Extended interval dosing of natalizumab in multiple sclerosis.

BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4ß1/ß7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days. METHODS: A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks. RESULTS: 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. CONCLUSIONS: Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.

Translation of a Ski School Sun Safety Program to North American Ski and Snowboard Schools.

Health promotion programs that develop and implement strategies to promote sun safety practices to children have the potential to reduce skin cancer occurrence later in life. Go Sun Smart (GSS), a sun safety program for employees and guests of ski areas, was distributed to determine if an enhanced dissemination strategy was more effective than a basic dissemination strategy at reaching parents at ski and snowboard schools. On-site observations of GSS use and surveys of 909 parents/caregivers with children enrolled in ski and snowboard schools at 63 ski areas were conducted and analyzed using techniques for clustered designs. No differences were identified by dissemination strategy. Greater implementation of GSS (>5 messages posted) was associated with greater parental recall, 36.6% versus 16.7%, of materials, but not greater sun protection practices. Greater recall of messages, regardless of level of implementation, resulted in greater sun protection practices including applying sunscreen (p < .05), providing sunglasses and goggles (p < .01), and more use of all sun protection practices (p < .01). Ski areas with more program materials appeared to reach parents with sun safety advice and thus convinced them to take more precautions for their children. Sun safety need not be at odds with children's outdoor recreation activities.

Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. METHODS: In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. RESULTS: 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. CONCLUSIONS: Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting.

A tumor-related lymphoid progenitor population supports hierarchical tumor organization in canine B-cell lymphoma.

BACKGROUND: Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor-initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B-cell lymphoma have not been conclusively identified. HYPOTHESIS/OBJECTIVES: Tumor cells with a progenitor phenotype exist in B-cell lymphoma, reflecting a hierarchical organization. ANIMALS: Twenty-eight client-owned dogs with previously untreated B-cell lymphoma and 6 healthy dogs. METHODS: This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B-cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL-2Rγ(-/-) mice was adapted to expand and serially transplant primary canine B-cell lymphoma. RESULTS: LPCs were expanded in lymph nodes from 28 dogs with B-cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B-cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest the presence of a hierarchy of tumor cells in B-cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.

Interferon ß-1b and glatiramer acetate effects on permanent black hole evolution.

OBJECTIVE: To compare interferon ß-1b (IFNß-1b) and glatiramer acetate (GA) on new lesion (NL) (gadolinium-enhancing, new T2) evolution into permanent black holes (PBH)--a marker of irreversible tissue damage--in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: BEYOND was a large, phase III, clinical trial comparing IFNß-1b 250 µg, IFNß-1b 500 µg, and GA (2:2:1). Patient scans were reexamined post hoc for PBH in a rater-blinded manner. Two predefined coprimary endpoints compared IFNß-1b 250 µg with GA: first, number of PBH per patient at year 2 evolving from year 1 NL, then proportion of year 1 NL evolving into PBH at year 2. IFNß-1b 500 µg and GA were compared in an exploratory fashion. RESULTS: Approximately 90% (1,957/2,244) of patients had NL at year 1 with follow-up at year 2. Mean numbers of PBH per patient at year 2 evolving from year 1 NL were lower for IFNß-1b 250 µg than GA (0.30 vs 0.43; p = 0.0451). The proportion of NL evolving into PBH was similar (IFNß-1b 250 µg vs GA: 21.6% vs 23.5%; p > 0.20). For IFNß-1b 500 µg, both the mean PBH number per patient at year 2 evolving from year 1 NL (0.26 vs 0.43; p = 0.0037) and proportion of NL evolving into PBH (16.3% vs 23.5%; p = 0.0409) were lower relative to GA. CONCLUSION: IFNß-1b affected PBH development to a similar or better extent than GA. IFNß-1b favorably influences an MRI outcome indicative of permanent tissue destruction in the brains of patients with multiple sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IFNß-1b is associated with a reduction in MRI PBH formation and evolution compared with GA between years 1 and 2 of treatment.

Association between comorbidity and clinical characteristics of MS.

