Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies.

BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.

A Coala-T-Cannabis Survey Study of breast cancer patients' use of cannabis before, during, and after treatment.

BACKGROUND: The goal of this study was to characterize cannabis use among patients with breast cancer, including their reasons for and timing of use, their sources of cannabis information and products, their satisfaction with the information found, their perceptions of its safety, and their dialogue about cannabis with their physicians. METHODS: United States-based members of the Breastcancer.org and Healthline.com communities with a self-reported diagnosis of breast cancer within 5 years (age ≥ 18 years) were invited to participate in an anonymous online survey. After informed consent was obtained, nonidentifiable data were collected and analyzed. RESULTS: Of all participants (n = 612), 42% (n = 257) reported using cannabis for relief of symptoms, which included pain (78%), insomnia (70%), anxiety (57%), stress (51%), and nausea/vomiting (46%). Furthermore, 49% of cannabis users believed that medical cannabis could be used to treat cancer itself. Of those taking cannabis, 79% had used it during treatment, which included systemic therapies, radiation, and surgery. At the same time, few (39%) had discussed it with any of their physicians. CONCLUSIONS: A significant percentage of survey participants (42%) used cannabis to address symptoms; approximately half of these participants believed that cannabis could treat cancer itself. Most participants used cannabis during active cancer treatment despite the potential for an adverse event during this vulnerable time. Furthermore, most participants believed that cannabis was safe and were unaware that product quality varied widely and depended on the source. This study reviews the research on medicinal cannabis in the setting of these findings to help physicians to recognize its risks and benefits for patients with cancer. LAY SUMMARY: Almost half of patients with breast cancer use cannabis, most commonly during active treatment to manage common symptoms and side effects: pain, anxiety, insomnia, and nausea. However, most patients do not discuss cannabis use with their physicians. Instead, the internet and family/friends are the most common sources of cannabis information. Furthermore, most participants believe that cannabis products are safe and are unaware that the safety of many products is untested.

Serum 25-hydroxyvitamin D concentrations and lung cancer risk in never-smoking postmenopausal women.

PURPOSE: Vitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations. METHODS: In the Women's Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers. Baseline serum 25(OH)D was assayed by a chemiluminescent method. Logistic regression was used to estimate odds ratios (ORs) for quartiles and predefined clinical cutoffs of serum 25(OH)D concentrations. RESULTS: Comparing quartiles 4 versus 1 of serum 25(OH)D concentrations, ORs were 1.06 [95% confidence interval (CI) 0.61-1.84] for all lung cancer, 0.94 (95% CI 0.52-1.69) for NSCLC, and 0.91 (95% CI 0.49-1.68) for adenocarcinoma. Comparing serum 25(OH)D ≥ 75 (high) versus <30 nmol/L (deficient), ORs were 0.76 (95% CI 0.31-1.84) for all lung cancer, 0.71 (95% CI 0.27-1.86) for NSCLC, and 0.81 (95% CI 0.31-2.14) for adenocarcinoma. There is suggestive evidence that CaD supplementation (1 g calcium + 400 IU D3/day) and a high level of circulating vitamin A may modify the associations of 25(OH)D with lung cancer overall and subtypes (p interaction <0.10). CONCLUSIONS: In this group of never-smoking postmenopausal women, the results did not support the hypothesis of an association between serum 25(OH)D and lung cancer risk.

Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies.

Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival.Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI).Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500-600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800-1,200 mg/d); HR (95% CI) was 1.07 (1.01-1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04-1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model.Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients.Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060-70. ©2017 AACR.

Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors.

BACKGROUND: The risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain. METHODS: The authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results-affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional-hazards models. RESULTS: Endometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence. CONCLUSIONS: In a community-based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen-associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association.

Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.

