Understanding the characteristics of early and late survey responders has implications for recruitment efforts and for informing potential response bias. The main objective of this analysis was to examine survey responder status (ie, early vs late response) by sociodemographic characteristics and by salience of study variables among respondents.
We analyzed data from a survey on family cancer history and perceived cancer risk among women at a large managed health-care organization. For baseline and 12-month follow-up surveys, we defined early versus late responder status according to the 95th percentile of the number of days it took to obtain completed interviews.
We found no significant associations between responder status and sociodemographic characteristics at baseline or follow-up. At baseline, early responders were significantly more likely than late responders to have a personal history of breast cancer (5.2% vs 3.4%, P = .04) and to have been referred for genetic counseling (4.6% vs 2.0%, P = .004). The association between personal history of breast cancer and responder status persisted at follow-up; only 3.5% of late responders at baseline were also late responders at follow-up. Follow-up survey nonresponse rates did not vary by baseline responder status.
Survey topic salience is associated with early response and is important for recruitment. However, once recruited, late responders do not remain late responders at follow-up, suggesting that extra efforts made to recruit late responders are worthwhile. Health-related agencies that conduct surveys should consider survey salience in survey administration and recruitment strategies.
Evidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing.
An ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate).
Among the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0–9.6) to report genetic counseling referral.
In a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing.
BRCA1 and BRCA2 genes; family history; genetic counseling; genetic testing; hereditary breast and ovarian cancer syndrome
To examine when and why women disbelieve tailored information about their risk of developing breast cancer.
690 women participated in an online program to learn about medications that can reduce the risk of breast cancer. The program presented tailored information about each woman’s personal breast cancer risk. Half of women were told how their risk numbers were calculated, whereas the rest were not. Later, they were asked whether they believed that the program was personalized, and whether they believed their risk numbers. If a woman did not believe her risk numbers, she was asked to explain why.
Beliefs that the program was personalized were enhanced by explaining the risk calculation methods in more detail. Nonetheless, nearly 20% of women did not believe their personalized risk numbers. The most common reason for rejecting the risk estimate was a belief that it did not fully account for personal and family history.
The benefits of tailored risk statistics may be attenuated by a tendency for people to be skeptical that these risk estimates apply to them personally.
Decision aids may provide risk information that is not accepted by patients, but addressing the patients’ personal circumstances may lead to greater acceptance.
Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and its impact on treatment decisions for women diagnosed with breast cancer.
Study aims were to assess use of HER2 testing, to describe characteristics of patients who do or do not receive HER2 testing, to describe which HER2 tests were used (fluorescence in situ hybridization [FISH] or immunohistochemistry [IHC]), and to evaluate trastuzumab use as a function of HER2 results.
The population included 6,460 women diagnosed with invasive breast cancer between 1999 and 2007 at eight geographically distributed Cancer Research Network health care delivery systems in the United States.
Electronic records were used to identify patient and tumor characteristics and treatment with trastuzumab, and chart abstraction was performed for 400 women (50 per site) to identify receipt of HER2 testing and results.
Over 90% of study participants received HER2 testing. Everyone who received trastuzumab had a HER2 test, and nearly all (>95%) who received trastuzumab had a positive HER2 test result recorded in their medical chart. Most (77%) eligible cases with a positive HER2 test result diagnosed after 2005 received trastuzumab. This study expands upon previous work in individual health plans.
HER2 status has been successfully incorporated into medical practice to guide treatment decisions for breast cancer patients in diverse integrated health care delivery settings.
herceptin; trastuzumab; pharmacogenomics; her2neu; breast cancer
Risk perceptions and disease worry of 1,959 healthy adults were measured in a telephone-based survey. In the model for each of eight health conditions, people’s perceived risk was related to their worry for that condition (p < .0001) and their worry for the other seven conditions (p < .001). There was also an interaction indicating that the less people were worried about a certain condition, the more their worry about the other seven conditions increased their risk perception for that condition (p < .0001). The results are important for preventing biased risk perceptions in multiple-disease contexts.
Disease risk; disease worry; affect heuristic; genetic testing
The aim of the current study was to learn how people integrate attitudes about multiple health conditions to make a decision about genetic testing uptake.
This study recruited 294 healthy young adults from a parent research project, the Multiplex Initiative, conducted in a large health care system in Detroit, Michigan. All participants were offered a multiplex genetic test that assessed risk for 8 common health conditions (e.g., type 2 diabetes). Data were collected from a baseline survey, a web-based survey, and at the time of testing.