BACKGROUND: Comorbidity may be associated with the clinical phenotype of disease and may affect prognostication and treatment decisions. Using the North American Research Committee on Multiple Sclerosis Registry, we described comorbidities present at onset and diagnosis of multiple sclerosis (MS) and examined whether comorbidities present at onset were associated with clinical course or age of MS symptom onset. METHODS: In 2006, 8983 participants reported their physical and mental comorbidities; smoking status; height; and past and present weight. We compared clinical course at onset and age of symptom onset by comorbidity status. RESULTS: At MS onset, a substantial proportion of participants had physical (24%) or mental (8.4%) comorbidities. The mean (SD) age of MS onset was 31.2 (9.0) years. Vascular, autoimmune, cancer, visual, and musculoskeletal comorbidities were associated with a later age of symptom onset. Among men and women, the odds of a relapsing course at onset were increased if mental comorbidities (OR 1.48; 1.08-2.01) were present at symptom onset. In women, gastrointestinal comorbidities (OR 1.78; 1.25-2.52) and obesity (OR 2.08 1.53-2.82) at MS onset were also associated with a relapsing course at onset. CONCLUSIONS: Comorbidity is frequently present at onset of MS and is associated with differences in clinical characteristics.

Comorbidity delays diagnosis and increases disability at diagnosis in MS.

BACKGROUND: Comorbidity is common in the general population and is associated with adverse health outcomes. In multiple sclerosis (MS), it is unknown whether preexisting comorbidity affects the delay between initial symptom onset and diagnosis ("diagnostic delay") or the severity of disability at MS diagnosis. OBJECTIVES: Using the North American Research Committee on Multiple Sclerosis Registry, we assessed the association between comorbidity and both the diagnostic delay and severity of disability at diagnosis. In 2006, we queried participants regarding physical and mental comorbidities, including date of diagnosis, smoking status, current height, and past and present weight. Using multivariate Cox regression, we compared the diagnostic delay between participants with and without comorbidity at diagnosis. We classified participants enrolled within 2 years of diagnosis (n = 2,375) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with comorbidity using polytomous logistic regression. RESULTS: The study included 8,983 participants. After multivariable adjustment for demographic and clinical characteristics, the diagnostic delay increased if obesity, smoking, or physical or mental comorbidities were present. Among participants enrolled within 2 years of diagnosis, the adjusted odds of moderate as compared to mild disability at diagnosis increased in participants with vascular comorbidity (odds ratio [OR] 1.51, 95% CI 1.12-2.05) or obesity (OR 1.38, 95% CI 1.02-1.87). The odds of severe as compared with mild disability increased with musculoskeletal (OR 1.81, 95% CI 1.25-2.63) or mental (OR 1.62, 95% CI 1.23-2.14) comorbidity. CONCLUSIONS: Both diagnostic delay and disability at diagnosis are influenced by comorbidity. The mechanisms underlying these associations deserve further investigation.

High frequency of adverse health behaviors in multiple sclerosis.

BACKGROUND: Health behaviors influence chronic disease risks in the general population, and may influence health outcomes independently of comorbid diseases. Health behaviors receive less attention in multiple sclerosis (MS) than in the general population. We assessed health behaviors among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the demographic characteristics associated with particular health behaviors. METHODS: In October 2006, we surveyed NARCOMS participants regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; physical activity using questions from the PEPI study, alcohol use using the AUDIT-C; and height and weight. To determine the independent demographic predictors of health behaviors, we used multivariable logistic regression, either binary or polytomous as appropriate. RESULTS: Of 8983 responders, 4867 (54.2%) ever smoked; 1542 (17.3%) currently smoked. On the basis of the AUDIT-C, 1632 (18.2%) were at risk for alcohol abuse or dependence. A quarter of participants were obese (n = 2269), and 2780 (31.3%) were overweight. Fewer than 25% of participants reported moderate or heavy leisure-time physical activity. Generally, lower socioeconomic status was associated with a higher frequency of adverse health behaviors accounting for other demographic factors. With increasing levels of disability, the reported intensity of physical activity was lower, and the frequency of overweight or obesity was higher. CONCLUSIONS: Patients with MS exhibit frequent adverse health behaviors, increasing the risk of other chronic diseases. Further research is needed to determine how these behaviors influence disability progression, quality of life, and other MS-related outcomes.