BACKGROUND: Clinical outcomes of the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial have been reported during 7.0 years of active intervention. We now report outcomes 4.9 years after the intervention stopped and cumulative findings. METHODS: Postmenopausal women (N=36,282) were randomized; postintervention follow-up continued among 29,862 (86%) of surviving participants. Primary outcomes were hip fracture and colorectal cancer. Breast cancer, all cancers, cardiovascular disease (CVD), and total mortality were predetermined major study outcomes. RESULTS: Hip fracture incidence was comparable in the supplement and the placebo groups, postintervention hazard ratio (HR)=0.95, 95% confidence interval (95% CI: 0.78, 1.15) and overall HR=0.91 (95% CI: 0.79, 1.05). Overall, colorectal cancer incidence did not differ between randomization groups, HR=0.95 (95% CI: 0.80, 1.13). Throughout, there also was no difference in invasive breast cancer, CVD, and all-cause mortality between groups. In subgroup analyses, the invasive breast cancer effect varied by baseline vitamin D intake (p=0.03 for interaction). Women with vitamin D intakes >600 IU/d, had an increased risk of invasive breast cancer, HR=1.28 (95% CI; 1.03, 1.60). Over the entire study period, in post hoc analyses, the incidence of vertebral fractures, HR=0.87 (95% CI: 0.76, 0.98) and in situ breast cancers, HR=0.82 (95% CI: 0.68, 0.99) were lower among women randomized to supplementation. CONCLUSION: After an average of 11 years, calcium and vitamin D supplementation did not decrease hip fracture or colorectal cancer incidence. Exploratory analyses found lower vertebral fracture and in situ breast cancer incidence in the supplement users. There was no effect on CVD or all-cause mortality.

Nutrition and physical activity influence on breast cancer incidence and outcome.

INTRODUCTION AND AIMS: To provide a current perspective on nutrition and physical activity influence on breast cancer. METHODS AND RESULTS: A comprehensive literature review was conducted and selective presentation of findings follows. While some observational studies have associated higher dietary fat intake with higher breast cancer incidence, two full-scale randomized, clinical trials of dietary fat intake reduction programs were negative. However, a lifestyle intervention targeting fat intake reduction in the Women's Intervention Nutrition Study (WINS), resulted in weight loss and also reduced breast cancer recurrences in women with early stage disease. Observational studies evaluating specific nutrient intakes and dietary supplements have provided mixed results. Several observational studies find women with early stage breast cancer with lower 25-hydroxyvitamin D levels at higher recurrence risk, a finding requiring cautious interpretation. The lifestyle factor most strongly and consistently associated with both breast cancer incidence and breast cancer recurrence risk is physical activity. A meta-analyses of observational studies supports the concept that moderate recreational physical activity (about 3-4 h walking per week) may reduce breast cancer incidence and that women with early stage breast cancer who increased or maintain their physical activity may have lower recurrence risk as well. Feasibility of achieving increased physical activity and weight loss in women with early-stage breast cancer has been established. Two full-scale randomized clinical trials are evaluating weight loss/maintenance and increased physical activity in relation to recurrence risk in women with early-stage, resected breast cancer. DISCUSSION/CONCLUSIONS: Dietary intake may influence breast cancer but influence is difficult to separate from influence of body weight. A consistent body of observational study evidence suggests higher physical activity has favorable influence on breast cancer incidence and outcome. While awaiting definitive evidence from ongoing randomized trials, breast cancer patients can reasonably be counseled to avoid weight gain and reduce body weight if overweight or obese and increase or maintain a moderate level of physical activity.

Calcium plus vitamin D supplementation and joint symptoms in postmenopausal women in the women's health initiative randomized trial.

BACKGROUND: Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse. OBJECTIVE: To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Women's Health Initiative randomized, placebo-controlled, clinical trial. DESIGN: In post hoc analyses, the results of the Women's Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups. RESULTS: At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [P=0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P=0.02). CONCLUSIONS: Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms.

Vitamin D intake and lung cancer risk in the Women's Health Initiative.

