An anti-inflammatory dietary intervention to reduce breast cancer recurrence risk: Study design and baseline data.

U.S. breast cancer survivors (BCSs) are expected to increase to 4 million in the next 5-10years. Cancer recurrence risk is highest among obese survivors. Inflammatory (Pro-I) biomarkers including C-reactive protein (CRP), Interleukins -3, -6, and -8 (IL-3, IL-6, IL-8), and Tumor Necrosis Factor (TNF)-α have been associated with cancer recurrence risk. Nutritional interventions aimed at reducing inflammation (INF) may contribute to reduced cancer recurrence risk, but studies have been limited to animal models. The goals of this one-year, culinary-based, pilot intervention were to: 1) decrease Pro-I biomarkers and increase anti-inflammatory (AI) cytokine, IL-10, by promoting AI food incorporation into BCS diets; and 2) examine intervention effects on cancer risk factors including body mass index (BMI) and circulating adipose stromal cells (ASCs). A total of 153 BCSs were recruited. Overweight and obese women aged 18 or older were randomized into Intervention (IG; n=76) and Control (CG; n=77) groups. CG received monthly nutritional brochures from the American Institute for Cancer Research. IG attended 6 monthly workshops (lectures on AI topics and chef-prepared food demonstrations), and received monthly newsletters and telephone calls incorporating Motivational Interviewing. At baseline, 6- and 12-month assessments, fasting serum was assayed for Pro-I/AI marker and ASC levels. Using R and Stata version 14 (Stata Corp, 2015), no significant differences were found between groups on baseline demographic variables. Correlations between serum cytokine levels, BMI, % body fat, ASCs, and self-reported variables are discussed.

Satisfaction with cancer care among underserved racial-ethnic minorities and lower-income patients receiving patient navigation.

BACKGROUND: Patient navigation is a barrier-focused program of care coordination designed to achieve timely and high-quality cancer-related care for medically underserved racial-ethnic minorities and the poor. However, to the authors' knowledge, few studies to date have examined the relationship between satisfaction with navigators and cancer-related care. METHODS: The authors included data from 1345 patients with abnormal cancer screening tests or a definitive cancer diagnosis who participated in the Patient Navigation Research Program to test the efficacy of patient navigation. Participants completed demographic questionnaires and measures of patient satisfaction with cancer-related care (PSCC) and patient satisfaction with interpersonal relationship with navigator (PSN-I). The authors obtained descriptive statistics to characterize the sample and conducted regression analyses to assess the degree of association between PSN-I and PSCC, controlling for demographic and clinical factors. Analyses of variance were conducted to examine group differences controlling for statistically significant covariates. RESULTS: Statistically significant relationships were found between the PSCC and PSN-I for patients with abnormal cancer screening tests (1040 patients; correlation coefficient (r), 0.4 [P<.001]) and those with a definitive cancer diagnosis (305 patients; correlation coefficient, 0.4 [P<.001]). The regression analysis indicated that having an abnormal colorectal cancer screening test in the abnormal screening test group and increased age and minority race-ethnicity status in the cancer diagnosis group were associated with a higher satisfaction with cancer care (P<.01). CONCLUSIONS: Satisfaction with navigators appears to be significantly associated with satisfaction with cancer-related care. Information regarding the patient-navigator relationship should be integrated into patient navigation programs to maximize the likelihood of reducing caner disparities and mortality for medically underserved racial-ethnic minorities and the poor.

To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region.

BACKGROUND: Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. METHODS AND POPULATION: Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. RESULTS: Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers' unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers' willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors. CONCLUSIONS: Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities.

Attitudes Toward Breast Cancer Genetic Testing in Five Special Population Groups.

PURPOSE: This study examined interest in and attitudes toward genetic testing in 5 different population groups. METHODS: The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences. RESULTS: Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to "follow doctor recommendations" (p=0.017), "concern for effects on family" (p=0.044), "distrust of modern medicine" (p=0.036), "cost" (p=0.025), and "concerns about communication of results to others" (p=0.032). There was a significant inverse relationship between interest and genetic testing cost (p<0.050), with the exception of Latinas, who showed the highest level of interest regardless of increasing cost. CONCLUSION: Cost may be an important barrier to obtaining genetic testing services, and participants would benefit by genetic counseling that incorporates the unique cultural values and beliefs of each group to create an individualized, culturally competent program. Further research about attitudes toward genetic testing is needed among Asian Americans, Native Americans, and Appalachians for whom data are severely lacking. Future study of the different Latina perceptions toward genetic testing are encouraged.

