African American breast cancer survivors experience poor cancer outcomes that may, in part, be remedied by healthy lifestyle choices. Few studies have evaluated the health and lifestyle behaviors of this population. The purpose of this study was to characterize the health and lifestyle habits of African American breast cancer survivors and evaluate the socio-demographic and medical correlates of these behaviors.A total of 470 African American breast cancer survivors (mean age = 54 years) participated in an online survey. All participants completed measures assessing medical and demographic characteristics, physical activity, and sedentary behavior. Chi-square tests for association, nonparametric tests, and logistic regression models were used to assess associations. All statistical tests were two sided.Almost half (47%) of the women met the current guidelines for physical activity, almost half (47%) were obese, and many reported having high blood pressure (53%) or diabetes (21%). The prevalence of high blood pressure, diabetes, and high cholesterol increased by age (P<0.001), and obese women had a higher prevalence of high blood pressure (63% vs. 44%) and diabetes (21% vs. 12%) than did non-obese women . Obese women participated in significantly fewer total minutes of physical activity per week (100 minutes/week) than did non-obese women . The number of comorbid conditions was associated with increased odds for physical inactivity (odds ratio = 1.40) and obesity (odds ratio = 2.22).Many African American breast cancer survivors had chronic conditions that may be exacerbated by poor lifestyle choices. Our results also provide evidence that healthy lifestyle interventions among obese African American breast cancer survivors are urgently needed. Scientific advancements in cancer treatment during the past 30 years have resulted in improvements in cancer-specific and overall survival rates PA is associated with several benefits throughout the cancer continuum, including improvements in cancer-related symptoms , functional status, body mass index (BMI), and mood Few studies have reported on the health behaviors of AA breast cancer survivors, despite their increased vulnerability to poor health outcomes. Studies that provide data on the health behaviors of these women may help identify the factors that contribute to poor outcomes in this population. Descriptive studies are a necessary first step in filling the void and documenting the health and well-being of AA breast cancer survivors. Therefore, the purpose of this study was to (a) characterize the health behaviors of a sample of AA breast cancer survivors, (b) determine whether these behaviors differ by age group or obesity status, and (c) identify the determinants of lifestyle behaviors in this population.AA breast cancer survivors aged 18–70 years were identified through Sisters Network, Inc., the largest AA breast cancer survivorship organization in the United States. These women were recruited via solicitation emails about our survey and via anonymous survey links on social media sites and Sisters Network blog sites between April and July 2012. All surveys were completed using Survey Monkey, a web-based platform that allows investigators to create surveys, perform routine updates, and manage survey responses. Participants were eliminated from the final analyses if they were not breast cancer survivors, were not AA, or reported being diagnosed at younger than 18 years. The project was approved by the Institutional Review Board at The University of Texas MD Anderson Cancer Center prior to data collection, and a consent form was included on the initial survey web page. The Institutional Review Board approved all procedures, including the development of the web-based survey and the use of a passive consent form, before the survey was administered.Guidelines for PA were assessed via a self-administered instrument designed for the Women’s Health Initiative Time spent watching television or videos was reported by participants separately for weekdays and weekend days during the previous week. Total television time was calculated as the sum of the time participants watched television on weekdays and weekend days. This measure has been shown to have reasonable reliability and validity for estimating television-viewing time in adults 2). BMI risk categories were created to distinguish non-obese women from obese women and healthy women from normal/overweight (BMI<30 kg/m2) and obese (BMI≥30.0 kg/m2) women.The study participants’ self-reported height and weight were used to compute their BMI. BMI was computed in a standard manner: weight in kilograms was divided by height in meters squared  that were self-reported.t tests. In the event that the distributions of the continuous variables were skewed or non-normal, we used a Wilcoxon rank-sum test to assess differences. Differences in categorical variables were assessed with a chi-square test of associations. We then used bivariate logistic regression models followed by multivariable forward stepwise logistic regression models to assess the associations of the medical and socio-demographic characteristics with the outcome variables . In the stepwise regression model, the variables were progressively entered into the model if their significance level was at least 0.2 and were allowed to stay in the model if the significance remained at least 0.1 after adjusting for other variables. We opted to use this procedure to find the best possible model that fit the data. Indicators in multivariable  models included age group, education, disease stage at diagnosis, years since diagnosis, smoking status, use of hormone replacement therapy, and income. In addition, PA and television viewing were included in models for obesity status and vice versa. The number of comorbid conditions was treated as a continuous variable in our models. Logistic regression models were reported in odds ratios (ORs) and 95% confidence intervals (CIs). These data were analyzed using the SAS Enterprise System version 4.2. All statistical tests were two-sided, and alpha <0.05 was considered statistically significant.Means and frequencies were used to characterize the study participants. Mean differences in continuous indicators were assessed with paired Of 760 people who initially visited the website, 525 visitors identified themselves as breast cancer survivors, and 307 completed the survey. The mean age of the survey participants was 54 years; the mean time since diagnosis was 7 years; and most participants were diagnosed with stage II disease. More than half had a least one comorbid condition, and half had high blood pressure. Fifty-three percent of the women report having high blood pressure, 28% had high cholesterol, and 21% had diabetes. Generally, younger women were married, were diagnosed at a later disease stage, and were more likely to have undergone chemotherapy . In addition, a higher proportion of women 60 years and older reported having high blood pressure, cholesterol, and diabetes than did younger participants . The highest proportion of participants with high blood pressure was observed in obese women, and the highest proportion of nonsmokers was observed in non-obese women . Likewise, the number of comorbid conditions increased proportionally with age, and obese women reported having more comorbid conditions than did non-obese women . The descriptive characteristics are reported in Self-reported television viewing and PA are reported in Bivariate associations among the medical, demographic, and lifestyle characteristics are reported in Bivariate analyses revealed that a larger number of comorbid conditions were significantly associated with not meeting the current guidelines for PA. Similarly, in bivariate analyses, a lower education level was significantly associated with not meeting the current guidelines for PA . In stepwise logistic regression models, the number of comorbid conditions was significantly associated with not meeting current guidelines for PA . In the stepwise model, women who completed high school  and those with some college  were less likely to meet the current guidelines for PA than were women who had graduate degrees.Socio-demographic and medical characteristics were not significantly associated with a television-viewing time of more than 2 hours per day in bivariate or multivariable models.The number of comorbid conditions and level of education were significantly associated with self-reported obesity in bivariate models . In stepwise logistic regression models, the number of comorbid conditions  was associated with increased risk for obesity, and women who were recently diagnosed  were more likely to be obese than were women who had been diagnosed 10 years prior to study enrollment.In this study, we found that almost half of the women were obese, did not meet the current guidelines for PA, and had comorbid conditions. Fewer than half watched television for more than 2 hours per day. Comorbid conditions were prevalent in older women and women who were obese. Interestingly, we observed few lifestyle differences between population subgroups, but obese women were less active than non-obese women. In addition, the number of comorbid conditions appeared to be an important correlate of being obese and not meeting the current guidelines for PA. Our preliminary data show that AA breast cancer survivors need lifestyle interventions to curb high rates of inactivity and obesity, particularly because they are often burdened by other comorbid conditions that render them vulnerable to inactivity and obesity.Approximately 50% of the women in our study reported having high blood pressure, and another 20% and 30% reported having diabetes or high cholesterol levels, respectively, and these rates appeared to increase with age. The rates of high blood pressure and diabetes observed among the women in our study are similar to those reported in other studies of minority women Nearly half the women in our study were obese. These rates of obesity are comparable to those reported in previous studies of AA breast cancer survivors Our data indicate that 53% of the women in our study did not meet the current guidelines for PA and that 43% of them watched television for more than 2 hours per day. The percentage of women who did not meet the current guidelines for PA was similar to the percentage of healthy AA women not meeting PA guidelines The correlates of PA and SB in AA cancer survivors are not well understood. Herein, we found that education and comorbid conditions were significantly associated with PA, but we did not find any correlates for SB. AA breast cancer survivors reported similar levels of SB regardless of age, education, or health status. Alternatively, psychosocial constructs may be better correlates of PA and SB than demographic and medical conditions. Research assessing these correlates among AA breast cancer survivors is greatly needed.The results from this study provide important and unique information about a minority group of breast cancer survivors and the lifestyle characteristics of this population. There are, however, several limitations of this study that should be noted. Our study focused exclusively on AA breast cancer survivors and adding a comparison group  may have helped to rule out the potential for confounding. The sample of AA breast cancer survivors was relatively healthy and well educated, so the results may not be generalizable to other populations of AA breast cancer survivors. In addition, PA and SB were assessed using a self-reported measure; therefore, recall and reporting biases might have existed. Moreover, these data are cross-sectional and do not imply causal inference. Nonetheless, to our knowledge, this is one of the first studies to report on the sedentary habits of AA breast cancer survivors. Future studies should consider including a comparison condition to examine potential similarities and differences in study outcomes.In conclusion, these data show that many AA breast cancer survivors are overweight and obese, have comorbid conditions that may increase their risk for premature mortality, and are physically inactive. AA breast cancer survivors urgently need interventions that shield them from high rates of obesity and comorbid conditions. Ideally, these interventions will be based on their personal preferences and promote lifelong skills that enable them to adopt and maintain a physically active lifestyle. Researchers or institutions who partner with local and national organizations such as the Sisters Network may be able to harness the support needed to develop interventions in which minority breast cancer survivors are receptive to participating. Intervention studies may help to improve survival outcomes in this population.