BACKGROUND: Prior research suggests that vitamin D protects against lung cancer only among certain subgroups. OBJECTIVES: We investigated whether vitamin D intake was associated with lung cancer and explored whether vitamin A intake modified the association. DESIGN: Prospective cohort data from 128,779 postmenopausal women, including 1771 incident lung cancers in the Women's Health Initiative (Clinical Trials and Observational Study) 1993-2010, were analyzed. Twelve percent of women received active intervention (1 g Ca + 400 IU vitamin D3/d) in the Calcium/Vitamin D Trial. Baseline total intake included both dietary intake (from food-frequency questionnaires) and supplement intake (from bottle labels). HRs were estimated by Cox proportional hazard models. RESULTS: No significant association was observed overall. Among never smokers, a total vitamin D intake ≥400 IU/d was significantly associated with lower risks of lung cancer (HR: 0.37; 95% CI: 0.18, 0.77 for ≥800 compared with <100 IU/d; P-trend = 0.01). No significant effect modification of total vitamin A intake on the association between total vitamin D intake and lung cancer was found. However, the Calcium/Vitamin D Trial active intervention was significantly associated with a lower lung cancer risk only among women with a vitamin A intake <1000 µg/d retinol activity equivalents (HR: 0.69; 95% CI: 0.50, 0.96; P-interaction = 0.09). CONCLUSIONS: Vitamin D intake was associated with a lower lung cancer risk in never-smoking, postmenopausal women. Lower vitamin A intake may be important for a beneficial association of 1 g Ca + 400 IU vitamin D3 supplementation with lung cancer. This trial was registered at clinicaltrials.gov as NCT00000611.

Frequency of private spiritual activity and cardiovascular risk in postmenopausal women: the Women's Health Initiative.

PURPOSE: Spirituality has been associated with better cardiac autonomic balance, but its association with cardiovascular risk is not well studied. We examined whether more frequent private spiritual activity was associated with reduced cardiovascular risk in postmenopausal women enrolled in the Women's Health Initiative Observational Study. METHODS: Frequency of private spiritual activity (prayer, Bible reading, and meditation) was self-reported at year 5 of follow-up. Cardiovascular outcomes were centrally adjudicated, and cardiovascular risk was estimated from proportional hazards models. RESULTS: Final models included 43,708 women (mean age, 68.9 ± 7.3 years; median follow-up, 7.0 years) free of cardiac disease through year 5 of follow-up. In age-adjusted models, private spiritual activity was associated with increased cardiovascular risk (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.02-1.31 for weekly vs. never; HR, 1.25; 95% CI, 1.11-1.40 for daily vs. never). In multivariate models adjusted for demographics, lifestyle, risk factors, and psychosocial factors, such association remained significant only in the group with daily activity (HR, 1.16; 95% CI, 1.03-1.30). Subgroup analyses indicate this association may be driven by the presence of severe chronic diseases. CONCLUSIONS: Among aging women, higher frequency of private spiritual activity was associated with increased cardiovascular risk, likely reflecting a mobilization of spiritual resources to cope with aging and illness.

Vitamin D and breast cancer incidence and outcome.

Based on preclinical studies and early clinical observations, an association between vitamin D status and breast cancer incidence and outcome has been proposed. Against this background, information on vitamin D and breast cancer was reviewed with focused attention on emerging clinical studies in this area. Prospective cohort studies do not associate 25-hydroxyvitamin D levels with breast cancer incidence. While case-control studies of this question are positive, they may be confounded by reverse causality as 25- hydroxyvitamin D levels are influenced by breast cancer presence and stage. Studies of 25-hydroxyvitamin D and subsequent breast cancer recurrence provide mixed results but strongest associations were seen in analyses uncontrolled for prognostic variables, cancer therapy, BMI and physical activity. The one full-scale randomized, placebo-controlled trial evaluating calcium (1000 mg elemental calcium per day) and vitamin D supplementation (400 IU D3 per day) with 36,282 participants failed to demonstrate a supplement effect on lowering breast cancer incidence. Breast cancer patients not uncommonly have vitamin D deficiency but limited control populations in available reports preclude precise prevalence estimates. As breast cancer patients are at risk for bone loss and musculoskeletal complaints from cancer or associated therapies, monitoring 25-hydroxyvitamin D levels and vitamin D3 supplementation in moderate dose (1,000- 1,500 IU D3 per day) can be recommended with expectation of mainly bone benefit. In women with breast cancer, future vitamin D supplementation studies need to be appropriately designed and powered to provide definitive assessments. However, a full-scale randomized trial evaluating the influence of vitamin D supplementation on breast cancer recurrence is likely not feasible.