Incidence of hepatocellular carcinoma in Texas Latinos, 1995-2010: an update.

BACKGROUND: A previous study showed Hepatocellular Carcinoma (HCC) rates to be higher among Latinos in Texas and highest among South Texas Latinos compared to other non-Hispanic whites (NHW) and other Latinos in the United States (U.S.). We used more recent data to assess trends in HCC among Texas Latinos and to reassess the elevated HCC incidence rate in Texas Latinos. METHODS: We used data from the U.S. SEER Program and the Texas Cancer Registry to calculate annual and 3-year moving average age-specific and age-adjusted HCC incidence rates, annual percent changes (APCs), and their corresponding 95% confidence intervals for Latinos and NHW in the U.S., Texas and South Texas. RESULTS: Texas Latino male and female incidence rates were 3.1 and 4.0 times higher than their NHW counterparts in SEER regions. Latino males and females in South Texas had the highest rates of HCC incidence overall; rate ratios were 3.6 and 4.2 among South Texas Latino males and females compared to SEER NHW counterparts. There are statistically significant increases in HCC incidence rates in all groups (Texas and South Texas Latinos and NHW groups) and across all age groups. The elevated HCC rates in Texas Latinos are consistent over the 1995-2010 period. CONCLUSIONS: The incidence of HCC among Latinos in South Texas remains higher than elsewhere in the U.S. and warrants closer investigation of potential risk factors related to prevailing conditions unique to the population including higher obesity and diabetes rates, environmental, cultural and socioeconomic factors and possibly genetic predisposition.

Reducing time-to-treatment in underserved Latinas with breast cancer: the Six Cities Study.

BACKGROUND: The interaction of clinical and patient-level challenges following a breast cancer diagnosis can be a significant source of health care disparities. Failure to address specific cultural features that create or exacerbate barriers can lead to less-than optimal navigation results, specifically in Hispanic/Latino women. METHODS: To address these disparities, the study leaders in San Antonio, Texas, and 5 other regional partners of the federally-funded Redes En Acción: The National Latino Cancer Research Network developed a culturally-tailored patient navigation intervention model for Latinas with breast cancer. RESULTS: Compared with control patients, a higher percentage of navigated subjects initiated treatment within 30 days (69.0% versus 46.3%, P = .029) and 60 days (97.6% versus 73.1%, P = .001) following their cancer diagnosis. Time from cancer diagnosis to first treatment was lower in the navigated group (mean, 22.22 days; median, 23.00 days) than controls (mean, 48.30 days; median, 33.00 days). These results were independent of cancer stage at diagnosis and numerous characteristics of cancer clinics and individual participants. CONCLUSIONS: Successful application of patient navigation increased the percentage of Latinas initiating breast cancer treatment within 30 and 60 days of diagnosis. This was achieved through navigator provision of services such as accompaniment to appointments, transportation arrangements, patient telephone support, patient-family telephone support, Spanish-English language translation, and assistance with insurance paperwork.

Depressive symptoms in Latina breast cancer survivors: a barrier to cancer screening.

OBJECTIVE: Depressed mood limits vigilance, risk avoidance or risk reduction. This may reflect inability to follow health care provider recommendations for screening for other cancers. We determined prevalence of depressive symptoms and its role in screening for other cancers in Latina breast cancer survivors. METHOD: A convenience sample of 117 Latina breast cancer survivors completed a questionnaire including the Center for Epidemiologic Studies Depression scale (CES-D) and substantive barriers to following health care provider recommendations. A threshold score of 16 or greater on the CESD was considered elevated symptoms in the past week. Chi-square and T tests were used to evaluate bivariate associations and multiple logistic regression to identify barriers to compliance with recommendations regarding ovarian and colorectal screening. RESULTS: The results showed 31.6% had CESD scores above the threshold, about three times the general population. Cancer screening rates were very low with only five women (4.2%) screened for both ovarian and colorectal cancer. Elevated symptoms were present in 38% of those without colorectal cancer screening and 42% of those without ovarian cancer screening. It is inversely related to screening for colorectal (aOR = 0.44, p = .04), ovarian (aOR = 0.44, p = .09), or either screening (aOR = 0.38, p = .035). CONCLUSIONS: Depressive symptom rates are higher among breast cancer survivors than the general population; rates of screening for other cancers are low. This indicates general failure to comply with recommendations for screening for other cancers among breast cancer survivors. Depressive symptoms may be a barrier to screening. Affective components of survivorship must be addressed in order to make interventions more effective.