Averaging attitudes across diseases predicted test uptake but did not contribute beyond peak attitudes, the highest attitude toward testing for a single disease in the set. Peak attitudes were found sufficient to predict test uptake.
The effects of set size and mode of presentation could not be examined because these factors were constant in the multiplex test offered.
These findings support theories suggesting that people use representative evaluations in attitude formation. The implication of these findings for further developments in genetic testing is that the communication and impact of multiplex testing may need to be considered in the light of a bias toward peak attitudes.
cognitive psychology; judgment and decision psychology; patient choice modeling; social judgment theory
To describe the pattern and frequency of oncogene mutations in white and African American (AA) women with endometrial cancer, and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors.
Endometrial cancer patients from a large, urban hospital were identified through medical records, and representative formalin fixed paraffin embedded tumor blocks were retrieved. The study sample included 150 patients (84 AA) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay v1.0 (Sequenom), were employed to test for 238 mutations in 19 common oncogenes. Chi-square tests and Fisher’s exact tests were used to assess differences in distribution of variables by race and oncogene mutation status.
There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). The majority of mutations were found in PIK3CA (16/20). Thirteen percent of endometroid tumors harbored mutations (11 PIK3CA and 2 KRAS), as did 29% of the Malignant Mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low grade endometrioid cancers, tumors from AA patients were significantly associated with harboring either a KRAS or PIK3CA mutation (p=0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in AA women.
This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.
Quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy.
Identified all women at a Midwestern health system with initial diagnosis of AJCC stage III/IV breast cancer (1995–2003) and random sample of 50 women initially diagnosed with stage I/II who progressed to stage III/IV. Calculated rate of new cardiovascular outcomes (heart failure, dysrhythmia and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents.
Of 315 patients, 90.5% (N=285) received systemic cancer therapy; 67.7% (n=193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4% ≤ 59 years vs. 31.9% aged 70+). Adjusting for age, race, stage, surgery/radiation, ER/PR status and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared to those exposed to non-cardiotoxic drugs (adjusted hazard ratio=2.5, 95% CI 0.9, 7.2). Patients with cardiac event history (relative risk=3.2, 95% CI 2.0–5.1) and those with heart failure history (relative risk=5.9, 95% CI 2.4–14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years follow-up 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event.
Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common, treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patient’s remaining lifespan.
breast cancer; chemotherapy; cardiotoxic agents; cardiotoxicity risk
Comparative risk perceptions may rival other types of information in terms of effects on health behavior decisions.
We examined associations between comparative risk perceptions, affect, and behavior while controlling for absolute risk perceptions and actual risk.
Women at an increased risk of breast cancer participated in a program to learn about tamoxifen which can reduce the risk of breast cancer. Women reported comparative risk perceptions of breast cancer and completed measures of anxiety, knowledge, and tamoxifen-related behavior intentions. Three months later, women reported their behavior.
Comparative risk perceptions were positively correlated with anxiety, knowledge, intentions, and behavior three months later. After controlling for participants’ actual risk of breast cancer and absolute risk perceptions, comparative risk perceptions predicted anxiety and knowledge, but not intentions or behavior.
Comparative risk perceptions can affect patient outcomes like anxiety and knowledge independently of absolute risk perceptions and actual risk information.
comparative risk perception; breast cancer; behavioral decision-making; tamoxifen; decision aid
Although tamoxifen can prevent primary breast cancer, few women use it as a preventive measure. A second option, raloxifene, has recently been approved. The objective of the study was to determine women’s interest in tamoxifen and raloxifene after reading a decision aid describing the risks and benefits of each medication. Women with 5-year risk of breast cancer ≥1.66 from two large health maintenance organizations were randomized to receive a decision aid versus usual care. After reading an on-line decision aid that discussed the risks and benefits of tamoxifen and raloxifene, women completed measures of risk perception, decisional conflict, behavioral intentions and actual behavior related to tamoxifen and raloxifene. 3 months following the intervention, 8.1% of participants had looked for additional information about breast cancer prevention drugs and 1.8% had talked to their doctor about tamoxifen and/or raloxifene. The majority, 54.7%, had decided to not take either drug, 0.5% had started raloxifene, and none had started tamoxifen. Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs. Over 50% did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene. After reading a DA about tamoxifen and raloxifene, few women were interested in taking either breast cancer prevention drug.
decision aids; patient education; tamoxifen; raloxifene; breast cancer prevention
Tamoxifen reduces primary breast cancer incidence, yet has serious side effects. To date, few women with increased breast cancer risk have elected to use tamoxifen for chemoprevention. The objective of the study was to determine women’s knowledge of and attitudes toward tamoxifen following exposure to a tailored decision aid (DA).