Comorbidity, socioeconomic status and multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is associated with substantial morbidity. The impact of comorbidity on MS is unknown, but comorbidity may explain some of the unpredictable progression. Comorbidity is common in the general population, and is associated with adverse health outcomes. To begin understanding the impact of comorbidity on MS, we need to know the breadth, type, and frequencies of comorbidities among MS patients. Using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry, we aimed to describe comorbidities and their demographic predictors in MS. METHODS: In October 2006, we queried NARCOMS participants regarding physical comorbidities. Of 16,141 participants meeting the inclusion criteria, 8983 (55.7%) responded. RESULTS: Comorbidity was relatively common; if we considered conditions which are very likely to be accurately self-reported, then 3280 (36.7%) reported at least one physical comorbidity. The most frequently reported comorbidities were hypercholesterolemia (37%), hypertension (30%), and arthritis (16%). Associated with the risk of comorbidity were being male [females vs. males, odds ratio (OR) 0.77; 0.69-0.87]; age (age >60 years vs. age < or = 44 years, OR 5.91; 4.95-7.06); race (African Americans vs. Whites, OR 1.46; 1.06-2.03); and socioeconomic status (Income <$15,000 vs. Income >$100,000, OR 1.37; 1.10-1.70). CONCLUSIONS: Comorbidity is common in MS and similarly associated with socioeconomic status.

Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-cell lymphoma.

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.

Competing demands in the office visit: what influences mammography recommendations?

BACKGROUND: The multiple competing demands of the busy office visit have been shown to interfere with delivery of preventive services. In this study we used physician recommendations for screening mammography to examine the relative importance of physician, patient, and visit characteristics in determining on which patient visits this preventive service will be provided. METHODS: Physicians in the Ambulatory Sentinel Practice Network (ASPN) completed a questionnaire describing their knowledge, attitudes, and beliefs about screening mammography. They also described the content of a series of nonacute care visits with women aged 40 to 75 years with regard to making a recommendation when the patient was due for screening mammography. The data were linked, and univariate and multivariate logistic regression methods were used to examine the relative importance of physician, patient, and visit characteristics on making a recommendation for mammography. RESULTS: Ninety-three physicians reported making a recommendation for screening mammography on 53.1% of nonacute visits. When modeling physician, patient, and visit characteristics separately, 70% of the variability in the model is explained by physician characteristics only, 63% by patient characteristics only, and 73% by visit characteristics only. A combined model using all characteristics explained 85% of the variability. CONCLUSIONS: Although characteristics of physicians and patients can predict frequency of recommendations for mammography, the specific characteristics of the visit are equally important. Efforts to improve delivery of preventive services in primary care that emphasize physician education and performance feedback are unlikely to increase rates of mammography recommendation. Effective strategies must consider the multiple competing demands faced by patients and physicians during each office visit and seek ways for assisting them in setting rational priorities for services.

Rates and causes of disagreement in interpretation of full-field digital mammography and film-screen mammography in a diagnostic setting.

OBJECTIVE: This study was performed to determine the rates and causes of disagreements in interpretation between full-field digital mammography and film-screen mammography in a diagnostic setting. SUBJECTS AND METHODS: Patients undergoing diagnostic mammography were invited to participate in the digital mammography study. Three views, selected by the radiologist interpreting the film-screen mammography, were obtained in both film-screen mammography and digital mammography. Radiologists independently assigned a Breast Imaging Reporting and Data System (BI-RADS) category to the film-screen mammography and the digital mammography images. The BI-RADS categories were grouped into the general categories of agreement, partial agreement, or disagreement. A third and different radiologist reviewed all cases of disagreement, reached a decision as to management, and determined the primary cause of disagreement. RESULTS: Six radiologists reviewed digital mammography and film-screen mammography diagnostic images in a total of 1147 breasts in 692 patients. Agreement between digital mammography and final film-screen mammography assessment was present in 937 breasts (82%), partial agreement in 159 (14%), and disagreement in 51 (4%), for a kappa value of 0.29. The primary causes of disagreement were differences in management approach of the radiologists (52%), information derived from sonography or additional film-screen mammograms (34%), and technical differences between the two mammographic techniques (10%). CONCLUSION: Significant disagreement between film-screen mammography and digital mammography affecting follow-up management was present in only 4% of breasts. The most frequent cause of disagreement in interpretation was a difference in management approach between radiologists (interobserver variability). This source of variability was larger than that due to differences in lesion visibility between film-screen mammography and digital mammography.

Comparison of full-field digital mammography with screen-film mammography for cancer detection: results of 4,945 paired examinations.