Time to definitive diagnosis of breast cancer in Latina and non-Hispanic white women: the six cities study.

Time delay after an abnormal screening mammogram may have a critical impact on tumor size, stage at diagnosis, treatment, prognosis, and survival of subsequent breast cancer. This study was undertaken to evaluate disparities between Latina and non-Hispanic white (NHW) women in time to definitive diagnosis of breast cancer after an abnormal screening mammogram, as well as factors contributing to such disparities. As part of the activities of the National Cancer Institute (NCI)-funded Redes En Acción research network, clinical records of 186 Latinas and 74 NHWs who received abnormal screening mammogram results were reviewed to determine the time to obtain a definitive diagnosis. Data was obtained from participating clinics in six U.S. cities and included demographics, clinical history, and mammogram characteristics. Kaplan-Meier estimates and Cox proportional hazards models were used to test differences in median time to definitive diagnosis by ethnicity after adjusting for clinic site, demographics, and clinical characteristics. Time-to-event analysis showed that Latinas took 2.2 times longer to reach 50% definitively diagnosed with breast cancer relative to NHWs, and three times longer to reach 80% diagnosed (p=0.001). Latinas' median time to definitive diagnosis was 60 days compared to 27 for NHWs, a 59% gap in diagnosis rates (adjusted Hazard Ratio [aHR] = 1.59, 95% CI = 1.09, 2.31; p=0.015). BI-RADS-4/5 women's diagnosis rate was more than twice that of BI-RADS-3 (aHR = 2.11, 95% CI = 1.18, 3.78; p=0.011). Disparities in time between receipt of abnormal screening result and definitive diagnosis adversely affect Latinas compared to NHWs, and remain significant after adjusting for demographic and clinical variables. With cancer now the leading cause of mortality among Latinos, a greater need exists for ethnically and culturally appropriate interventions like patient navigation to facilitate Latinas' successful entry into, and progression through, the cancer care system.

Navigating Latinas with breast screen abnormalities to diagnosis: the Six Cities Study.

BACKGROUND.: Breast cancer is the leading cause of cancer-related deaths in Latinas, chiefly because of later diagnosis. The time from screening to diagnosis is critical to optimizing cancer care, yet the efficacy of navigation in reducing it is insufficiently documented. Here, the authors evaluate a culturally sensitive patient navigation program to reduce the time to diagnosis and increase the proportions of women diagnosed within 30 days and 60 days. METHODS.: The authors analyzed 425 Latinas who had Breast Imaging Reporting and Data System (BI-RADS) radiologic abnormalities categorized as BI-RADS-3, BI-RADS-4, or BI-RADS-5 from July 2008 to January 2011. There were 217 women in the navigated group and 208 women in the control group. Women were navigated by locally trained navigators or were not navigated (data for this group were abstracted from charts). The Kaplan-Meier method, Cox proportional hazards regression, and logistic regression were used to determine differences between groups. RESULTS.: The time to diagnosis was shorter in the navigated group (mean, 32.5 days vs 44.6 days in the control group; hazard ratio, 1.32; P = .007). Stratified analysis revealed that navigation significantly shortened the time to diagnosis among women who had BI-RADS-3 radiologic abnormalities (mean, 21.3 days vs 63.0 days; hazard ratio, 2.42; P < .001) but not among those who had BI-RADS-4 or BI-RADS-5 radiologic abnormalities (mean, 37.6 days vs 36.9 days; hazard ratio, 0.98; P = .989). Timely diagnosis occurred more frequently among navigated Latinas (within 30 days: 67.3% vs 57.7%; P = .045; within 60 days: 86.2% vs 78.4%; P = .023). This was driven by the BI-RADS-3 strata (within 30 days: 83.6% vs 50%; P < .001; within 60 days: 94.5% vs 67.2%; P < .001). A lack of missed appointments was associated with timely diagnosis. CONCLUSIONS.: Patient-centered navigation to assist Latina women with abnormal screening mammograms appeared to reduced the time to diagnosis and increase rates of timely diagnosis overall. However, in stratified analyses, only navigated Latinas with an initial BI-RADS-3 screen benefited, probably because of a reduction in missed diagnostic appointments.