Breast cancer is frequently a hormonally dependent cancer, and associations of circulating estrogens and androgens with subsequent breast cancer risk are well established in postmenopausal women. Associations of serum estrogens and androgens with breast cancer risk in premenopausal women are less well studied. The objective of this study was to determine whether estradiol and testosterone levels in serum collected before menopause are associated with subsequent breast cancer risk.in situ or invasive breast cancer cases with prediagnostic serum collected before menopause was matched to two controls by age, date, menstrual cycle day, and time of day of blood collection. Estradiol and testosterone concentrations were quantified by using specific radioimmunoassays, and sex hormone-binding globulin (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of the non-SHBG bound hormone fractions. Data were analyzed by using conditional logistic regression. All tests of statistical significance were two-sided.We conducted a prospective case-control study of 266 participants who were registered in the Columbia, Missouri, Serum Bank and not using exogenous hormones at the time of blood collection. Each of 98 Ptrend = 0.006). Comparable ORs for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0, 1.7 , 1.7 , and 4.2 . Total and non-SHBG-bound estradiol were not associated with breast cancer, but extreme variation in levels across the menstrual cycle coupled with relatively small numbers, particularly for analyses stratified by cycle phase, limited the power to detect associations.Serum testosterone was strongly and significantly associated with breast cancer risk. The relative odds (OR) for increasing quartiles of total testosterone were 1.0, 2.1  0.9 to 4.8), 1.5 , and 3.3 (95% CI, 1.5 to 7.5, Results suggest that premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer. Most breast tumors are estrogen dependent, and postmenopausal women with elevated serum estrogens are at an increased risk of developing breast cancer . EstrogeThe Columbia, MO, Serum Bank initially was established in 1977 as part of the National Cancer Institute (NCI) Biological Markers Project to identify serum markers for breast cancer. Participants were volunteers identified primarily through the Breast Cancer Detection Demonstration Project (BCDDP) at the University of Missouri Hospital and Ellis Fischel Cancer Center in Columbia. A total of 6,915 women who initially were free of cancer, other than nonmelanoma skin cancer, donated blood to the bank on one or more occasions between December 1977 and June 1989. All women gave written informed consent before donating serum to the serum bank, and Institutional Review Boards at the National Cancer Institute and Fox Chase Cancer Center approved the research reported herein.Serum specimens were collected, and clinical data, including age, height, weight, menstrual and reproductive histories, smoking, hormone replacement and oral contraceptive use, and family history of breast cancer, were obtained by self-report or medical-record review. Approximately 30 ml of blood was collected from each woman by using standard procedures. Blood was allowed to stand at room temperature for at least one-half hour or until it was thoroughly clotted and then refrigerated. Within 2 hours of collection, blood was centrifuged, and serum was separated and aliquoted into 1.1-ml sterile glass vials. Vials were labeled, sealed with rubber stoppers, and stored at -70°C.Follow-up of women who donated blood to the Columbia, MO, Serum Bank was conducted in two phases. Initial follow-up continued for up to 12 years until December 1989. A questionnaire was mailed to participants annually to ascertain information on interim cancer diagnoses. Women who indicated that they had a breast biopsy or breast cancer were sent a consent form for permission to obtain medical records, including pathology reports. For cancers at sites other than the breast, date of diagnosis was ascertained. An extended follow-up of Columbia, MO, Serum Bank participants was conducted by NCI in 1999 through 2004. Cancer diagnoses were ascertained by self-report and by searching the Missouri Cancer Registry, BCDDP Cohort files, and National Death Index (NDI) Plus. Of the 6,720 women included in the extended follow-up because they had one or more vials of serum remaining, 6,131 (91%) were located as either alive or dead, 589 (9%) were not able to be located, 59 (< 1%) refused to participate, and 49 (< 1%) were too ill to participate. In total, 1,751 women (25%) were identified as deceased, with confirmation of causes of death provided via NDI.in situ or invasive breast cancer that was confirmed by medical records, the Missouri Cancer Registry, or NDI. Initially, potential cases were selected if less than 1 year had elapsed since their last menses, or if they were younger than 50 years  at blood collection and missing data on the date of their last menses. For each of 117 potential cases that were identified, two potential controls who were alive at the age of the case diagnosis and who remained cancer free were randomly selected. Controls were matched to the case on age (± 2 years), date (± 1 year), menstrual cycle day , and time of day (± 2 hours) of blood collection. Matching criteria were relaxed to identify potential controls in some instances (age (n = 6), date (n = 11), cycle day (n = 13), and time (n = 5)). Final determination of menopausal status for potential participants who were missing data on the date of their last menses was based on age at blood collection and serum follicle-stimulating hormone (FSH) and estradiol concentrations. Those who were younger than 44 years  were presumed to be premenopausal, whereas those who were 45 to 49 years old and had an FSH greater than 25 mIU/ml and estradiol less than 25 pg/ml were considered to be postmenopausal and excluded from analysis. After exclusion of postmenopausal women and one control with serum testosterone of 102.5 ng/dl, 98 cases and 168 matched controls remained and were included in analyses.Cases for the current study included premenopausal women in the Columbia, MO, Serum Bank who were free of cancer other than nonmelanoma skin cancer and not taking exogenous estrogens or progestins at the time they donated blood, who subsequently were diagnosed with All laboratory analyses were performed at the Reproductive Endocrine Research Laboratory, University of Southern California Keck School of Medicine. Sera from each case and the matched control were grouped together, and matched sets were randomly organized within batches. The laboratory was blinded to which samples were from cases and which were from controls. Estradiol and testosterone were quantified by specific radioimmunoassays after organic solvent extraction and Celite column-partition chromatography, as described previously ,9. Sex hP less than 0.05 was used to determine statistical significance. All analyses were performed by using SAS 9.2  and STATA10.1 .The association of serum estradiol and testosterone with breast cancer risk for matched sets was evaluated by using conditional logistic regression. Univariate associations of individual characteristics shown in Table P = 0.08). More cases had a history of breast cancer in a first-degree relative compared with controls . Data on date of last menses were missing for 14.3% of cases and 11.3% of controls, and 9.2% of cases and 7.7% of controls had blood collected 34 or more days after their last menses. The median number of days from last menses at blood collection for these participants was 52 days . Cases' mean (± SD) age at breast cancer diagnosis was 58.7 ± 8.4 years . The mean (± SD) time from blood collection to diagnosis was 14.0 ± 6.6 years. Eighty-six tumors (88%) were invasive.Participant characteristics are summarized in Table P = 0.005) and bioavailable testosterone  concentrations than did controls. Total and bioavailable estradiol concentrations did not differ between the groups. Breast cancer risk also was not associated with total or bioavailable estradiol levels overall or in analyses stratified by menstrual cycle phase (Table Ptrend = 0.002). Results were not substantially different when analysis was restricted to women who were within 33 days of last menses at the time of blood collection.As shown in Table se Table . In contse Table . The assn = 86), results did not differ materially from those for all cases. However, a pattern of increasing risk with increasing total estradiol concentration in the follicular phase of the menstrual cycle emerged that was not apparent previously. Adjusted ORs for invasive breast cancer with increasing tertiles of follicular-phase total estradiol were 1.0, 1.8, and 2.0 , but the test for trend remained nonsignificant (Ptrend = 0.40). In contrast, associations of follicular-phase bioavailable estradiol with invasive cancer remained erratic, with adjusted ORs decreasing to 0.7  and then increasing to 3.2  across increasing tertiles of concentration.When we restricted analysis to invasive breast