Building trust and diversity in patient-centered oncology clinical trials: An integrated model.

BACKGROUND/AIMS: Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives. METHODS: A key word-directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust. RESULTS: Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants' and clinical trial team members' interpersonal trust relationship. The "terms" of interpersonal trust are negotiated through the psychological contract. Contract renegotiation occurs in response to cyclical changes within the trust relationship throughout trial participation. CONCLUSION: The Integrated Model of Trust offers a novel framework to interrogate the process by which diverse populations and clinical trial teams build trust. To our knowledge, this is the first model of trust-building in clinical trials that frames trust development through integrated clinical and business perspectives. By focusing on the process, rather than outcomes of trust-building diverse trial participants, clinical trials teams, participants, and cancer centers may be able to better understand, measure, and manage their trust relationships in real time. Ultimately, this may foster increased recruitment and retention of diverse populations to clinical trials.

User Perceptions and Reactions to an Online Cancer Risk Assessment Tool: a Process Evaluation of Cancer Risk Check.

Online cancer risk assessment tools, which provide personalized cancer information and recommendations based on personal data input by users, are a promising cancer education approach; however, few tools have been evaluated. A randomized controlled study was conducted to compare user impressions of one tool, Cancer Risk Check (CRC), to non-personalized educational information delivered online as series of self-advancing slides (the control). CRC users (N = 1452) rated the tool to be as interesting as the control (p > .05), but users were more likely to report that the information was difficult to understand and not applicable to them (p < .05). Information seeking and sharing also were lower among CRC users; thus, although impressions of CRC were favorable, it was not shown to be superior to existing approaches. We hypothesized CRC was less effective because it contained few visual and graphical elements; therefore, CRC was compared to a text-based control (online PDF file) post hoc. CRC users rated the information to be more interesting, less difficult to understand, and better able to hold their attention (p < .05). Post hoc results suggest the visual presentation of risk is critical to tool success.

State-of-the-science of patient navigation as a strategy for enhancing minority clinical trial accrual.

BACKGROUND: Patient navigation programs are emerging that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process as well as outcome measures to evaluate program effectiveness. METHODS: A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. RESULTS: The eligible studies reported on the development of programs for patient navigation in cancer clinical trials, including training and implementation among African Americans, American Indians, and Native Hawaiians. A low rate of clinical trial refusal (range, 4%-6%) was reported among patients enrolled in patient navigation programs. However, few studies reported on the efficacy of patient navigation in increasing clinical treatment trial enrollment. CONCLUSIONS: Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients.

Five National Cancer Institute-designated cancer centers' data collection on racial/ethnic minority participation in therapeutic trials: a current view and opportunities for improvement.

BACKGROUND: To ensure that National Institutes of Health-funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI. METHODS: EMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets. RESULTS: Cancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers. CONCLUSIONS: Catchment area definitions and the collection of patient-level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States.

A Community-Based Prostate Cancer Screening and Education Program for Asian American Men in Medically Underserved Communities.

This study analyzed data from a community-based prostate cancer (PCa) education and screening program (Prostate Outreach Project; POP) to enhance PCa-related knowledge among medically underserved Asian American men. It also examined PCa screening history, clinical abnormalities based on prostate-specific antigen (PSA) tests and digital rectal examination (DRE) results, and follow-up and PCa diagnosis rates. Participants-521 Asian men (251 Vietnamese, 142 Chinese, and 128 South Asians)-were offered PCa screening using PSA tests and/or DRE and an educational session on PCa. Of these men, 277 completed PCa-related knowledge surveys before and after viewing an educational video. Significant between-group differences in PCa-related knowledge were found at pre-assessment (p < 0.001) but not at post-assessment (p = 0.11), at which time all groups showed improved PCa-related knowledge. Most participants (77.9%) had never received PCa screening, but Vietnamese men had the lowest previous screening rate (17.3%). Chinese men had elevated PSA values and the highest abnormal DRE rates. Of the 125 men with abnormal screening outcomes, only 15.2% had adequate follow-up. Of the 144 men diagnosed with PCa in POP, 11.1% were Asians (seven Chinese, six Vietnamese, and three South Asian). Despite the ethnic heterogeneity among Asian men, a community outreach program may successfully enhance their PCa-related knowledge.