Beneficial effects of a combined navigator/promotora approach for Hispanic women diagnosed with breast abnormalities.

BACKGROUND: Patient navigation (PN) is an emerging strategy to overcome barriers to cancer care. We evaluated the efficacy of PN in improving time of key events in cancer care, including positive screening tests, definitive diagnosis, initiation of therapy, and completion of initial therapy. METHODS: We evaluated PN in a prospective observational study of predominantly poor Hispanic women with an abnormal breast cancer screening or untreated biopsy proven breast cancer (control = 200, intervention = 260). Controls were contemporary record-based patients with positive screening. Analyses were conducted for the entire cohort and separately by ethnic strata. We used χ(2) tests to compare differences in proportions and Kaplan-Meier followed by Cox regression to compare time-to-event curves of the intervention and control groups. RESULTS: The average days from definitive diagnosis to initiation of therapy was significantly reduced overall with PN (PN vs. control, 57 vs. 74 days, P = 0.04). This effect was more pronounced in the Hispanic strata (56 vs. 81 days, P = 0.02). More navigated Hispanic women were diagnosed within 60 days of abnormal screening (62.6% vs. 47.5%, P < 0.01) and more began treatment within 60 days of diagnosis (80% vs. 56.3%, P < 0.01). Navigated Hispanic and other ethnic minority women had a shorter time from positive screening test to definitive diagnosis (16 and 32 days, respectively). CONCLUSIONS: Minority women may have benefited from navigation with shorter times from definitive diagnosis to initiation of therapy. IMPACT: PN intervention may show promise in decreasing some delays that contribute to health disparities among minority women with breast cancer.

Incidence and risk factors for hepatocellular carcinoma in Texas Latinos: implications for prevention research.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in the U.S. despite a decline in cancer overall. Latinos have higher rates of HCC than the general population according to the Surveillance, Epidemiology, and End Results (SEER) Program. Not included in SEER, Texas Latinos make up one-fifth of the U.S. Latino population. To determine whether HCC incidence differs among U.S. and Texas Latinos, this descriptive study compares HCC incidence from 1995 through 2006 among three Latino populations: U.S. SEER, Texas overall and a South Texas subset. To identify lines of prevention research, we compare prevalence of known HCC risk factors among these Latino groups. METHODS: Data were collected from the U.S. SEER Program, Texas Cancer Registry and Texas Department of State Health Services (TDSHS). Annual age-specific and age-adjusted HCC incidence rates, annual percent changes (APCs) and 95% confidence intervals were calculated as well as prevalence of obesity, diabetes, heavy alcohol use and cigarette smoking. RESULTS: Of the three Latino groups compared, South Texas Latinos had the highest age-adjusted HCC incidence rates and SEER Latinos had the lowest (10.6/100,000 (10.1-11.1) and 7.5/100,000 (7.2-7.7), respectively). HCC incidence significantly increased over time (APCs>0) among Latinos in all three geographic groups. Between 1995 and 2006, there was an increase in obesity among all three populations, and obesity was highest among South Texas Latinos. Diabetes increased among U.S. Latinos, and Latino women in South Texas had significantly higher diabetes prevalence than U.S. Latino women. Cigarette smoking and heavy alcohol use were similar among groups. CONCLUSIONS: The incidence of HCC among Latinos in South Texas is higher than elsewhere in the United States. Higher rates of HCC among Texas and South Texas Latinos may be associated with greater prevalence of obesity and diabetes, risk factors for HCC that are amenable to intervention.

Cancer patient navigator tasks across the cancer care continuum.

Cancer patient navigation (PN) programs have been shown to increase access to and utilization of cancer care for poor and underserved individuals. Despite mounting evidence of its value, cancer patient navigation is not universally understood or provided. We describe five PN programs and the range of tasks their navigators provide across the cancer care continuum (education and outreach, screening, diagnosis and staging, treatment, survivorship, and end-of-life). Tasks are organized by their potential to make cancer services understandable, available, accessible, affordable, appropriate, and accountable. Although navigators perform similar tasks across the five programs, their specific approaches reflect differences in community culture, context, program setting, and funding. Task lists can inform the development of programs, job descriptions, training, and evaluation. They also may be useful in the move to certify navigators and establish mechanisms for reimbursement for navigation services.