cancer (Ptrend = 0.03). Comparable ORs for non-SHBG-bound testosterone were 1.0, 1.6, 1.3, and 3.6 . Adjustment for MIS did not materially change results for total estradiol or non-SHBG-bound estradiol. Tests for interaction between MIS and total or bioavailable estradiol and testosterone in relation to breast cancer risk were not statistically significant.We previously showed a strong positive association of serum müllerian-inhibiting substance (MIS) with breast cancer risk. Adjustment for MIS attenuated only slightly the associations of total and non-SHBG-bound testosterone with breast cancer risk. In analysis adjusted for MIS in addition to other covariates, ORs for increasing quartiles of total testosterone were 1.0, 2.1, 1.2, and 3.0  and for bioavailable testosterone were 1.0, 2.1, 2.1, and 7.1 . Few cases (n = 31) were younger than 55 years old at diagnosis, and results are not shown for this subgroup.Because we did not have data on eventual age at menopause, we could not perform an analysis stratified by menopausal status at diagnosis. We, therefore, performed analysis limited to the 67 cases who were 55 years or older at diagnosis and their matched controls as a proxy for postmenopausal status at diagnosis. Serum total and bioavailable testosterone remained significantly associated with breast cancer risk in these analyses. Covariate adjusted ORs for increasing quartiles of total testosterone were 1.0, 2.4, 1.6, and 4.5 . For non-SHBG-bound testosterone, comparable ORs were 1.0, 2.1, 2.3, and 6.2 .The time from blood collection to diagnosis ranged from 2 months to 23 years. To evaluate the potential for reverse causality as an explanation for the observed association between serum testosterone and breast cancer risk, we repeated analyses restricted to cases whose blood was collected longer in time before diagnosis. Results were similar to those shown in Table The positive associations that we observed in the Columbia, MO, cohort between premenopausal serum testosterone levels and breast cancer risk are consistent with those reported previously in prospective studies. In the study of Hormones and Diet in the Etiology of Breast Tumors (ORDET) , the breThe association of premenopausal serum estradiol with breast cancer risk is less clear. Similar to our results, premenopausal serum estradiol was not associated with risk in EPIC  or in thElevated testosterone levels in serum collected before menopause remained associated with an increased risk of breast cancer in analyses limited to cases who were 55 years and older and presumably postmenopausal at diagnosis. We previously reported a significant increased risk of breast cancer among postmenopausal women with elevated testosterone levels in the Columbia, MO, cohort , and a pThe association of serum testosterone with breast cancer has been reported to be stronger for estrogen receptor-positive versus -negative tumors ,24,25, aWe previously observed a positive association of serum MIS with breast cancer risk in our study participants . BecauseOur study had several strengths. Most notably, hormones were measured in serum that was collected many years before the cases' breast cancer diagnoses, and cohort follow-up was 91% complete. It also had several potential limitations. Menstrual cycle day of blood collection was calculated as days since the last menses, even though days until the next menses more accurately estimate the cycle day. This is particularly of concern for estradiol, because of its large fluctuations across the menstrual cycle and may have contributed to lack of an apparent association of estradiol with breast cancer risk. Our relatively small sample size, particularly for stratified analyses, also limited the power to detect associations.Results suggest that premenopausal women with elevated serum total and non-SHBG-bound testosterone levels are at an increased risk of subsequent breast cancer.BCDDP: Breast Cancer Detection Demonstration Project; BMI: body mass index; CI: confidence interval; DHEA: dehydroepiandrosterone; EPIC: European Prospective Investigation into Cancer and Nutrition; FSH: follicle-stimulating hormone; MIS: müllerian-inhibiting substance; MO: Missouri; NCI: National Cancer Institute; NDI: National Death Index; NHS-II: Nurses' Health Study II; OR: odds ratio; ORDET: Hormones and Diet in the Etiology of Breast Tumors; SHBG: sex hormone-binding globulin.The authors declare that they have no competing interests.JFD participated in the design of the study, performed the statistical analysis, and contributed to manuscript preparation. FZS performed serum hormone analyses and contributed to manuscript preparation. LLK participated in the design of the study and case-control identification. LAB participated in the design of the study and manuscript preparation. All authors read and approved the final manuscript.


Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent. Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D (25(OH)D) are considered the best measure of vitamin D status.We conducted a prospective nested case-control study within the Nurses' Health Study II (NHSII). Plasma samples collected in 1996 to 1999 were assayed for 25(OH)D in 613 cases, diagnosed after blood collection and before 1 June 2007, and in 1,218 matched controls. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for several breast cancer risk factors.P-value, test for trend = 0.32). Results were similar when season-specific quartile cut points were used. Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis. Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors . The association did not vary by age at blood collection or season of blood collection, but did vary when stratified by body mass index .No significant association was observed between plasma 25(OH)D levels and breast cancer risk , Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population. However, although 1,25(OH)2D binds to VDR with 1,000 times the affinity of 25(OH)D, the latter is more abundant suggesting its interaction with VDR may not be trivial [2D is produced and used locally [2D is tightly regulated to maintain calcium homeostasis, while 25(OH)D serves as a pool for biologically active vitamin D and thus is a marker of overall vitamin D status [Vitamin D is an essential component of the endocrine system, responsible for calcium level maintenance, and is hypothesized to be involved in many other body systems. There are two circulating forms of vitamin D: 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D locally . 1,25ll lines -11. In all lines -14. In aromatase . Althougromatase -19.n = 100 cases) in which plasma 25(OH)D levels measured during pregnancy were not significantly associated with subsequent breast cancer ) [Vitamin D, which is hydroxylated in the liver into 25(OH)D, comes from dietary and supplement intake as well as sun exposure. Although several studies have assessed sun exposure and dietary intake separately, plasma levels of 25(OH)D are considered a better marker of vitamin D status because they incorporate all sources of exposure as well as skin color, weight, and other factors that influence an individual's vitamin D levels . The assThe NHSII was established in 1989, when 116,430 female registered nurses, aged 25 to 42 years, completed and returned a questionnaire. The cohort has been followed biennially by questionnaire to update exposures and ascertain newly diagnosed disease.Between 1996 and 1999, 29,611 cohort members, who were cancer-free and between the ages of 32 and 54 years, provided blood and urine samples. These women were similar to the overall cohort with respect to lifestyle factors, such as body mass index, parity, age at menarche, past oral contraceptive use, and only differed slightly in the prevalence of family history of breast cancer  . Of the n = 415 invasive) were reported on biennial questionnaires and confirmed by medical record review (n = 582) or verbal confirmation by the nurse (n = 31). Given the 99% confirmation rate on medical record review, these latter cases were included. Information on invasiveness and hormone receptor status was abstracted from the medical record. Mean time from blood draw to diagnosis was 57 months (range = 1 to 127). Two controls were matched to each case  on age (± 2 years); menopausal status at diagnosis; month/year of collection (± 2 months); ethnicity ; luteal day  ± 1 day); and for each blood collection, time of day (± 2 hours) and fasting status .Breast cancer cases were identified on biennial questionnaires; the National Death Index was searched for non-responders. Cases had no previously reported cancer diagnosis and were diagnosed with breast cancer after blood collection but before 1 June 2007. Overall, 613 cases of breast cancer (25(OH)D was assayed at Heartland Assays, Inc.  using a radioimmunoassay with radioiodinated tracers after acetonitrile extraction. Case-control sets were assayed together and samples were ordered randomly and labeled to mask case-control status. Samples were assayed in two batches: cases (and matched