Impact of race and ethnicity on features and outcome of ductal carcinoma in situ of the breast.

BACKGROUND: The impact of race and ethnicity on the biologic features and outcome variables of women who are diagnosed with preinvasive breast cancer-ductal carcinoma in situ (DCIS)-has not been addressed widely in the published literature. METHODS: Patient demographic, clinical, and pathologic features and outcome variables were analyzed with respect to the patient's initial self-reported race/ethnicity among women who received treatment for a diagnosis of pure DCIS from 1996 to 2009. RESULTS: Of 1902 patients, 1411 were white (74.2%), 214 were African American (11.3%), 175 were Hispanic (9.1%), and 102 were Asian/Pacific Islander (5.4%). The majority of patients were between ages 41 and 70 years (83%). Patients of Hispanic and Asian/Pacific Islander descent were significantly younger than white and African American patients (P < .001). DCIS size and grade, the presence of necrosis, and the frequency of breast-conserving surgery did not differ significantly between groups. African American patients aged >70 years and Hispanic patients aged <50 years were significantly more likely to have estrogen receptor-positive DCIS than patients of other races in the same age categories (P < .001). Adjuvant radiotherapy and tamoxifen were received significantly less often by white women (P < .001). At a median follow-up of 4.8 years (range, 1-14 years), recurrence rates and the development of contralateral breast cancer did not differ significantly among racial/ethnic groups when stratified by treatments received. CONCLUSIONS: There was variation in age at presentation, biologic features, and treatment of DCIS among the different ethnic groups. Additional studies with larger numbers of ethnic minority patients are needed to confirm whether the consistent application of evidence-based treatment practices presents an opportunity for reducing disparities in patients with DCIS.

Associations among physical activity, body mass index, and health-related quality of life by race/ethnicity in a diverse sample of breast cancer survivors.

BACKGROUND: Health-related quality of life (HRQOL), body mass index (BMI), and physical activity (PA) levels have all been associated with prognosis following breast cancer and may explain partially the higher mortality for breast cancer in certain racial/ethnic subgroups. In this study, associations between PA, BMI, and HRQOL by race were examined in a sample of breast cancer survivors. METHODS: Measures of PA, BMI, and HRQOL as well as demographic and medical characteristics of women (N = 3013, 13% nonwhite) who participated in the Women's Healthy Eating and Living Study were assessed at baseline. Analysis of covariance was used to examine the relationship between PA and obesity with HRQOL outcomes. Statistical tests were 2-sided. RESULTS: African American women were less likely to meet guidelines for PA and more likely to be obese than women from other ethnic groups (P < .05). In adjusted models, women who met guidelines for PA reported significantly higher physical health composite (point differences ranged from 10.5 to 21.2 points, all P < .05) and vitality (point differences ranged from 9.9 to 16.5 points, all P < .05) scores than those who did not, regardless of race/ethnicity. Associations between obesity and HRQOL were mixed with fewer associations for Asian American and African American women and stronger associations for whites. CONCLUSIONS: Breast cancer survivors from racially and ethnically diverse populations have lower levels of PA and higher rates of obesity that are generally associated with poorer HRQOL. Culturally sensitive PA and weight loss interventions may improve these lifestyle characteristics and result in improved HRQOL.

A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors.

