use through in-person interviews. Study participants include 70.9% non-Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African-Americans, and 3.4% others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (+/-SD) age 59.5 (+/-12.0) years and reported prior use of at least one form of CAM (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at least weekly by >20% of women included green tea, glucosamine, omega-3 fatty acids, prayer and religion. CAM use was high (86.1% of participants) in the period immediately following diagnosis; 47.5% used botanical supplements, 47.2% used other natural products, 28.8% used special diets, 64.2% used mind-body healing, and 26.5% used body/energy/other treatments. In multivariable analyses, frequent use of each CAM modality before and after diagnosis was associated with use of other CAM modalities and other health behaviors (i.e., high fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is common in this diverse group of women. Our results emphasize the need for clinicians to discuss CAM use with all BC patients.

Dietary patterns using Traditional Chinese Medicine principles in epidemiological studies.

Dietary intake and nutritional factors have been shown to be associated with many chronic diseases, such as heart disease, obesity, diabetes, and cancer. There are many approaches to studying dietary intake in relationship to disease; each approach has its strengths and weaknesses. Examples of different methods of studying dietary patterns will be reviewed. In most cultures, consumed and preferred foods are based on cultural and societal influence. Thus, it is important to consider dietary patterns within the context of culture in addition to the standard nutrients or food groupings approach. Traditional Chinese Medicine (TCM) offers another dimension to food analysis. Our approach classifies dietary intake based on Traditional Chinese Medicine principles of yin and yang, hot and cold, and acidic and alkaline forming food concepts in a case-control study of dietary factors and breast cancer. Our results complement previously reported findings of an increased risk of breast cancer associated with dietary fats in Taiwanese women. Our discussion will focus on the implication of using this dietary pattern research and the challenge of combining this research with culturally sensitive messages to improve health. Our ultimate goal is to design an intervention strategy for disease prevention and health promotion that is culturally appropriate for specific populations.

The Pathways Study: a prospective study of breast cancer survivorship within Kaiser Permanente Northern California.

OBJECTIVE: With 2.3 million breast cancer survivors in the US today, identification of modifiable factors associated with breast cancer recurrence and survival is increasingly important. Only recently new studies have been designed to examine the impact of lifestyle factors on prognosis, including Pathways, a prospective study of women with breast cancer in Kaiser Permanente Northern California (KPNC). METHODS: Pathways aims to examine the effect on recurrence and survival of (1) lifestyle factors such as diet, physical activity, quality of life, and use of alternative therapies and (2) molecular factors such as genetic polymorphisms involved in metabolism of chemotherapeutic agents. Eligibility includes any woman diagnosed with invasive breast cancer within KPNC, no previous diagnosis of other invasive cancer, age 21 years or older, and ability to speak English, Spanish, Cantonese, or Mandarin. Newly diagnosed patients are identified daily from electronic pathology records and are enrolled within two months of diagnosis. An extensive baseline interview is conducted, blood and saliva samples are collected, and body measurements are taken. Women are followed for lifestyle updates, treatment, and outcomes by self-report and query of KPNC databases. RESULTS: Recruitment began in 9 January, 2006, and as of 16 January, 2008, 1,539 women have been enrolled along with collection of 1,323 blood samples (86%) and 1,398 saliva samples (91%). CONCLUSIONS: The Pathways Study will become a rich resource to examine behavioral and molecular factors and breast cancer prognosis.

Developing and validating a measure of Chinese cultural views of health and cancer.

To develop and validate quantitative scales that measure Chinese cultural views about health and cancer, cultural views were assessed by a 30-item scale through telephone interviews with 438 Chinese-American women aged 50 and older. Cultural subscales were identified using principal component analysis and validated by their associations with age at immigration and breast, cervical, and colorectal cancer (CRC) screening patterns. The overall scale had good reliability (Cronbach's alpha = .79). Factor analysis yielded seven cultural subscales-fatalism, hot-cold balance, use of herbs, self-care, medical examination, lifestyle, and Western medicine (alpha = .39 to .82). The majority of the cultural subscales were significantly associated with age at immigration (p < .001). Fatalism, Self-Care, and Medical Examination subscales consistently predicted nonadherence to breast, cervical, and CRC screening recommendations, even after considering other factors. Chinese cultural views consist of at least seven domains and may influence older women's breast, cervical, and CRC screening.

Lifestyle factors and survival in women with breast cancer.