controls) diagnosed between 1999 and 2005 and those diagnosed from 2005 to 2007. The overall coefficients of variation (CVs) from masked replicate quality control samples included in each batch were 10.7% and 6.0%. Due to technical difficulties with the assay, three case-control sets failed and were removed, resulting in our final study population of 613 cases and 1,218 controls.We obtained breast cancer risk factor information from a questionnaire completed at the time of blood collection and from the biennial NHSII questionnaires. Age at menarche, weight at age 18, and height were queried in 1989. Age at first birth, parity, and diagnosis of benign breast disease were assessed biennially. Family history of breast cancer in the participant's mother and sisters was queried in 1989 and 1997. Weight was assessed at the time of blood collection.Quartile cut points were defined in two ways, based on the distribution in controls. The first set of cut points was calculated among all controls. Next we calculated season-specific cut points, using November to April blood collection dates to define "winter" and May to October blood collection dates to define "summer". We identified statistical outliers using the generalized extreme studentized deviate many-outlier detection approach . AlthougP-values were based on two-sided tests and were considered statistically significant if ≤0.05. All analyses were conducted using SAS software version 9 .We used conditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) to adjust for the matched design of this study. Multivariate models adjusted for body mass index (BMI) at age 18 and at the time of blood collection, ages at menarche and first birth, parity, family history of breast cancer, and history of benign breast disease. Given that outdoor physical activity may serve as a proxy for sun exposure, an important source of vitamin D, our main model did not include physical activity but we adjusted for it in a sensitivity analysis. In stratified analyses, we used unconditional logistic regression, adjusting for matching factors, since results from multivariate unconditional and conditional logistic regression models were essentially identical. To test whether the association differed by ER and PR status of the tumor, we used polychotomous logistic regression  with thrCases had slightly lower BMI at age 18 and at blood collection and had gained less weight since age 18 than controls  , with adjustment for BMI at blood collection accounting for the majority of the difference between the simple and multivariate estimates. To assess the impact of physical activity, which could be both a confounder and a source of vitamin D, we added it to our multivariate model; results still were not significant , P-value, test for trend = 0.14). Analyses using season-specific cut points were similarly null , P-value, test for trend = 0.79). Using restricted cubic spline models, no significant linear or non-linear associations were detected.In the simple conditional logistic regression model accounting for matching factors only, women in the highest quartile of 25(OH)D were not at significantly different risk of breast cancer compared with women in the lowest quartile , N = 415), results were similar to the overall , P-value, test for trend = 0.14). RRs also were similar across hormone receptor subtypes .Analyses by tumor subtype did not show any significant differences Table . When weN = 470 cases) were still null , P-value, test for trend = 0.29), as were results of analyses restricted to women premenopausal at diagnosis (N = 294 cases) , P-value, test for trend = 0.16). Results also were unchanged when we excluded cases diagnosed in the first two years , P-value, test for trend = 0.91).To assess whether the association between 25(OH)D levels and breast cancer risk differed by other factors, we conducted secondary analyses restricted to premenopausal women and women diagnosed more than two years after blood collection. Results of analyses restricted to women who were premenopausal at blood collection (2), and season of blood collection (winter vs. summer)  and a significant positive association among overweight and obese women , P-value, test for trend = 0.005). The interaction between plasma 25(OH)D and BMI was statistically significant  and a significant linear association was observed in restricted cubic spline models for BMI ≥ 25 (P = 0.007) but no significant association for BMI < 25 (P = 0.09). No non-linearity of 25(OH)D in either BMI strata was evident. Results were unchanged when stratified by age at blood collection .We also stratified by age at blood collection (< 45 vs. ≥ 45), BMI at blood collection (< 25 vs. ≥ 25 kg/mr) Table . When weP-value, test for heterogeneity < 0.001), the numbers are small and the effects in each strata of family history are not clear . Results among women with luteal phase samples were similar to overall results (data not shown).Additional stratified analyses included family history of breast cancer and among blood samples collected from premenopausal women in the luteal phase of the menstrual cycle. Although there was a significant interaction by family history of breast cancer , P-value, test for trend = 0.44; P-value, test for heterogeneity = 0.33) or season-specific cut points , P-value, test for trend = 0.95, winter RR = 1.22, 95% CI (0.81 to 1.82), P-value, test for trend = 0.52) (Table The association between 25(OH)D and breast cancer did not vary by season of blood collection using overall cut points , When we corrected for random within-person and laboratory error using the reproducibility data (intraclass correlation coefficient (ICC) = 0.72), results were largely unchanged  uncorrected and RR = 1.11, 95% CI (0.83 to 1.48) corrected).In this analysis among predominantly premenopausal women, we did not observe an inverse association between plasma 25(OH)D levels and breast cancer risk overall. These results did not change when restricted to invasive cases, cases diagnosed more than two years after blood collection, or women who were premenopausal at diagnosis. Results were not substantially different between strata defined by age at blood collection or season of blood collection. Stratification by BMI yielded a significant interaction, with a significant positive association observed among overweight and obese women.P-value, test for trend = 0.06) [P-value, test for trend = 0.20) [P-value, test for trend = 0.81), 1.09 , respectively) [P-value, test for trend = 0.78) and a non-significant positive association was observed among the 196 premenopausal cases , P-value, test for trend = 0.14) [N = 54) , P-trend = 0.11) [n = 100 cases), plasma 25(OH)D levels measured during pregnancy were not significantly associated with breast cancer risk , P-value, test for trend = 0.4) [To date, only seven prospective studies of circulating 25(OH)D levels and breast cancer risk have been conducted -27. Resu = 0.06) . Results = 0.20) . Howeverctively) ,24. In t = 0.14) . In contThe significant interaction we observed by BMI was unexpected. Although a significant interaction by BMI also was observed in the NHS study of 25(OH)D and colon cancer, in that study, a stronger inverse association was observed among leaner women . Five prThe prior analysis in the NHS suggested that higher 25(OH)D levels may be associated with a lower risk of ER- or ER-/PR- disease, but no difference by hormone receptor status was observed in the CPSII cohort ,24. In tThis study has several strengths, including the large number of premenopausal cases, extensive information on potential confounders, and blood samples collected before diagnosis. Although this analysis includes only one measure of plasma 25(OH)D to represent longer-term exposure, we have showed good reproducibility of this analyte over a two- to three-year period in the NHS (ICC = 0.72) .While higher plasma 25(OH)D levels have been hypothesized to reduce breast cancer risk, our results suggest such a benefit may not be observed among premenopausal women.2D: 1,25-dihydroxyvitamin D3; BMI: body mass index; CI: confidence interval; CPSII: Cancer Prevention Study II; CV: coefficient of variation; ER: estrogen receptor; ICC: intraclass correlation coefficient; NHS: Nurses' Health Study; NHSII: Nurses' Health Study II; PR: progesterone receptor; RR: relative risk25(OH)D: 25-hydroxyvitamin D; 1,25(OH)The authors declare that they have no competing interests.AHE conceived of the study design, acquired and analyzed the data, interpreted the data and wrote the manuscript. DS provided statistical expertise, contributed to the analysis and interpretation of the data, and critically reviewed the manuscript. BWH assisted in the interpretation of the data and critically reviewed the manuscript. RLH performed the 25(OH)D assay and critically reviewed the manuscript. WCW and SEH conceived of the study design, secured funding, acquired the data, contributed to the analysis and interpretation of the data, and critically reviewed the manuscript. All authors read and approved the final manuscript.