632 women with a 5-year risk of breast cancer ≥1.66% (Mean=2.56, range=1.7-17.3) were recruited from 2 healthcare organizations. Participants viewed an online DA that informed them about their 5-year risk of breast cancer and presented individually-tailored content depicting the risks/benefits of tamoxifen prophylaxis. Outcome measures included behavioral intentions (to seek additional information about tamoxifen, to talk to a physician about tamoxifen, and to take tamoxifen); knowledge; and perceived risks and benefits of tamoxifen.
After viewing the DA, 29% of participants said they intended to seek more information or talk to their doctor about tamoxifen, and only 6% believed they would take tamoxifen. Knowledge was considerable, with 63% of women answering at least 5 of 6 knowledge questions correctly. Participants were concerned about the risks of tamoxifen and many believed that the benefits of tamoxifen did not outweigh the risks.
This study is the largest to date to test women’s preferences for taking tamoxifen and one of the largest to have tested the impact of a tailored decision aid. After viewing the DA, women demonstrated good understanding of tamoxifen’s risks and benefits, but most were not interested in taking tamoxifen for breast cancer chemoprevention.
decision aids; patient education; tamoxifen; breast cancer prevention
The identification of genetic variants associated with common disease is accelerating rapidly. “Multiplex tests” that give individuals feedback on large panels of genetic variants have proliferated. Availability of these test results may prompt consumers to use more healthcare services.
To examine whether offers of multiplex genetic testing increases healthcare utilization among healthy patients aged 25–40.
1,599 continuously insured adults aged 25–40 were surveyed and offered a multiplex genetic susceptibility test (MGST) for eight common health conditions.
Main Outcome Measure
Healthcare utilization from automated records was compared in 12 month pre- and post-test periods among persons who completed a baseline survey only (68.7%), those who visited a study Web site but opted not to test (17.8%), and those who chose the MGST (13.6%).
In the pre-test period, persons choosing genetic testing used an average of 1.02 physician visits per quarter compared to 0.93 and 0.82 for the other groups (p<0.05). There were no statistically significant differences by group in the pre-test use of any common medical tests or procedures associated with four common health conditions. When changes in physician and medical test/procedure use in the post-test period were compared among groups, no statistically significant differences were observed for any utilization category.
Persons offered and completing multiplex genetic susceptibility testing used more physician visits prior to testing, but testing was not associated with subsequent changes in use. This study supports that multiplex genetic testing offers can be provided directly to patients in such a way that use of health services are not inappropriately increased.
genetic susceptibility; delivery of health care; genetic testing; genetic counseling
To test the relationships between worry and perceptions of likelihood and severity (two indicators of risk perception) across eight common diseases, and to examine contributions of individual and disease variability in worry and risk perceptions.
Participants were 294 people recruited through the Multiplex Initiative, in which a genetic susceptibility test for 8 common diseases was offered to healthy adults. Participants completed a baseline telephone survey and Web-based surveys measuring the variables for this ancillary study, without a commitment to be tested.
Between- and within-subjects analyses yielded the following findings: 1) worry is more related to likelihood perceptions than to severity perceptions; 2) severity perceptions add significantly to explained worry variances above and beyond likelihood perceptions; 3) the likelihood × severity perception does not add to explained variance in worry above its components; 4) risk perceptions and worries form two identifiable clusters: cancer diseases and cardiovascular-metabolic diseases; 5) there are significant differences in risk perceptions and worry among diseases; 6) there are significant gender differences in risk perceptions and worry about common diseases; 7) variance in risk perception and worry is explained by a combination of between- and within-subjects variances, with the latter being more powerful.
Risk perception research should pay attention to severity perceptions, within-subjects variability and inter-disease differences should not be ignored, gender perspectives on illness perceptions should be acknowledged, and health psychologists must prepare for considering groups of illnesses in addition to single diseases.
risk perception; worry; severity; likelihood; within-subjects
Examination of patients’ responses to direct-to-consumer genetic susceptibility tests is needed to inform clinical practice. This study examined patients’ recall and interpretation of, and responses to, genetic susceptibility test results provided directly by mail.