Vitamin D and calcium supplementation and one-year change in mammographic density in the women's health initiative calcium and vitamin D trial.

BACKGROUND: Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density. METHODS: We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women's Health Initiative hormone therapy (HT) and calcium and vitamin D (CaD) trials. Women were randomized to receive 1,000 mg/d of elemental calcium carbonate plus 400 IU/d of vitamin D(3) or placebo. RESULTS: After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% CI = 0.81-1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95% CI = 0.61-1.11) vs. 1.16 (95% CI = 0.92-1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥ 80% of study supplements, ratios were 0.67 (95% CI = 0.41-1.07) in women not assigned to HT and 1.07 (95% CI = 0.79-1.47) women assigned to HT. CONCLUSIONS: We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year. IMPACT: Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.

Bisphosphonates and breast cancer prevention.

Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with cancer therapy in early stage disease. In addition, adjuvant breast cancer trials evaluating the oral bisphosphonate clodronate suggested a reduction in cancer recurrence, but the findings were mixed, with 2 positive and 1 negative report. In the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 study, adding the intravenous bisphosphonate zoledronic acid to endocrine therapy in premenopausal breast cancer patients significantly prolonged disease-free survival versus endocrine therapy alone (hazard ratio = 0.68; p = 0.008) at 62 months, and reduced local, regional, and distant recurrences. Clinical trial findings from other adjuvant trials (Z-FAST, ZO-FAST), neoadjuvant studies, and studies involving disseminated tumor cells (DTCs) are generally supportive of the ABCSG-12 conclusion, and recent data from AZURE suggest the importance of menopausal status. Preclinical studies provide data on the mechanisms of action that could mediate bisphosphonate direct and indirect anti-cancer effects. Recently, several observational studies (2 cohort studies and 2 case-control analyses) have associated oral bisphosphonate use with a lower breast cancer incidence. Such reports require cautious interpretation because confounding by indication is an issue: bisphosphonates are prescribed for women with low bone mineral density, and women with low bone density are at decreased breast cancer risk.

Vitamin D and breast cancer: interpreting current evidence.

Preclinical investigations and selected clinical observational studies support an association between higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk. However, the recently updated report from the Institute of Medicine concluded that, for cancer and vitamin D, the evidence was 'inconsistent and insufficient to inform nutritional requirements'. Against this background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and breast cancer incidence and outcome were reviewed. Current evidence supports the pursuit of several research questions but not routine 25-hydroxyvitamin D monitoring and vitamin D supplementation to reduce breast cancer incidence or improve breast cancer outcome.

The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.

25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women.

INTRODUCTION: Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms. STUDY DESIGN: Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial. MAIN OUTCOME MEASURES: 25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling. RESULTS: The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R=0.29, p<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile. CONCLUSIONS: Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.

Prospective evaluation of two recruitment strategies for a randomized controlled cancer prevention trial.