Serum beta human chorionic gonadotropin levels can inform outcome counseling after in vitro fertilization.

The predictive value of serum beta hCG level for fetal cardiac motion and pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET is a useful predictor of subsequent presence of fetal cardiac activity and live birth and may assist clinicians in counseling patients regarding their IVF outcome.

Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility.

OBJECTIVE: To identify Chlamydia trachomatis antigens that can be used to differentially diagnose tubal factor infertility in comparison with previously reported heat shock protein 60. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Infertile women with and without tubal pathology diagnosed laparoscopically. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antibody responses to C. trachomatis in infertile women with or without tubal pathologies using a C. trachomatis genome-wide proteome array. RESULT(S): Comparison of the antibody profiles revealed 30 C. trachomatis antigens that were preferentially recognized in women with tubal factor infertility, with a detection sensitivity and specificity of 80.6% and 56.5%, respectively, 10 of which showed 100% specificity. A combination of CT443 and CT381 antigens yielded the highest detection sensitivity (67.7%) while maintaining 100% specificity. CONCLUSION(S): These findings have demonstrated that antibodies to CT443 and CT381, when used in combination, have higher sensitivity and specificity in predicting tubal factor infertility than other indicators for tubal factor infertility, such as heat shock protein 60 antibodies (35.5%, 100%) or hysterosalpingogram (65%, 83%). Using a panel of C. trachomatis antigens to serologically diagnose tubal factor infertility can save the patients from undertaking expensive and invasive procedures for determining tubal pathology and choosing treatment plans.

Structural and reliability analysis of a patient satisfaction with cancer-related care measure: a multisite patient navigation research program study.

BACKGROUND: Patient satisfaction is an important outcome measure of quality of cancer care and 1 of the 4 core study outcomes of the National Cancer Institute (NCI)-sponsored Patient Navigation Research Program to reduce race/ethnicity-based disparities in cancer care. There is no existing patient satisfaction measure that spans the spectrum of cancer-related care. The objective of this study was to develop a Patient Satisfaction With Cancer Care measure that is relevant to patients receiving diagnostic/therapeutic cancer-related care. METHODS: The authors developed a conceptual framework, an operational definition of Patient Satisfaction With Cancer Care, and an item pool based on literature review, expert feedback, group discussion, and consensus. The 35-item Patient Satisfaction With Cancer Care measure was administered to 891 participants from the multisite NCI-sponsored Patient Navigation Research Program. Principal components analysis (PCA) was conducted for latent structure analysis. Internal consistency was assessed using Cronbach coefficient alpha (α). Divergent analysis was performed using correlation analyses between the Patient Satisfaction With Cancer Care, the Communication and Attitudinal Self-Efficacy-Cancer, and demographic variables. RESULTS: The PCA revealed a 1-dimensional measure with items forming a coherent set explaining 62% of the variance in patient satisfaction. Reliability assessment revealed high internal consistency (α ranging from 0.95 to 0.96). The Patient Satisfaction With Cancer Care demonstrated good face validity, convergent validity, and divergent validity, as indicated by moderate correlations with subscales of the Communication and Attitudinal Self-Efficacy-Cancer (all P < .01) and nonsignificant correlations with age, primary language, marital status, and scores on the Rapid Estimate of Adult Literacy in Medicine Long Form (all P > .05). CONCLUSIONS: The Patient Satisfaction With Cancer Care is a valid tool for assessing satisfaction with cancer-related care for this sample.

Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants.

OBJECTIVE: We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants' potential role in this process. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Fertility patients with and without endometriosis. INTERVENTION(S): Menstrual endometrium was collected from women with and without endometriosis confirmed surgically. The adherence of ESC/EECs to PMCs was measured. The ESC/EEC CD44 splice variants were assessed using dot-blot analysis. RESULT(S): The ESCs and EECs from women with endometriosis demonstrated increased adherence to PMCs. The predominant CD44 splice variants expressed by ESCs and EECs from women with and without endometriosis were v3, v6, v7, v8, v9, and v10. The ESCs and EECs from women with endometriosis were more likely to express v6, v7, v8, and v9. CONCLUSION(S): Increased eutopic endometrial-PMC adherence and CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions. Elucidation of factors controlling this expression may lead to novel endometriosis therapies.