This observational study had 3 prospective assessments (before testing; 10 days after receiving results; 3 months later). Participants were 199 patients aged 25–40 who received free genetic susceptibility testing for 8 common health conditions.
Over 80% correctly recalled their results for the 8 health conditions. Patients were unlikely to interpret genetic results as deterministic of health outcomes (mean=6.0, SD=0.8 on 1–7 scale, 1 indicating strongly deterministic). In multivariate analyses, patients with the least deterministic interpretations were White (p=.0098), more educated (p=.0093), and least confused by results (p=.001). Only 1% talked about their results with a provider.
Findings suggest that most patients will correctly recall their results and will not interpret genetics as the sole cause of diseases. The subset of those confused by results could benefit from consultation with a health care provider, which could emphasize that health habits currently are the best predictors of risk. Providers could leverage patients’ interest in genetic tests to encourage behavior changes to reduce disease risk.
Direct-to-consumer genetic tests; genetic testing; understanding; provider-patient communication; public health genomics
Increased availability of genetic risk information may lead the public to give precedence to genetic causation over behavioral/environmental factors, decreasing behavior change motivation. Few population-based data inform these concerns.
We assess the association of family history, behavioral risks, and causal attributions for diseases and the perceived value of pursuing information emphasizing health habits or genes.
1959 healthy adults completed a survey that assessed behavioral risk factors, family history, causal attributions of eight diseases, and health information preferences.
Participants’ causal beliefs favored health behaviors over genetics. Interest in behavioral information was higher than in genetic information. As behavioral risk factors increased, inclination toward genetic explanations increased; interest in how health habits affect disease risk decreased.
Those at greatest need for behavior change may hold attributions that diminish interest in behavior change information. Enhancing understanding of gene-environment influences could be explored to increase engagement with health information.
genetic testing; attribution; family history; behavioral risk factors
To evaluate what psychological and behavioral factors predict who is likely to seek SNP-based genetic test for multiple common health conditions where feedback can be used to motivate primary prevention.
Adults aged 25 to 40, who were enrolled in a large managed care organization were surveyed. Those eligible could log on to a secure study Web site to review information about the risks and benefits of a SNP-based genetic test and request free testing. Two primary outcomes are addressed: Accessing the Web (yes, no) and deciding to be tested (completed a blood draw at the clinic)
Those considering genetic susceptibility testing did hold genetically deterministic beliefs (0.42 on scale of 0-behavior to 1-genetic), but believed genetic information to be valuable and were confident they could understand such information. Individuals who believed it important to learn about genetics (OR=1.28), were confident they could understand genetics (OR=1.26), and reported the most health habits to change (OR=1.39) were most likely to get tested.
Physician-patient interactions could benefit if physicians develop “net friendly” strategies to capitalize on patients’ interest in online genetics information and leverage the interaction as a teachable moment to encourage family health history assessment and improved health behaviors.
personalized genomics; risk assessment; internet; psychosocial predictors
New genetic tests reveal risks for multiple conditions simultaneously, although little is understood about the psychological factors that affect testing uptake. We assessed a conceptual model called the Multiplex Genetic Testing Model (MGTM) using structural equation modeling (SEM). The MGTM delineates worry, perceived severity, perceived risk, response efficacy and attitudes toward testing as predictors of intentions and behavior. Participants were 270 healthy insured adults age 25–40 from the Multiplex Initiative conducted within a health care system in Detroit MI, USA. Participants were offered a genetic test that assessed risk for eight common health conditions. Confirmatory factor analysis revealed that worry, perceived risk and severity clustered into two disease domains: cancer or metabolic conditions. Only perceived severity of metabolic conditions was correlated with general response efficacy (β=0.13, p<0.05), which predicted general attitudes toward testing (β=0.24, p<0.01). Consistent with our hypothesized model, attitudes towards testing were the strongest predictors of intentions to undergo testing (β=0.49, p<0.01), which in turn predicted testing uptake (OR 17.7, β=0.97, p<0.01). The MGTM explained a striking 48% of the variance in intentions and 94% of the variation in uptake. These findings support use of the MGTM to explain psychological predictors of testing for multiple health conditions.
Genetic testing; Multiplex Initiative; health behavior; common disease; structural equation modeling; personalized medicine; U.S.A.