PURPOSE: To evaluate two recruitment strategies used during the full-scale randomized, placebo-controlled Selenium and Vitamin E Cancer Prevention Trial (SELECT) at one clinical center. BACKGROUND: Recruitment of participants to cancer prevention trials is challenging and costly and more efficient methods are needed. METHODS: SELECT participants were males ≥60 years old who were solicited with two recruitment strategies. In the control strategy, potential participants, identified through purchased mailing lists, were sent a SELECT invitation letter. In the 'spouse' strategy, letters were sent to married postmenopausal women already participating in the Women's Health Initiative (WHI) at our clinical center asking them to provide an enclosed SELECT invitation letter (identical to the one in the control strategy) to the 'man in her life'. Our hypothesis was that SELECT recruitment of men would be enhanced by this indirect mailing to their spouses already participating in a similar program. RESULTS: In the control strategy, 183,315 invitation letters were mailed to 60,000 men; cumulative response was 2.16%; 600 men ultimately enrolled in SELECT (15.1% of respondents) for a mailing recruitment cost of $259 per participant. In the spouse strategy, 800 women participating in WHI clinical studies had husbands; of the 2214 invitation letters mailed to this group of women, cumulative response was 2.75%; 34 men ultimately enrolled in SELECT (55.7% of respondents) for a mailing recruitment cost of $59 per participant. LIMITATION: Process information on how invitation letters were handled in the spouse strategy was not collected. CONCLUSION: A direct mail recruitment strategy was successful in recruiting men to a cancer prevention trial. A recruitment strategy involving indirect mailing to married women participating in a similar research program in the same center did not increase initial response substantially, but a higher proportion of respondents ultimately entered the prevention trial.

Dietary vitamin D and calcium intake and mammographic density in postmenopausal women.

OBJECTIVE: Dietary intake of vitamin D and calcium may be related to risk of breast cancer, possibly by affecting mammographic density. However, the few studies that have evaluated the association between these nutrients and mammographic density in postmenopausal women have had inconsistent results. METHODS: We conducted a cross-sectional analysis in 808 participants of the Mammogram Density Ancillary Study of the Women's Health Initiative. Mammographic percent density was measured using baseline mammograms taken before randomization of participants in the intervention trials. Vitamin D and calcium intake was assessed with a validated food frequency questionnaire and an inventory of current supplement use, both completed at baseline. RESULTS: After adjustment for age, body mass index, regional solar irradiance, and other factors, we did not find a relationship between vitamin D or calcium intake and mammographic density. Mean mammographic percent densities in women reporting total vitamin D intakes of less than 100, 100 to 199, 200 to 399, 400 to 599, and 600 or greater IU/day were 5.8%, 10.4%, 6.2%, 3.8%, and 5.1%, respectively (P trend = 0.67). Results in women reporting a total calcium intake of less than 500, 500 to 749, 750 to 999, 1,000 to 1,199, and 1,200 or greater mg/day were 7.3%, 4.9%, 7.3%, 6.9%, and 7.11%, respectively (P trend = 0.51). We did not observe any effect modification by overall level of mammographic density or solar irradiance, but supplemental vitamin D use was associated with lower density in younger women (P interaction = 0.009). CONCLUSIONS: These findings do not support a relationship between dietary vitamin D or calcium intake and mammographic density in postmenopausal women. Additional studies should explore these associations in women of different ages and in relation to serum vitamin D levels.

Early breast and prostate cancer and clinical outcomes (fracture).

Osteoporosis is a skeletal disorder characterized by low bone mass that is associated with increased risk of fracture. Nearly 40% of the 12 million cancer survivors in the United States were diagnosed with breast and prostate cancer. Therapy for these two diseases is not uncommonly associated with bone loss related to hormone-ablative therapy. In women, this includes the use of endocrine therapies and chemotherapy-related premature menopause. In men, hormone-ablative therapies include gonadotropin-releasing hormone analogs and bilateral orchiectomy. Fracture risk assessment includes bone mineral density determination in appropriate populations and integration of findings with identified risk factors. Strategies to prevent and treat bone loss include nonpharmacologic and pharmacologic interventions. In the former case, regular weight-bearing and muscle-strengthening exercise is encouraged along with smoking cessation, modulation of alcohol consumption, and fall prevention. Supplementation with calcium and vitamin D decreases fracture risk in subgroups. Pharmacologic interventions include use of oral or intravenous bisphosphonates, selective estrogen receptor modulators, and calcitonin. Estrogen/menopause hormone therapies are not recommended for use in breast cancer survivors related to potential influence on recurrence. Strategies for management of bone loss in breast and prostate cancer are outlined by guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network.