PURPOSE: To prospectively compare full-field digital mammography (FFDM) with screen-film mammography (SFM) for cancer detection in a screening population. MATERIALS AND METHODS: At two institutions, 4,945 FFDM examinations were performed in women aged 40 years and older presenting for SFM. Two views of each breast were acquired with each modality. SFM and FFDM images were interpreted independently. Findings detected with either SFM or FFDM were evaluated with additional imaging and, if warranted, biopsy. RESULTS: Patients in the study underwent 152 biopsies, which resulted in the diagnosis of 35 breast cancers. Twenty-two cancers were detected with SFM and 21 with FFDM. Four were interval cancers that became palpable within 1 year of screening and were considered false-negative findings with both modalities. The difference in cancer detection rate was not significant. FFDM had a significantly lower recall rate (11.5%; 568 of 4,945) than SFM (13.8%; 685 of 4,945) (P <.001, McNemar chi(2) model; P <.03, generalized estimating equations model). The positive biopsy rate for findings detected with FFDM (30%; 21 of 69) was higher than that for findings detected with SFM (19%; 22 of 114), but this difference was not significant. CONCLUSION: No difference in cancer detection rate has yet been observed between FFDM and SFM. FFDM has so far led to fewer recalls than SFM.

Performance of screening mammography among women with and without a first-degree relative with breast cancer.

BACKGROUND: Although it is recommended that women with a family history of breast cancer begin screening mammography at a younger age than average-risk women, few studies have evaluated the performance of mammography in this group. OBJECTIVE: To compare the performance of screening mammography in women with a first-degree family history of breast cancer and women of similar age without such history. DESIGN: Cross-sectional. SETTING: Mammography registries in California (n = 1), New Hampshire (n = 1), New Mexico (n = 1), Vermont (n = 1), Washington State n = 2), and Colorado (n = 1). PARTICIPANTS: 389 533 women 30 to 69 years of age who were referred for screening mammography from April 1985 to November 1997. MEASUREMENTS: Risk factors for breast cancer; results of first screening examination captured for a woman by a registry; and any invasive cancer or ductal carcinoma in situ identified by linkage to a pathology database, the Surveillance, Epidemiology, and End Results program, or a state tumor registry. RESULTS: The number of cancer cases per 1000 examinations increased with age and was higher in women with a family history of breast cancer than in those without (3.2 vs. 1.6 for ages 30 to 39 years, 4.7 vs. 2.7 for ages 40 to 49 years, 6.6 vs. 4.6 for ages 50 to 59 years, and 9.3 vs. 6.9 for ages 60 to 69 years). The sensitivity of mammography increased significantly with age (P = 0.001 [chi-square test for trend]) in women with a family history and in those without (63.2% [95% CI, 41. 5% to 84.8%] vs. 69.5% [CI, 57.7% to 81.2%] for ages 30 to 39 years, 70.2% [CI, 61.0% to 79.5%] vs. 77.5% [CI, 73.3% to 81.8%] for ages 40 to 49 years, 81.3% [CI, 73.3% to 89.3%] vs. 80.2% [CI, 76.5% to 83.9%] for ages 50 to 59 years, and 83.8% [CI, 76.8% to 90.9%] vs. 87.7% [CI, 84.8% to 90.7%] for ages 60 to 69 years). Sensitivity was similar for each decade of age regardless of family history. The positive predictive value of mammography was higher in women with a family history than in those without (3.7% vs. 2.9%; P = 0.001). CONCLUSIONS: Cancer detection rates in women who had a first-degree relative with a history of breast cancer were similar to those in women a decade older without such a history. The sensitivity of screening mammography was influenced primarily by age.

Validity of self-reported colorectal cancer screening behavior.

End points for trials promoting cancer screening are often based on self-reported screening behavior. This study was designed to evaluate and optimize the reliability of a computer-assisted telephone interview for collecting self-reported colorectal cancer screening behavior. Cases who had received a fecal occult blood test (FOBT), flexible sigmoidoscopy, and/or colonoscopy, and controls who had no record of colorectal screening were identified among 40-75-year-old members of the Denver Kaiser Permanente Health Care Program and were contacted by telephone. Sensitivities and specificities of self-reported screening were calculated by comparison of subjects' recall with Kaiser Permanente records. The questionnaire was revised based upon results of the pilot phase of the study. Using the revised questionnaire, the sensitivity of self-reported screening was 96.2% for the FOBT, 94.9% for flexible sigmoidoscopy, 88.7% for colonoscopy, and 96.2% for either endoscopic screening test. The specificity of self-reported screening was 85.9% for the FOBT, 92.2% for flexible sigmoidoscopy, 96.8% for colonoscopy, and 92.0% for either endoscopic screening test. No marked differences in the accuracy of the self-reports were detected as a function of gender, age, ethnicity, or family history of colorectal cancer of the participants. Self-reports of colon cancer screening behavior can be reliably used as end points for intervention trials when carefully phrased questions are used.

Practice patterns of family physicians in practice-based research networks: a report from ASPN. Ambulatory Sentinel Pratice Network.