Prevalence of breast cancer in Asian developing countries is much lower than western developed countries. The main aim of this study was to measure breast cancer prevalence in a defined population of Iran.A total of 25201 women who were under coverage of “Imam Khomeini Relief Foundation (IKRF)”, which is an organization for delivering supportive social and cultural services to the deprived and poor subgroups of the society, were involved in the study. The study was conducted during years 2007 and 2008. All subjects were interviewed for their socio-demographic features and underwent precise clinical and para-clinical breast examination.Mean age was 47 years with standard deviation 10 ranging from 11 to 88 years. Subjects were from deprived subgroups of the community; were mainly illiterate or had primary school education (86%) and majority of them (93%) had their first full-term pregnancy at age less than 26 years and also were multiparous. With confirmed diagnosis by breast biopsy, breast cancer prevalence was 0.15% .Compared with developed countries, Asian developing countries have been at a lower risk of breast cancer development. It is seen that more deprived subgroups are at much lower risk. The more industrialized life is accompanied with more hazards. Breast cancer is the most frequently diagnosed malignancy among women in developed countries,2]3] an[3] an2][ an[3] anBreast cancer usually occurs at the time when women have important family and occupational roles, and thus any treatment in relation to this cancer would be particularly stressful for the patient and her family. Disparities in the prevalence of breast cancer have long been debated. As mentioned before the prevalence of breast cancer is low in Iran. The main aim of this study was to measure the prevalence of breast cancer in a specific group of women from low social class and deprived subgroups of Iranian population.A total of 25201 women who were insured by the “Imam Khomeini Relief Foundation (IKRF)” were involved in this study. The “Imam Khomeini Relief Foundation (IKRF)” was established in 1980 in Islamic Republic of Iran for delivering supportivesocial and cultural services to deprived and poor subgroups of the society. Thus women in this study were mainly Vulnerable Household Women’s Health Assessment (VH-WHAT) from poor and low social subgroups1. This stuIslamic Republic of Iran, in the Middle East region with an over 70 million population, consists of 30 provinces with Tehran as its capital with more than 10 million residents. Along with Tehran, 10 more province capitals including: Shiraz, Mashhad, Kerman, Kermanshah, Bushehr, Qom, Isfahan, Gorgan, Rasht and Yazd were included in this study.The statistics and number of vulnerable women was obtained from the provincial public service organizations (IKRF). Population size of each province capital was determined according to its population and allocated budget.All of the subjects were first interviewed for socio-demographic data, drug history and history of cancer. Selected gynecologists and surgeons attended educational workshops to be oriented regarding the principals of a concise breast examination. Then in the appointment day, a gynecologist or surgeon performed a complete breast examination to detect any lump or mass along with axillary lymph node exam. All par-ticipants in the range of 35 to 60 years then referred to designated radiology centers for mammography. For those women above 60 or below 35 years of age, mammography was done according to physician’s opinion and results of breast examination.In some cases with suspicious results of mammography, a breast ultrasonography was performed to evaluate any abnormal mass or lumps; in presence of any cystic lesion it was aspirated by needle. All suspicious breast masses underwent biopsy for detection of malignant lesions and the breast cancer diagnosis was confirmed by the result of biopsy. All analysis was conducted using Stata v10.Mean age of the population study was 47 years with standard deviation of 10 years, ranging from 11 to 88 years. Only 2% were single while 19% were married and 79% were divorced or widowed women. Fifty eight percent reported their menarche at age 13 years or less and the rest at 14 years and above. Age of marriage in 70% of them was 18 years or less and in 26% was 19 to 25 years and only 4% had age of marriage at age 26 years or above. Fifty five percent had their first pregnancy at age 18 or less and 37% between age 19 to 25 and only 8% at age 26 years and above. Eighty eight percent were unemployed and received their life expenses from IKRF. Forty percent were illiterate and 47% had only primary school education and only 3% had university education. Forty six percent had never used OCP, 47% had started to use OCP between ages 20 to 30 years and 7% at age above 30 years. However, duration of OCP use was not clear for the two last groups .Number of pregnancies was significantly associated with diagnosis of breast cancer and those with a higher number of pregnancies were less likely to be diagnosed with breast cancer. Marital status, menarche age, age of marriage, age at first pregnancy, occupation and education were not associated with the disease diagnosis.About 1% of subjects had history of radiation exposure and 6% had reported hormone therapy before the time study and these two factors were not associated with the disease diagnosis. Positive family history of both breast cancer and ovarian cancer was about 3%. Also family history of breast and ovarian cancer were significantly related and those with family history of one cancer were more likely to have family history of another. Eighteen percent of breast cancer patients had reported family history of all other cancers. Only one of the breast cancer patients had been previously diagnosed with ovarian cancer. History of cancer in subjects and their families was not associated with the disease diagnosis.All of the subjects were examined for benign changes in breast skin and nipple like redness and exfoliation. However, none of diagnosed patients with breast cancer had these changes in their breasts. Final diagnosis of breast cancer was confirmed in 38 of 25201 subjects of study which was 0.15%, 95%CI; 0.10-0.20.The results of this study showed that prevalence of breast cancer in the specific population of study was 0.15% which is much lower than other studies on breast cancer prevalence from Iran.11] The  The 11] Eighty six percent of our study population were illiterate or had education level less than 6 years. A 36% lower risk was observed for women with more than 16 years of education as compared to those with the lowest educational achievement (7-9 years). Alcohol These characteristics of our study population could be a reason for the very low prevalence of breast cancer among them. Moreover, all subjects were from a low social class and deprived subgroups of Iran's population. Although recent studies have shown that breast cancer risk is increasing in developed countries, some studies reported that changes in risk of breast cancer differs in various thnicities.16] The  The 16] Furthermore, despite the high prevalence, the prognosis of breast cancer is better in the developed countries. However, although the prevalence of breast cancer in Iran is lower than that in the developed countries, the overall prognosis is worse. Since th


Factors across the life cycle, beginning before birth, influence breast cancer risk. We know this from epidemiologic studies of characteristics self-reported by older women or gleaned from medical records. For example, larger babies have higher breast cancer risk decades later, and preeclampsia is associated with lower risk in daughters . EarlierIf environmental chemicals have comparable effects during sensitive developmental periods, identifying these risks could lead to prevention. However, epidemiologic data to assess the effects of chemicals in early life are rarely attainable. Exceptional events or decades-long cohort studies can provide some information. For example, studies of atom bomb survivors revealed breast cancer risk was highest from radiation exposure to young girls . A uniquin utero and during other windows of development set the stage for chronic diseases later in life. New procedures include dosing in utero and throughout development, adding morphological and functional assessments of reproductive organs, and including longer-term follow-up, none of which are included in traditional toxicity testing. For example, new protocols recently demonstrated that in utero antiandrogen exposure in rodents leads to altered male reproductive development, as well as reduced fertility and possibly increased cancer later on. These observations are thought to parallel human “testicular dysgenesis syndrome,” which includes decreased fertility and increased incidence of cryptorchidism, hypospadias, and testicular cancer  , but theAlthough traditional cancer bioassays have identified many common pollutants that increase mammary gland tumors, including common air pollutants, drinking water disinfection by-products, and chlorinated solvents , researc


Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk . The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required. Breast cancer is one of the most common cancers affecting the morbidity and mortality of females worldwide . While nThe p53 tumor suppressor gene contains 11 exons, located on chromosome 17p13. The codon 72 polymorphism (rs1042522) is located in exon 4 with a CGC to CCC transition, leading to an arginine to proline amino acid substitution in amino acid position 72 (Arg72Pro). Studies have reported that the codon 72 polymorphism is associated with a risk for the development of cancer . The twoPubMed was searched using the terms ‘p53’, ‘polymorphism’ and ‘breast cancer’ . The search was limited to English-language papers. Additional studies were identified by a manual search of the references of original studies. Of the studies with the same or overlapping data published by the same investigators, the most recent ones with the largest number of subjects were selected. Case-control studies containing available genotype frequencies of Arg72Pro were selected.χ2 test. The power of the correlation between the p53 codon 72 polymorphism and breast cancer risk was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). The risks of breast cancer for the GC and CC genotypes, relative to the wild-type GG homozygote were assessed; then, the risks of breast cancer for GC/CC vs. GG and CC vs. GC/GG, and finally the supercilious dominant and recessive effects of the variant C allele were determined. Stratified analyses according to background, the source of controls and clinicopathological individuality were also performed. In considering the possibility of heterogeneity across the studies, an arithmetical test for heterogeneity was performed based on the Q-test. P<0.05 for the Q-test was considered to indicate a lack of heterogeneity among the studies. The summary OR estimate of each study was calculated by the random effects model (For the control group of each study, the allelic occurrence was considered and the observed genotype frequencies of the p53 codon 72 polymorphism were assessed for Hardy-Weinberg equilibrium using the ts model ,18. The ts model . All staSixty-one case-control studies concerning the association between p53 codon 72 polymorphism and breast cancer were identified, which included 28,539 breast cancer cases and 32,788 controls. These data were used in a meta-analysis . The shaThe results of the association between the p53 codon 72 polymorphism and breast cancer and the heterogeneity test are shown in Given the important roles of p53 in multiple cellular functions, including gene transcription, DNA repair and apoptosis, it is biologically plausible that p53 polymorphisms may be associated with a risk of breast cancer . Human bAlthough a number of previous studies have reported a significant association between the p53 codon 72 polymorphism and breast cancer risk –34, otheIn conclusion, this meta-analysis, with a large model size, provides a strong indication that the p53 codon 72 polymorphism is not associated with breast cancer risk. Future studies should extend this investigation by incorporating other potential risk factors for breast cancer.