Identification of women with early stage breast cancer who will develop distant metastasis may improve clinical management. The transcriptional regulator Enhancer of Zeste-2 (EZH2) is over expressed in invasive breast carcinoma compared to benign breast tissues, with maximal expression in breast cancer metastasis. Our purpose was to investigate the performance of EZH2 protein detection as a predictor of metastasis in women with early stage breast cancer, which is unknown. We developed a cohort of 480 women with stage I-IIA breast cancer diagnosed between 1996 and 2002 and recorded detailed socio demographic, clinical and pathological information. Tumors were histologically characterized and arrayed in tissue microarrays containing 1,443 samples. Nuclear EZH2 expression was investigated by immunohistochemistry and was scored as 1–2 (negative and weak) or 3–4 (moderate and strong) using a validated scoring schema. Scores 1–2 were considered low EZH2; scores 3–4 were considered high EZH2. We found that after a median follow up of 9 years (range 0.04–14.5 years) 46 of 480 patients (9.6%) developed distant metastasis. High EZH2 was associated with larger size, high histological grade, negative hormone receptors, and first degree family history of breast and/or ovarian carcinoma. While EZH2 could not predict survival in the entire cohort, high EZH2 was a predictor of disease-specific survival in patients with early stage disease and first degree family history (log rank p-value 0.05). Importantly, in this group of patients, high EZH2 was an independent predictor of distant metastasis up to 15 years after primary carcinoma diagnosis (hazard ratio 6.58, 95% CI: 1.40–30.89, p=0.016) providing survival information above and beyond currently used prognosticators. In conclusion, EZH2 may bea useful biomarker of long-term metastatic risk in women with familial early stage breast cancer, and warrant further validation studies.
EZH2; Enhancer of Zeste-2; prognosis; recurrence; metastasis; breast cancer
Few data exist to inform concerns raised by online direct-to-consumer marketing of genetic susceptibility tests, such as those offered by commercial entities like 23andme, Navigenics, and DNA Direct. The Multiplex Initiative, a population-based study of healthy adults, provides the first opportunity to evaluate how use of a Web-based decision tool that conveyed information about a genetic susceptibility test influenced individuals’ test decisions.
To inform the ongoing debate over whether individuals offered genetic susceptibility testing without the involvement of a health care provider (eg, through direct-to-consumer testing) can make informed decisions about testing when guided by online decision aids.
Participants were 526 members of a large health maintenance organization aged 25 to 40 years old who visited a study website. Multivariate logistic regression models were tested to examine the association of website usage with downstream test decisions.
Participants viewed an average of 2.9 of the 4 pages introducing the multiplex test, 2.2 of the 8 pages describing the health conditions, and 3.2 of the 15 pages describing the genes. For each page viewed, participants were more likely to describe their decision-making as easy (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.07) and to decide to be tested (OR 1.08, 95% CI 1.05-1.11).
Healthy adults in this study perceived Web-based genomic information presented using evidence-based communications approaches to be helpful in supporting both decisions to test and not to test. Continued research is needed to ensure that these results generalize to target groups with lower literacy and less Internet savvy.
Genetic testing/methods; genetic testing/psychology; genetic predisposition to disease/psychology; health knowledge, attitudes, practice; health surveys; internet/utilization; polymorphism, single nucleotide; public health/methods; risk assessment/methods
Data from Arab world studies suggest that Arab women may experience a more aggressive breast cancer phenotype. To investigate this finding, we focused on one of the largest settlements of Arabs and Iraqi Christians (Chaldeans) in the US, metropolitan Detroit- a SEER reporting site since 1973.
Materials and Methods
We identified a cohort of primary breast cancer cases diagnosed 1973–2003. Using a validated name algorithm, women were identified as being of Arab/Chaldean descent if they had an Arab last or maiden name. We compared characteristics at diagnosis (age, grade, histology, SEER stage, and marker status) and overall survival between Arab-, European-, and African-Americans.
The cohort included 1,652 (2%) women of Arab descent, 13,855 (18%) African-American women, and 63,615 (80%) European-American. There were statistically significant differences between the racial groups for all characteristics at diagnosis. Survival analyses overall and for each SEER stage showed that Arab-American women had the best survival, followed by European-American women. African-American women had the poorest overall survival and were 1.37 (95% confidence interval: 1.23–1.52) times more likely to be diagnosed with an aggressive tumor (adjusting for age, grade, marker status, and year of diagnosis).
Overall, Arab-American women have a distribution of breast cancer histology similar to European-American women. In contrast, the stage, age, and hormone receptor status at diagnosis among Arab-Americans was more similar to African-American women. However, Arab-American women have a better overall survival than even European-American women.
Arab; breast cancer; epidemiology; incidence; survival