OBJECTIVE: Few studies have examined the dietary habits of ovarian cancer survivors. Therefore, we conducted a study to assess the feasibility and impact of two dietary interventions for ovarian cancer survivors. METHODS: In this randomized, parallel-group study, 51 women (mean age, 53 years) diagnosed with stages II-IV ovarian cancer were recruited and randomly assigned to a low fat, high fiber (LFHF) diet or a modified National Cancer Institute diet supplemented with a soy-based beverage and encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid and tocopherol levels, dietary intake, anthropometry, and health-related quality of life (HRQOL) were assessed with paired t-tests. RESULTS: The recruitment rate was 25%, and the retention rate was 75% at 6 months. At baseline, 28% and 45% of women met guidelines for intake of fiber and of fruits and vegetables, respectively. After 6 months, total serum carotenoid levels and α- and ß-carotene concentrations were significantly increased in both groups (P<0.01); however, ß-carotene concentrations were increased more in the FVJC group. Serum ß-cryptoxanthin levels, fiber intake (+5.2g/day), and daily servings of juice (+0.9 servings/day) and vegetables (+1.3 servings/day) were all significantly increased in the LFHF group (all P<0.05). Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P<0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed. CONCLUSION: Overall, this study supports the feasibility of designing dietary interventions for stages II-IV ovarian cancer survivors and provides preliminary evidence that a low fat high fiber diet and a diet supplemented with encapsulated FVJC may increase phytonutrients in ovarian cancer survivors.

The role of patient navigators in eliminating health disparities.

Despite many important efforts to increase equity in the US health care system, not all Americans have equal access to health care-or similar health outcomes. With the goal of lowering costs and increasing accessibility to health care, the nation's new health care reform legislation includes certain provisions that expand health insurance coverage to uninsured and underinsured populations, promote medical homes, and support coordination of care. These provisions may help narrow existing health care disparities. Many of the most vulnerable patients, however, may continue to have difficulty accessing and navigating the complex US health care delivery system. This article explores the unique role that patient navigation can play in improving health outcomes for racial and ethnic minorities, as well as other underserved populations, in the context of a changing healthcare environment. Patient navigators can not only facilitate improved health care access and quality for underserved populations through advocacy and care coordination, but they can also address deep-rooted issues related to distrust in providers and the health system that often lead to avoidance of health problems and non-compliance with treatment recommendations. By addressing many of the disparities associated with language and cultural differences and barriers, patient navigators can foster trust and empowerment within the communities they serve. Specific patient navigator activities are discussed, and metrics to evaluate program efforts are presented.

Was race a factor in the outcomes of the Women's Health Eating and Living Study?

BACKGROUND: The objective of this study was to determine whether women who were participating in the Women's Healthy Eating and Living (WHEL) Study exhibited similar dietary changes, second breast cancer events, and overall survival regardless of race/ethnicity. METHODS: For this secondary analysis, the authors used data from 3013 women who were self-identified as Asian American, African American, Hispanic, or white and who were assigned randomly to a dietary intervention or a comparison group. Changes in dietary intake over time by race/ethnicity and intervention status were examined using linear mixed-effects models. Cox proportional hazards models were used to examine the effects of the intervention on the occurrence of second breast cancer events and overall survival. Statistical tests were 2-sided. RESULTS: African Americans and Hispanics consumed significantly more calories from fat (+3.2%) and less fruit (-0.7 servings daily) than Asians and whites at baseline (all P < .01). Overall, intervention participants significantly improved their dietary pattern from baseline to the end of Year 1, reducing calories from fat by 4.9% and increasing intake of fiber (+6.6 grams daily), fruit (+1.1 servings daily), and vegetables (+1.6 servings daily; all P < .05). Despite improvements in the overall dietary pattern of these survivors, the intervention did not significantly influence second breast cancer events or overall survival. CONCLUSIONS: Overall, all racial groups significantly improved their dietary pattern over time, but the maintenance of these behaviors were lower among African-American women. More research and larger minority samples are needed to determine the specific factors that improve breast cancer-specific outcomes in diverse populations of survivors.

Poor physical health predicts time to additional breast cancer events and mortality in breast cancer survivors.

BACKGROUND: Health-related quality of life has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors. METHODS: Women with early-stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association. RESULTS: There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01-10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psychosocial variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher body mass index, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all). CONCLUSION: Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.

Health and healthcare perspectives of African American residents of an unincorporated community: a qualitative assessment.