The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer.The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20–45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors’ high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors’: a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives’ baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention.The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.NCT01612338 Breast cancer is the second most common cancer among U.S. women and the second leading cause of cancer death . One of Breast cancer survivors have a 2-fold higher risk of developing a second breast cancer, compared to women without breast cancer, matched for age, breast density, and use of mammography . In addiThe study aims to increase breast cancer surveillance and early detection by targeting YBCS identified from a state cancer registry and their high risk relatives. Specific aims are to:Aim 1: Identify and survey 3,000 female YBCS reported to the cancer registry who were diagnosed between the ages of 20–45 years and determine: (a) their current breast cancer screening status; (b) perceived barriers and facilitators to screening; (c) willingness to participate in an intervention to increase breast cancer screening; and (d) willingness to serve as a breast cancer screening advocate for their high-risk relatives.Aim 2: Identify and survey up to two unaffected first- and/or second-degree female relatives per YBCS and determine: (a) their current breast cancer screening status; (b) perceived barriers and facilitators to screening; and (c) willingness to participate in an intervention to increase breast cancer screening. Female relatives will be between 25–64 years and have an increased risk of breast cancer based on the YBCS’ age of diagnosis.Aim 3: Compare the efficacy of two versions of an intervention on breast cancer screening utilization and other outcomes among YBCS and their high-risk female relatives. YBCS and their high-risk female relatives will be randomly assigned as a family unit to receive either the Targeted or the Enhanced Tailored version of the intervention. (Description of the two intervention methods follows).This prospective, randomized trial involves testing the efficacy of two versions of a printed intervention . Participants will be randomly assigned as family units  to receive one of two versions. The survivor and relative(s) of enrolled family units will be mailed a self-administered baseline survey prior to receiving the intervention (Time 1). A self-administered, follow-up survey will be mailed to YBCS and high-risk relatives nine months post-intervention (Time 2).in situ and invasive malignancies. Between 1998 and 2007, there were 7,866 YBCSs identified in the Michigan Cancer Surveillance Program [The Michigan Cancer Surveillance Program is a central cancer registry that was established by law (Act 82 of 1984) [ Program . This daBetween 1994 and 2008 there were 9,000 cases of young women with breast cancer were reported to the Michigan Cancer Registry. For the study, 3,000 women diagnosed with invasive or in –situ-breast cancer between 20 to 45 years old from 1994 to 2008 will be randomly selected from the cancer registry database. The Michigan Cancer Surveillance Program will cross-reference mortality data to exclude deceased YBCS. To increase inclusion of minority and underserved women, the sample will be stratified by race. The study will oversample YBCS who are black and living in counties with the highest mortality rates for young women with breast cancer  Obtain approval to conduct research with human subjects from the Institutional Review Boards at the University of Michigan and at the Michigan Department of Community Health, and the Scientific Advisory Board of the Michigan Cancer Registry.2) The cancer registry will send a letter to the reporting facility and the physician of record asking if they are aware of any reason that the YBCS should not be contacted to participate in the study. The YBCS will be excluded from the study if the reporting facility or physician of record responds to this letter requesting that the YBCS not be contacted.3) If there is no reason to exclude YBCS, the cancer registry will mail an invitation letter to the YBCS requesting her participation in the study, along with an Informed Consent form, and the self-administered baseline survey. The invitation letter and consent form will explain the study and state that if the YBCS is currently incarcerated or institutionalized, or if she is pregnant, she is not eligible to participate. The invitation letter will explain that these two conditions may interfere with a woman being able to get breast cancer screening. The invitation letter and consent form include contact information for the Director of the cancer registry and the Principal Investigator of the study, and a toll-free phone number for the Michigan Department of Community Health-Genomics Program for the YBCS to ask further questions about the study.4) YBCS who agree to participate will return the signed consent form and the completed baseline survey to the cancer registry in a postage-paid, pre-addressed envelope. There will be up to three mailed attempts to reach non-responding YBCS. The cancer registry will not release any identifiable information to the research team until the YBCS mails back her signed consent form and her baseline survey.BRCA1, BRCA2, Lynch, PTEN Hamartoma Tumor, Li-Fraumeni, or Peutz-Jeghers syndromes, the genetic counselors will contact her by phone and provide additional information to raise awareness about appropriate resources and clinical care. These YBCS (estimated n = 100) will be excluded from Aim 3 of the study.5) Once an YBCS agrees to participate, her contact information and baseline survey will be released to the Michigan Department of Community Health-Genomics Program. Two board-certified genetic counselors employed by the program will review all returned surveys to ascertain YBCS eligibility. If the YBCS reports being diagnosed with a known hereditary cancer syndrome such as 6) Based on information provided by the YBCS in the baseline survey, the genetic counselors will identify up to two high-risk relatives per YBCS. Eligible high-risk relatives will be female, first- and/or second-degree relatives, and unaffected by cancer. Identification of high-risk relatives will be according to a protocol that involves pedigree analysis. Questions that assess family history of cancer allow calculations of Gail  and Clau7) Relatives’ signed consents and completed baseline surveys will be returned to the Michigan Department of Community Health-Genomics Program. This is the first time that the research team will receive identifiable information from high-risk relatives. The genetic counselors will review relatives’ signed consent forms to further ascertain eligibility for participation. After randomization, the genetic counselors will also calculate objective breast cancer risk for the high-risk relatives who will be randomized to receive the Enhanced Tailored version of the intervention. The Gail model  and the 8) YBCS and high-risk relatives will receive a check for $10 in the mail when they return their baseline survey and a check for $20 when they return their follow-up survey.Before randomization, YBCS (with and without high-risk relatives) will be stratified by self-reported race (black vs. other) to ensure equal distribution of ethnic minority participants across study arms. YBCS (n = 960 with high-risk relatives and n = 240 without high-risk relatives) will be randomly allocated to receive either the Targeted or the Enhanced Tailored version of the intervention via a computerized program generated by the study statistician. YBCS and high-risk relatives will be randomly assigned as a family unit.An expansion of the Theory of Planned Behavior (TPB)  was usedth grade reading level or less.Development of the Targeted version is based on a mailed intervention recommended by the Guide to Community Preventive Services as efficacious in increasing breast cancer screening among older, non-adherent women . ParticiTailored health messages have the greatest advantage over targeted messages when there is significant variability within the targeted audience on key determinants of the intended outcome, e.g., knowledge and attitudes . When thA follow-up survey will be mailed to YBCS and their high-risk relatives nine months after the baseline survey to determine the effect of each intervention version on: a) utilization of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing screening services; d) family support related to screening; e) knowledge of the genetics of breast cancer; and f) satisfaction with the intervention. Table Data analyses to meet Aim 3 will require comparison of randomly assigned subsamples of the entire sample and make the most demand on the sample size. PASS software  was usedT-test for differences in means) to assess the associations between demographic factors, clinical indications and screening practices will follow. We will stratify by using the Cochran-Mantel-Haenszel test to assess the association between family history, screening practices, genetic counseling/testing, and perceived facilitators/barriers while controlling separately for race/ethnicity, age-group, and time since diagnosis. Outcomes include both continuous and dichotomous measures. Means and standard deviations will be used to describe the results. Continuous measures taken only at post-test will be compared between the two intervention groups by simple t-tests. After assuming an autocorrelation of data r = .30, changes over time in continuous measures will be tested by paired t-tests. For dichotomous measures taken only at post-test, the rates in the two groups will be compared by logistic regression. The proportions in each group will be reported to describe the results. If a baseline version of the measure is available, logistic regression will be conducted on the post-tests with the pre-tests included as covariates. Chi-square