With increasing longevity and more effective cancer therapies, the population of cancer survivors is increasing. For example, it is estimated that there are over 2 million breast cancer survivors in the United States. Among cancer survivors and their families, there is substantial interest in whether there is anything that they can do beyond conventional therapy to improve their prognosis. Chief among these is interest in diet and use of complementary and alternative therapies. Despite this interest, there is surprisingly little that is known about the effects of these factors on cancer survival. This is in part because of the usual approach to research on diet and breast cancer in human populations. Studies that have had food and nutrition as a main interest have focused almost exclusively on cancer etiology and prevention; there are literally hundreds of such studies. Meanwhile, studies of populations after a breast cancer diagnosis have rarely considered lifestyle factors. Such studies have focused largely on therapeutics, such as effects of different chemotherapy regimens, or prognostic factors, such as the effects of stage of disease, hormone receptor status, or gene expression signatures on prognosis. To the extent that lifestyle factors have been a focus of cancer prognosis studies, they have often been aimed at the question of whether they impact quality of life, and not on whether they influence cancer survival or recurrence. There have been a handful of studies that have had lifestyle factors such as diet and physical activity as a principal focus. In addition to 2 randomized trials, the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living Study, there are at least 5 ongoing prospective cohort studies in breast cancer survivors that have diet as a main focus. Although these studies differ in various aspects, they are all aimed at examining whether differences in diet may result in differences in recurrence and mortality rates. One such study, the Pathways Study, is a prospective cohort study that began recruitment of study participants in early 2006. This study is unique in that it is enrolling women as soon after breast cancer diagnosis as is practical, whereas other studies have generally enrolled women after completion of adjuvant therapy or later. This and other studies promise to provide some of the first objective information regarding diet and breast cancer prognosis and serve as models for studies of diet and prognosis of other cancers.

Inverse association of antioxidant and phytoestrogen nutrient intake with adult glioma in the San Francisco Bay Area: a case-control study.

BACKGROUND: Increasing evidence from epidemiologic studies suggest that oxidative stress may play a role in adult glioma. In addition to dietary antioxidants, antioxidant and weak estrogenic properties of dietary phytoestrogens may attenuate oxidative stress. Our hypothesis is that long-term consumption of dietary antioxidants and phytoestrogens such as genistein, daidzein, biochanin A, formononetin, matairesinol, secoisolariciresinol and coumestrol, may reduce the risk of adult glioma. METHODS: Using unconditional logistic regression models, we compared quartiles of consumption for several specific antioxidants and phytoestrogens among 802 adult glioma cases and 846 controls from two study series from the San Francisco Bay Area Adult Glioma Study, 1991-2000, controlling for vitamin supplement usage, age, socioeconomic status, gender, ethnicity and total daily calories. For cases, dietary information was either self-reported or reported by a proxy. For controls, dietary information was self-reported. Gender- and series-specific quartiles of average daily nutrient intake, estimated from food-frequency questionnaires, were computed from controls. RESULTS: Significant p-values (trend test) were evaluated using significance levels of either 0.05 or 0.003 (the Bonferroni corrected significance level equivalent to 0.05 adjusting for 16 comparisons). For all cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.003), carotenoids (alpha- and beta-carotene combined, p < 0.05), daidzein (p = 0.003), matairesinol (p < 0.05), secoisolariciresinol (p < 0.003), and coumestrol (p < 0.003). For self-reported cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.05) and daidzein (p < 0.05). CONCLUSION: Our results support inverse associations of glioma with higher dietary antioxidant index and with higher intake of certain phytoestrogens, especially daidzein.

Reliability and validity of an assessment of usual phytoestrogen consumption (United States).

OBJECTIVE: To evaluate the reliability and validity of a food-frequency questionnaire (FFQ) and database designed to quantify phytoestrogen consumption. METHODS: This study included 195 members of the California Teachers Study (CTS) cohort who, over a 10-month period, completed four 24-h dietary recalls, a pre- and post-study FFQ, and provided two 24-h urine specimens. Participants (n = 106) in a parallel study (and 18 women who dropped out of the long-term study) completed a single recall and FFQ, and provided one 24-h urine specimen. Urinary phytoestrogens were determined using liquid chromatography-mass spectrometry. Reliability and validity were evaluated using Shrout-Fleiss intraclass correlations and energy-adjusted deattenuated Pearson correlations, respectively. RESULTS: Correlations reflecting the reproducibility of the FFQ phytoestrogen assessment ranged from 0.67 to 0.81. Validity correlations (FFQ compared to dietary recalls) ranged from 0.67 to 0.79 for the major phytoestrogenic compounds (i.e., daidzein, genistein, and secoisolariciresinol) and 0.43 to 0.54 for the less common compounds. Compared to urinary levels, validity correlations ranged from 0.41 to 0.55 for the isoflavones and 0.16 to 0.21 for total lignans. CONCLUSION: Our isoflavone assessment is reproducible, valid, and an excellent tool for evaluating the relationship with disease risk in non-Asian populations. Further research is needed before these tools can accurately be used to assess lignan consumption.

Breast cancer and dietary factors in Taiwanese women.