Residential perspectives about health in unincorporated communities are virtually unexplored. In this study, we conducted focus groups to assess individual and community health status, environmental health mediators, and systematic barriers to healthcare among African American residents of the unincorporated town, Fresno, Texas. Residents described their individual health status as excellent, but depicted the community's health status as fair. Unaffordable healthcare, limited access to healthcare, and environmental mediators were perceived to impact the Fresno community's health status. Our findings suggest a need to begin to examine health outcomes for minority residents in other unincorporated communities.

A Pilot Study Evaluating Organochlorine and Organophosphate Pesticide Exposure in Children and Adolescents of Mexican Descent Residing in Hidalgo County, Texas.

Children and adolescents of Mexican descent residing in Hidalgo County (TX) were evaluated for exposure to organochlorine (OC) and organophosphate (OP) pesticides. A convenience sample of 60 participants enrolled in our pilot study. The lipid-adjusted serum concentrations of nine OC metabolites and creatinine-adjusted urinary concentrations of six OP metabolites were measured and compared with data from the Centers for Disease Control and Prevention's Fourth Report on Human Exposure to Environmental Chemicals. Descriptive statistics were used to summarize the concentration levels for each metabolite. Study participants were aged 5-18 years. For most of the OC and OP metabolites, our findings showed that participants had concentration levels within the distributional range of the national data. However, notable outlying levels (greater than the 95th percentile in the Fourth Report) were identified for the following OC metabolites: gamma-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethene, and p,p'-dichlorodiphenyltrichloroethane. Among the children aged 5-11 years, one child had an outlying value for the OP metabolite: dimethylphosphate. Our findings on the levels of OC and OP pesticide exposure enhances the credibility of national estimates, and can serve as baselines for children and adolescents of Mexican descent residing in Lower Rio Grande Valley. Furthermore, our study contributes to the lacunae of knowledge regarding environmental exposures and presses further investigation of outlying OC and OP exposure levels.

Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer.

Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.

Comparison of baseline dietary intake of Hispanic and matched non-Hispanic white breast cancer survivors enrolled in the Women's Healthy Eating and Living study.

OBJECTIVE: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. DESIGN: Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. SUBJECTS: One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. STATISTICAL ANALYSES: Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. RESULTS: Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. CONCLUSIONS: There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival.

The Utility of a Connecting Framework to Facilitate Understanding of and Reduce the Disparities in Hospice Care Experienced by Racial and Ethnic Minorities.

Rapidly changing demographics in the United States and diverse cultural beliefs impact hospice utilization and end-of-life care. Healthcare professionals and clinicians need a connecting framework to understand patients' and their family's perspectives regarding utilization of those services. This framework will assist healthcare workers in providing culturally sensitive and appropriate information to patients nearing the end of life, so that they and their loved ones can make informed decisions for optimal care during this passage of life. Considering the variables in this framework may also help facilitate communication between healthcare professionals and patients and reduce misunderstanding among the surviving family members.

Ambivalence: A Key to Clinical Trial Participation?

Trust exerts a multidimensional influence at the interpersonal level in the clinical trials setting. Trust and distrust are dynamic states that are impacted, either positively or negatively, with each participant-clinical trials team interaction. Currently, accepted models of trust posit that trust and distrust coexist and their effects on engagement and retention in clinical trials are mediated by ambivalence. While understanding of trust has been informed by a robust body of work, the role of distrust and ambivalence in the trust building process are less well understood. Furthermore, the role of ambivalence and its relationship to trust and distrust in the clinical trials and oncology settings are not known. Ambivalence is a normal and uncomfortable state in the complex decision making process that characterizes the recruitment and active treatment phases of the clinical trials experience. The current review was conducted to understand the constructs of ambivalence as a mediator of trust and distrust among vulnerable, minority participants through different stages of the oncology clinical trials continuum, its triggers and the contextual factors that might influence it in the setting of minority participation in oncology clinical trials. In addition, the researchers have sought to link theory to clinical intervention by investigating the feasibility and role of Motivational Interviewing in different stages of the clinical trials continuum. Findings suggest that ambivalence can be processed and managed to enable a participant to generate a response to their ambivalence. Thus, recognizing and managing triggers of ambivalence, which include, contradictory goals, role conflicts, membership dualities, and supporting participants through the process of reducing ambivalence is critical to successfully managing trust. Contextual factors related to the totality of one's previous health-care experience, specifically among the marginalized or vulnerable, can contribute to interpersonal ambivalence. In addition, changes in information gathering as a moderator of interpersonal ambivalence may have enormous implications for gathering, assessing, and accepting health information. Finally, motivational Interviewing has widespread applications in healthcare settings, which includes enabling participants to navigate ambivalence in shared-decision making with their clinician, as well as executing changes in participant behavior. Ultimately, the Integrated Model of Trust can incorporate the role of therapeutic techniques like Motivational Interviewing in different stages of the clinical trials continuum. Ambivalence is a key component of clinical trial participation; like trust, ambivalence can be managed and plays a major role in the management of trust in interpersonal relationships over time. The management of ambivalence may play a major role in increasing clinical trial participation particularly among the marginalized or the vulnerable, who may be more susceptible to feelings of ambivalence.