Modulation of in situ estrogen synthesis by proline-, glutamic acid-, and leucine-rich protein-1: potential estrogen receptor autocrine signaling loop in breast cancer cells.

In situ estrogen synthesis is implicated in tumor cell proliferation through autocrine or paracrine mechanisms especially in postmenopausal women. Several recent studies demonstrated activity of aromatase, an enzyme that plays a critical role in estrogen synthesis in breast tumors. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is an estrogen receptor (ER) coregulator, and its expression is deregulated in breast tumors. In this study, we examined whether PELP1 promotes tumor growth by promoting local estrogen synthesis using breast cancer cells (MCF7) that stably overexpress PELP1. Immunohistochemistry revealed increased aromatase expression in MCF7-PELP1-induced xenograft tumors. Real-time PCR analysis showed enhanced activation of the aromatase promoter in MCF7-PELP1 clones compared with MCF7 cells. Using a tritiated-water release assay, we demonstrated that MCF7-PELP1 clones exhibit increased aromatase activity compared with control MCF-7 cells. PELP1 deregulation uniquely up-regulated aromatase expression via activation of aromatase promoter I.3/II, and growth factor signaling enhanced PELP1 activation of aromatase. PELP1-mediated induction of aromatase requires functional Src and phosphatidylinositol-3-kinase pathways. Mechanistic studies revealed that PELP1 interactions with ER-related receptor-alpha and proline-rich nuclear receptor coregulatory protein 2 lead to activation of aromatase. Immunohistochemistry analysis of breast tumor array showed increased expression of aromatase in ductal carcinoma in situ and node-positive tumors compared with no or weak expression in normal breast tissue. Fifty-four percent (n = 79) of PELP1-overexpressing tumors also overexpressed aromatase compared with 36% (n = 47) in PELP1 low-expressing tumors. Our results suggest that PELP1 regulation of aromatase represents a novel mechanism for in situ estrogen synthesis leading to tumor proliferation by autocrine loop and open a new avenue for ablating local aromatase activity in breast tumors.

Oncogenic potential of the nuclear receptor coregulator proline-, glutamic acid-, leucine-rich protein 1/modulator of the nongenomic actions of the estrogen receptor.

Proline-, glutamic acid-, leucine-rich protein 1 (PELP1), a novel nuclear receptor coactivator, and its expression is deregulated in hormone-dependent cancers, including those of the breast, endometrium, and ovary. PELP1 interacts with estrogen receptor and modulates its genomic and nongenomic functions. In this study, we examined whether PELP1 functions as an oncogene. The overexpression of PELP1 in fibroblasts and epithelial model cells resulted in cellular transformation. PELP1 also enhanced the transformation potential of c-Src kinase in focus formation assays, and PELP1 overexpression potentiated estradiol-mediated cell migratory potential and anchorage-independent growth. Using PELP1-small interfering RNA, we provided evidence that endogenous PELP1 plays an essential role in E2-mediated anchorage-independent growth, cell migration, and cytoskeletal changes. When compared with control vector transfectants, breast cancer cells stably overexpressing PELP1 showed a rapid tumor growth in xenograft studies. Immunohistochemical analysis of PELP1 expression using a tumor progression array of 252 breast carcinomas and normal breast tissue specimens revealed that PELP1 expression is deregulated to a greater degree in higher grade node-positive invasive tumors than in normal breast tissue or ductal carcinoma in situ. Our data suggest that PELP1 is a potential oncogene, that its expression is deregulated during cancer progression, and that PELP1 may play a role in oncogenesis.

Effect of chromium supplementation on insulin resistance and ovarian and menstrual cyclicity in women with polycystic ovary syndrome.

In women with polycystic ovary syndrome, chromium picolinate (200 microg/d) improves glucose tolerance compared with placebo but does not improve ovulatory frequency or hormonal parameters. This pilot study indicates that future studies in the polycystic ovary syndrome population should examine higher dosages or longer durations of treatment.