BACKGROUND: Practice-based research networks are growing and undertaking larger and more complex studies to inform the clinical practice of family physicians. We describe a study that compares clinical behaviors of physicians in the Ambulatory Sentinel Practice Network (ASPN), a large national practice-based research network, with those from the National Ambulatory Medical Care Survey (NAMCS). METHODS: A survey, replicating NAMCS, was conducted among 129 family physician members of ASPN. Nested logistic regression was used to determine which services could predict ASPN membership after adjustment for common and easily observed patient and physician characteristics. RESULTS: Of 20 specific patient services, only 4 were predictive of membership in ASPN. Of these 4, 2 were screening or diagnostic services; ASPN physicians were 1.18 times more likely to obtain a blood pressure measurement and 0.60 times as likely to order a culture for streptococcal pharyngitis. ASPN physicians were 2.30 times more likely to provide family planning counseling and 1.66 times more likely to provide smoking cessation counseling after adjusting for patient smoking status. CONCLUSIONS: We conclude that there are minimal differences in the practice patterns of family physicians participating in a large national practice-based research network and those included in the probability sample of NAMCS. Additional work is needed to examine further those characteristics of the phenomena observed in practice-based research network research that might affect generalizability of results to the larger community of practicing family physicians.

Promoting cancer screening among the first-degree relatives of breast and colorectal cancer patients: the design of two randomized trials.

BACKGROUND: In this paper two large nationwide trials are described, both of which will test a comparable telephone-based counseling intervention to promote cancer screening among the first-degree relatives (FDRs) of breast and colorectal cancer patients. The unit of randomization will be the family unit of eligible FDRs. Access to FDRs will be obtained from their relatives with cancer. Selected intervention and design issues are reviewed, including how both projects will respond to FDRs who exhibit significant levels of cancer-specific anxiety or distress and how potential high-risk cancer families will be accommodated. METHODS: Pursuant to the development of both studies, two feasibility surveys were conducted to determine whether patients would grant access to their FDRs and whether the FDRS identified by these patients would be receptive to the telephone intervention. RESULTS: Approximately 80% (106 of 132) of breast cancer patients agreed to provide access to their eligible FDRs when contacted on-site at participating hospitals and clinics. Of those subsequently selected for telephone follow-up (n = 95 or 90%), 80% (n = 76) were successfully contacted by telephone, and of these 97% (n = 74) provided the names and telephone numbers of their FDRs. Among colorectal cancer patients contacted on-site (n = 46), 96% (n = 44) agreed to provide access to their FDRs, and of those contacted by telephone (n = 33 or 75%), 91% (n = 30) provided the requested information about their FDRs. Once contacted, 95% of breast cancer FDRs (55 of 58) and 91% of colorectal cancer patients (51 of 56) endorsed the intervention strategy. CONCLUSIONS: It is argued that this intervention, if proven effective, could provide an exportable strategy for reaching large numbers of high-risk individuals to promote cancer screening.

A study of the relationship between family history of breast cancer and knowledge of breast cancer genetic testing prerequisites.

Awareness of hereditary breast cancer genetic testing, of breast cancer risk factors, and of increased level of risk based on family history are necessary before women can seek out genetic services. The aim of this paper is to describe the relationships between family history of breast cancer and awareness of genetic testing, knowledge of breast cancer risk factors, and perceived lifetime risk of breast cancer. An anonymous survey was administered by mail to a random sample of 600 women, 200 from each of three breast cancer family history groups (none, intermediate, and strong), drawn from a population-based registry of 240,000 women enrolled in a mammography screening program in the Denver Metropolitan area in Colorado. Awareness of genetic testing for breast cancer risk assessment was found to be significantly associated with family history of breast cancer, increasing from 35% in the lowest family history risk group to 67% in the group with the strongest familial risk (p = 0.002). In all family history groups, nearly 70% of respondents viewed high-fat diet and smoking as being important in relation to breast cancer risk, but alcohol was seen as being only somewhat important or not important by almost half of all respondents. Having a mother or sister with breast cancer was reported as being extremely or very important by nearly all respondents, regardless of family history. As expected, perceived lifetime risk for developing breast cancer was associated with family history (p = 0.001), but the perception of the lifetime risk for breast cancer was much higher among all of the family history groups than their true risk. In conclusion, educational interventions are needed to heighten women's awareness of genetic testing, to clarify women's knowledge of breast cancer risk factors, especially alcohol, and to reassure many women that their actual breast cancer risk is lower than they might perceive.