Novel natural immunogenic peptides from Numb1 and Notch1 proteins for CD8+ cells in ovarian ascites.

Notch is a plasma membrane receptor involved in the control of cell fate specification and in the maintenance of the balance between proliferation and differentiation in many cell lineages. Disruption of Notch has been implicated in a variety of hematological and solid cancers. Numb is also expressed in many adult mammalian cells. Adult cells divide symmetrically, and Numb is symmetrically partitioned at mitosis. The Numb-mediated regulation of Notch is believed to play a causative role in naturally occurring breast cancers. Reduction of Numb levels in breast tumors is regulated by proteasomal degradation. We reasoned that if the disregulated negative control of Notch by Numb protein is the consequence of Numb proteasomal degradation, then degradation of Numb can generate peptides which are transported, presented by MHC-I molecules. Surprisingly we found few candidate naturally processed peptides from Notch1, Notch2, and Numb1. CD8+ T cells expressing TCRs which specifically recognized peptides Notch1 (2112-2120) and Numb1 (87-95) were presented in the ascites of ovarian cancer patients. Many of these cells were differentiated and expressed high levels of Perforin. The natural immunogenicity of Notch1 and particularly of Numb1 suggests a mechanism of immunosurveillance which is overcome during tumor progression. Immunotherapy with tumor antigens from Notch and Numb should be important for treatment of cancer patients.

Is the MEDFICTS rapid dietary fat screener valid for premenopausal African-American women?

OBJECTIVE: To assess the predictive validity of the meats, eggs, dairy, fried foods, fat in baked goods, convenience foods, fats added at the table, and snacks (MEDFICTS) questionnaire, a rapid dietary fat screening instrument, when used with African-American women. DESIGN: A case series design was utilized to assess the validity of MEDFICTS compared to the Arizona Food Frequency Questionnaire. SUBJECTS/SETTING: Data for this study were collected from 184 healthy premenopausal African-American women who completed both the MEDFICTS and the Arizona Food Frequency Questionnaire during screening for eligibility in a nutrition intervention study. STATISTICAL ANALYSES PERFORMED: Analyses of sensitivity, specificity, predictive values, and receiver operating characteristic analysis were used to examine the predictive validity of MEDFICTS. Covariates of correctly and incorrectly identified groups were examined with contingency table analysis and t tests. RESULTS: MEDFICTS was a statistically significant predictor of dietary fat consumption, but underestimated fat consumption of >or=30%. MEDFICTS' sensitivity to detect those consuming >or=30% fat was 57.3%, whereas its specificity (detection of those consuming <30% dietary fat) was 66.0%. Positive and negative predictive values were 80.6% and 38.5%, respectively. A reduction in the threshold score resulted in increased sensitivity but decreased specificity. Women identified by MEDFICTS as consuming <30% dietary fat but who were actually consuming 30% or more reported greater consumption of fats from foods classified as mixed foods. CONCLUSIONS: Study findings suggest MEDFICTS underestimates fat consumption of >or=30%. The inclusion of a category to assess mixed foods could improve the sensitivity and specificity of MEDFICTS for predicting dietary fat consumption. These results demonstrate the need for population-based validation of dietary screening instruments.