OBJECTIVES: To examine the effect of the consumption of dietary factors on the risk of breast cancer in a case-control study in Taiwan. METHODS: Two-hundred-and-fifty cases and 219 age-matched controls between the ages of 25 and 74 were interviewed in person between 1996 and 1999. Usual consumption of dietary habits including 100 foods was assessed using a food frequency questionnaire and a nutrient database developed and validated in Taiwanese populations. RESULTS: Cases consumed significantly more fat than controls. Cases also consumed statistically significant less supplements such as vitamins and mineral than controls. Food group analyses showed that highest quartile of beef and pork intake significantly increased risk in younger women (OR = 2.5, 95% CI = 1.0-6.0) and all women (OR = 2.5, 95% CI = 1.1-3.3). The age- education- and total calorie-adjusted odds ratio (OR) of breast cancer risk comparing the highest and second highest quartile of fat intake to the lowest quartile was 5.1, 95% confidence interval (CI): 2.1-13 and 3.5, 95% CI: 1.4-8.7 among those younger cases (< or =40). A multiple regression model indicates a protective effect of supplements (OR: 0.40, 95% CI: 0.3-07) and a harmful effect of dietary fat (OR: 2.6, 95% CI: 1.4-5.0) for the highest versus lowest quartile in all women. CONCLUSIONS: Our results indicate a strong protective effect of dietary supplements and a harmful effect of dietary fats on the risk of breast cancer among women in Taiwan. These findings should be confirmed in future follow-up studies. Specific amount of dietary supplements and dietary fats should be quantified for a more accurate evaluation on the risk for breast cancer in this population.

Phytoestrogen intake and endometrial cancer risk.

BACKGROUND: The development of endometrial cancer is largely related to prolonged exposure to unopposed estrogens. Phytoestrogens (i.e., weak estrogens found in plant foods) may have antiestrogenic effects. We evaluated the associations between dietary intake of seven specific compounds representing three classes of phytoestrogens (isoflavones, coumestans, and lignans) and the risk of endometrial cancer. METHODS: In a case-control study from the greater San Francisco Bay Area, we collected dietary information from 500 African American, Latina, and white women aged 35-79 years who were diagnosed with endometrial cancer between 1996 and 1999 and from 470 age- and ethnicity-matched control women identified through random-digit dialing. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Isoflavone (OR = 0.59, 95% CI = 0.37 to 0.93 for the highest versus lowest quartile of exposure) and lignan (OR = 0.68, 95% CI = 0.44 to 1.1) consumptions were inversely related to the risk of endometrial cancer. These associations were slightly stronger in postmenopausal women (OR = 0.44, 95% CI = 0.26 to 0.77 and OR = 0.57, 95% CI = 0.34 to 0.97 for isoflavones and lignans, respectively). Obese postmenopausal women consuming relatively low amounts of phytoestrogens had the highest risk of endometrial cancer (OR = 6.9, 95% CI = 3.3 to 14.5 compared with non-obese postmenopausal women consuming relatively high amounts of isoflavones); however, the interaction between obesity and phytoestrogen intake was not statistically significant. CONCLUSION: Some phytoestrogenic compounds, at the levels consumed in the typical American-style diet, are associated with reduced risk of endometrial cancer.

Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study.

Epidemiological and pathological data suggest that thyroid cancer may well be an estrogen-dependent disease. The relationship between thyroid cancer risk and dietary phytoestrogens, which can have both estrogenic and antiestrogenic properties, has not been previously studied. We present data from a multiethnic population-based case-control study of thyroid cancer conducted in the San Francisco Bay Area. Of 817 cases diagnosed between 1995 and 1998 (1992 and 1998 for Asian women), 608 (74%) were interviewed. Of 793 controls identified through random-digit dialing, 558 (70%) were interviewed. Phytoestrogen consumption was assessed via a food-frequency questionnaire and a newly developed nutrient database. The consumption of traditional and nontraditional soy-based foods and alfalfa sprouts were associated with reduced risk of thyroid cancer. Consumption of "western" foods with added soy flour or soy protein did not affect risk. Of the seven specific phytoestrogenic compounds examined, the isoflavones, daidzein and genistein [odds ratio (OR), 0.70; 95% confidence interval (CI), 0.44-1.1; and OR, 0.65, 95% CI, 0.41-1.0, for the highest versus lowest quintile of daidzein and genistein, respectively] and the lignan, secoisolariciresinol (OR, 0.56; 95% CI, 0.35-0.89, for the highest versus lowest quintile) were most strongly associated with risk reduction. Findings were similar for white and Asian women and for pre- and postmenopausal women. Our findings suggest that thyroid cancer prevention via dietary modification of soy and/or phytoestrogen intake in other forms may be possible but warrants further research at this time.