tests will be conducted to test the changes over time. The above analyses will establish whether the groups are equivalent, determine whether post-tests differ between the two groups, and assess the significance of changes over time. To further meet Aim 3, regression analyses (linear or logistic) will be used to test which factors (beyond the intervention) predict obtaining breast cancer screening.Analyses will be conducted separately for YBCS and high-risk relatives. A descriptive analysis of baseline data will provide screening utilization practices, perceived barriers and facilitators to screening, and other outcomes for YBCS and high-risk relatives. This will include tabulating counts and frequencies of variables including demographics, cancer history, screening history and perceived breast cancer risk. Bivariate analyses , the study aims to increase breast cancer screening among women at greatest risk for breast cancer. This innovative approach of identifying high-risk women through existing public health data may lead to a new method of family history collection and breast cancer risk assessment. Third, this study is among the first to evaluate two versions (Targeted vs. Enhanced Tailored) of a printed intervention as a means of increasing breast cancer screening in YBCS and their high-risk female relatives. This novel approach will likely expand our knowledge about interventions that can increase breast cancer screening among women at substantially higher risk.YBCS: Young breast cancer survivor; DCIS: Ductal carcinoma in situ; CA: Cancer.The authors declare that they have no competing interests.MK developed the two versions of the intervention and the study protocol and will oversee the overall scientific integrity of the study. LN developed the two versions of the intervention and the study protocol. AS developed the two versions of the intervention and the study protocol. SD developed the two versions of the intervention and the study protocol. DD assisted in the development of the study protocol and the intervention and will evaluate family history, identify high-risk relatives, calculate objective breast cancer risk, and act as a “Project Navigator.” DR provided the proposed statistical analyses. BA assisted in the development of the study protocol, methods for subject recruitment, and statistical analyses. NJ provided consultation on the development of the two versions of the intervention. JM assisted in subject eligibility criteria and will evaluate family history, identify high-risk relatives, calculate objective breast cancer risk, and act as a “Project Navigator.” KM assisted in subject eligibility criteria and will evaluate family history, identify high-risk relatives, calculate objective breast cancer risk, and act as a “Project Navigator.” SM provided consultation on subject eligibility criteria and the development of the intervention and the study protocol. LMD reviewed the manuscript and provided comments as a scientific collaborator at the Centers of Disease Control and Prevention. She is collaborating with the Principal Investigator on programmatic issues. GC assisted with methods for study recruitment. All authors contributed to the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/97/prepub


Both dietary and serum levels of inorganic phosphate (Pi) have been linked to development of cancer in experimental studies. This is the first population-based study investigating the relation between serum Pi and risk of cancer in humans.From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (> 20 years old) with baseline measurements of serum Pi, calcium, alkaline phosphatase, glucose, and creatinine . Multivariable Cox proportional hazards regression analyses were used to assess serum Pi in relation to overall cancer risk. Similar analyses were performed for specific cancer sites.We found a higher overall cancer risk with increasing Pi levels in men ( HR: 1.02 (95% CI: 1.00-1.04) for every SD increase in Pi), and a negative association in women (HR: 0.97 (95% CI: 0.96-0.99) for every SD increase in Pi). Further analyses for specific cancer sites showed a positive link between Pi quartiles and the risk of cancer of the pancreas, lung, thyroid gland and bone in men, and cancer of the oesophagus, lung, and nonmelanoma skin cancer in women. Conversely, the risks for developing breast and endometrial cancer as well as other endocrine cancer in both men and women were lower in those with higher Pi levels.Abnormal Pi levels are related to development of cancer. Furthermore, the in verse association between Pi levels and risk of breast, endometrial and other endocrine cancers may indicate the role of hormonal factors in the relation between Pi metabolism and cancer. Inorganin vitro,4. Moreoin vitro-7, whichBesides being naturally present in raw food including meats, fish, eggs, dairy products and vegetables, Pi is also found as an additive in processed food such as hamburgers and pizza, and as phosphoric acid in soda beverages. Mostly,The Swedish Apolipoprotein Mortality Risk (AMORIS) database has been described in detail elsewhere-17. Briest of December 2002), whichever occurred first. The CALAB database also contained information on age, season at time of measurement, and fasting status. Diagnosis of cancer were obtained from the National Cancer Register and classified based on the International Classification of Diseases, seventh revision . Socioeconomic status (SES) was taken from the consecutive Swedish censuses during 1970–1990 and is based on occupational groups and classifies gainfully employed subjects into manual workers and non-manual employees, below designated as blue-collar and white-collar workers[We selected all participants aged 20 or older with baseline measurements of serum Pi, calcium (mmol/L), alkaline phosphatase (mmol/L), glucose (mmol/L) and creatinine (μmol/L) . All participants were free from cancer at time of entry and none were diagnosed with cancer or died within three months after study entry. Follow-up time was defined as the time from measurement until date of cancer diagnosis, emigration, death, or study closing date (31 workers. HistorySerum inorganic phosphate was measured via formation of the phosphomolybdic acid complex (coefficient of variation ≤4%). To asseMultivariate Cox proportional hazards models were used to investigate quartiles and standardized values of serum Pi as a continuous variable in relation to overall incident cancer. All models were adjusted for age, gender and SES. We also took into account serum glucose, fasting status and history of diabetes based on hospital discharge diagnosis since diabetes is known to modify the risk of cancer and Pi metabolism is abnormal in diabetic persons,25. The A total of 31,482 persons developed cancer during mean follow-of 12.75 years. Most measurements were taken as part of health examinations done at company health check-ups, so that the majority of the study population (84%) was gainfully employed  treatment compared to those treated with low Pi diet[ll cycle.We found a clear inverse association between Pi levels with risks of female breast and endometrial cancers as well as “other endocrine cancers”, which drove the inverse relation with overall cancer risk in women. Breast and endometrial cancers are well-known to be affected by hormonal factors, especially estrogen,40. IncrThe major strength of this study is the large number of subjects with baseline measurements of serum Pi, all measured in the same laboratory. The use of national registers provided detailed follow-up information on diagnosis of cancer, time of death, and emigration for all subjects. The AMORIS population was mainly selected based on the availability of blood samples from health check-ups in non-hospitalized individuals. However, this healthy cohort effect would not affect the internal validity of the current study and is likely to be minor since it has been shown that the AMORIS cohort is similar to the general working population of Stockholm County in terms of SES and ethnicity. A limitOur findings provide novel epidemiological evidence revealing a decreased cancer risk in women with high Pi and increased risk in men with high Pi. However, women with high Pi displayed a higher risk for developing some specific cancers including oesophageal, lung, and nonmelanoma skin cancer. The persistent negative link between Pi levels and the risk of breast, endometrial and other endocrine cancers which drove the inverse relation between Pi and overall cancer risk in women may imply that Pi rather serves as a proxy for underlying hormonal or metabolic factors instigating carcinogenesis. Further studies in this field should take into account these hormonal and metabolic factors involved in Pi metabolism and also the role of dietary Pi, while also addressing the impacts of other cancer-related effect modifiers beyond the coverage of the current study.None declared. Niklas Hammar is employed by the AstraZeneca Sverige, Södertalje, Sweden and the views of the present study are his own and not necessarily any official views of the AstraZeneca Sverige.WW designed the study, analyzed the data, interpreted analysis results, and wrote the paper. KM interpreted analysis results and edited the manuscript. HG NH IJ GW LH contributed to the analysis tools and database used in this study and edited the manuscript. MVH conceived and designed the study, interpreted analysis results, and edited the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/257/prepub


Mammographic density, a strong predictor for breast cancer incidence, may also worsen prognosis in women with breast cancer. This prospective analysis explored the effect of prediagnostic mammographic density among 607 breast cancer cases diagnosed within the Hawaii component of the Multiethnic Cohort (MEC).Female MEC participants, aged ≥ 50 years at cohort entry, diagnosed with primary invasive breast cancer, and enrolled in a mammographic density case-control study were part of this analysis. At cohort entry, anthropometric and demographic information was collected by questionnaire. Tumor characteristics and vital status were available through linkage with the Hawaii Tumor Registry. Multiple digitized prediagnostic mammograms were assessed for mammographic density using a computer-assisted method. Cox proportional hazards regression was applied to examine the effect of mammographic density on breast cancer survival while adjusting for relevant covariates.Of the 607 cases, 125 were diagnosed as in situ, 380 as localized, and 100 as regional/distant stage. After a mean follow-up time of 12.9 years, 27 deaths from breast cancer and 100 deaths from other causes had occurred; 71 second breast cancer primaries were diagnosed. In an overall model, mammographic density was not associated with breast cancer-specific survival , but the interaction with radiotherapy was highly significant (p = 0.006). In stratified models, percent density was associated with a reduced risk of dying from breast cancer  in women who had received radiation, but with an elevated risk  in patients who had not received radiation. High breast density predicted a borderline increase in risk for a second primary .Assessing mammographic density in women with breast cancer may identify women with a poorer prognosis and provide them with radiotherapy to improve outcomes. Mammographic density - the distribution of fat, connective, and epithelial tissue in the breast - has been used as a biomarker because a high percentage of dense parenchyma on mammographic images confers a four- to six-fold risk for breast cancer , but itsin situ (DCIS) patients with highly dense breasts [So far, six reports have examined the influence of mammographic density on breast cancer outcomes: three on recurrence -14 and t breasts , and two breasts ,14. Thre breasts , but no  breasts  or a US  breasts  cohort. A nested case-control study  within tAs described previously, multiple mammographic films were obtained for each woman to cover a wide time period; cases had a mean of 3.2 density measures . The val+/PR+), (b) ER- or PR-, or unknown. Because it was not routinely performed before 2000, HER2/neu was not available.We used the SAS package, release 9.3  for all analyses. Follow-up time was calculated from the date of diagnosis until the earliest event of interest . We used three approaches to examine percent density: as a continuous variable rescaled and expressed per 10% increase, as a dichotomous variable classified into low and high by using the median of 35%, and as three categories . Body mass index (BMI) was categorized as normal, overweight, or obese. Because of the small number of events, hormone receptor status was classified as a two-level variable: (a) estrogen receptor-positive/progesterone receptor-positive , P = 0.38) and the HR for the overall model changed less than 10% (0.95 to 0.92), we decided not to include them. Given the previously reported effect modification by radiotherapy [Cox proportional hazard regression was applied to explore the relation of breast density with deaths due to breast cancer and other causes separately as well as with the incidence of a second breast cancer. Although mammographic density is unlikely to affect all-cause mortality, the analysis was added to show that breast density is not a marker for high mortality. When modeling second breast cancers, the time between first and second diagnosis was used as the follow-up time. Because a previous analysis in the MEC had shown that tumor stage, weight status, and ethnicity influenced survival, these variables were considered essential covariates ; all throtherapy , we modein situ, 380 as local, and 100 as advanced . After a mean follow-up time of 12.9 years, 27 deaths from breast cancer and 100 deaths from other causes occurred. By category, 215 women had less than 25%, 209 women had 25% to less than 50%, and 183 women had at least 50% breast density (Table Japanese-Americans and Caucasians constituted the largest proportion of study participants Table . Native P = 0.28), and the stage distribution also did not differ (P = 0.43). In total, 361 women received radiation  breast cancer deaths occurred in the low-density and 5 (2.9%) in the high-density group. Among the 246 women without radiation, 1 (0.9%) death was observed in the low-density group and 10 (7.8%) deaths in the high-density group.The age at diagnosis of women with radiation was similar to that of women without radiation . At the same time, the risk estimates became elevated and borderline significant. The stratified models indicated divergent results for the two groups. Percent density was associated with a reduced risk of dying from breast cancer in women who had received radiation  but with an elevated risk in patients who had not received radiation . The results were similar when women were dichotomized by low and high density  and 1.29 (95% CI 0.91 to 1.81); the value for cases who had received radiation did not change and, for those without radiation, was 1.37 (95% CI 0.93 to 2.02).In the overall model with 607 cases, mammographic density did not predict death due to breast cancer Table . The HRsP = 0.15) and more than doubled when women with less than 25% were compared with those with at least 50% density . After exclusion of the 15 primaries that occurred in the ipsilateral breast, the risk estimates were attenuated. For example, the HRs for the intermediate- and high-density categories as compared with less than 25% were 1.15 (95% CI 0.45 to 2.97) and 1.43 (95% CI 0.51 to 4.01), respectively. No interaction with radiation was observed.Mammographic density was not associated with death from other causes when the continuous density variable  or density categories were used. However, the risk for a second breast cancer was 70% higher in women with high density  when the high group of patients was compared with the low-density group, but no association was seen in patients who received radiation, a finding that disagrees with the protective effect of radiation treatment on breast density seen in our study. In an investigation of 136 patients who had all received radiation, local recurrence rates were higher when the top quartile of breast density was compared with the lowest [The interaction seen here between breast density and radiation agrees with a report showing that women with high breast density had a significantly elevated risk to develop local breast cancer recurrence if they had not received radiotherapy . Among 3e lowest . Women we lowest .P = 0.10) [Despite the large number of cases, two mammography cohorts did not detect significant effects of mammographic density on breast cancer survival ,17, wher = 0.10) . The den = 0.10) , and wit = 0.10) .However, the previous studies disagree on whether radiotherapy modifies the association of mammographic density with recurrence -14. WherThe mechanisms underlying the paradoxical lower risk of mortality associated with the joint effects of high breast density and radiotherapy are unclear. Clinical trials have shown that chemotherapy and hormonal treatment have a higher impact on breast cancer survival but that treatment with breast-conserving surgery plus radiation has survival rates similar to those of mastectomy but higher local recurrence rates . TherefoThe major limitations of this study are the small number of deaths and the lack of recurrence information. The outcomes are based on data from a SEER registry, which does not routinely collect recurrence. However, the treatment data obtained directly from the HTR are considered of good quality because of the limited number of such facilities in the State of Hawaii and the low likelihood of receiving treatment out of state. Only 9 out of the 607 (1.5%) cases had a code indicating uncertainty about radiation treatment received. Strengths of our analysis are the availability of repeated mammograms, the long follow-up time, and the high quality of the mammographic density assessment method that provided quantitative estimates rather than qualitative categories.This longitudinal investigation with 13 years of follow-up found an adverse effect of high mammographic density on breast cancer survival among patients who had not received radiation treatment and a lower risk of death from breast cancer in women who had received radiation. To confirm the findings of this exploratory analysis, it appears feasible to reanalyze large breast cancer clinical trials for differences in outcomes according to breast density. Although chemotherapy was not significant in our study, effect modification with other treatment modalities could also be investigated, but there are biologic reasons to think that radiotherapy has a more pronounced effect on stroma, and, in particular, the ECMs that constitute mammographic density, than on breasts with a high proportion of fat tissue. Assessing mammographic density in women with breast cancer may help to identify women with a poorer prognosis. The implications of this research may be important for future treatment of breast cancer in women with high breast density who may benefit from additional radiotherapy.in situ; ECM: extracellular matrix; ER: estrogen receptor; HR: hazard ratio; HTR: Hawaii Tumor Registry; MEC: Multiethnic Cohort; MMP-3: metalloproteinase-3; PR: progesterone receptor; SEER: Surveillance, Epidemiology, and End Results.BMI: body mass index; CI: confidence interval; DCIS: ductal carcinoma The authors declare that they have no competing interests.All authors made substantial contributions to conception and design, analysis and interpretation of data, and critical review of the manuscript. GM conceived of the study, coordinated the data acquisition and analysis, and helped to draft the manuscript. ISP participated in planning the statistical methods and performed part of the analysis. ML helped to draft the manuscript. SMC contributed to the data analysis and drafted parts of the manuscript. LNK and SYP participated in the design of the study and in the statistical analysis. All authors read and approved the final manuscript.