Racial Differences in the Use of BRCA1/2 Testing Among Women With a Family History of Breast or Ovarian Cancer FREE

Mutations in BRCA1 or BRCA2 confer a significantly increased risk of breast and ovarian cancer. Women with a BRCA1/2 mutation have a lifetime breast cancer risk of 50% to 85% and a lifetime ovarian cancer risk of 14% to 40%.¹ Testing for mutations in BRCA1/2 can provide individual information about breast and ovarian cancer risk that may affect decisions about prophylactic surgery, chemoprevention, and screening.² In addition, the identification of a BRCA1/2 mutation within a family can allow other family members to better define their own risk of cancer. BRCA1/2 mutations are rare in the general population; however, women with a family history of breast and ovarian cancer are at increased risk of carrying a mutation.³

Although clinical testing for BRCA1/2 mutations became available in 1996, relatively little is known about the determinants of testing use in the general population, including potential racial differences in utilization. Although many prior studies have examined interest in testing among the general population, the correlation between level of interest and actual testing use has been poor and the determinants of interest inconsistent.^4- 8 Most prior studies of actual use of testing have focused on (1) decisions about testing once women have participated in genetic counseling; (2) descriptive characteristics of women undergoing testing; or (3) the uptake of testing among high-risk families involved in research protocols.^9- 14 These studies have generally included mostly white women. However, it is unclear whether this low prevalence of nonwhite participants represents the populations being studied (eg, hereditary breast cancer families participating in research registries) or indicates a racial disparity in the use of testing.

There are several reasons to believe that racial disparities in the use of predictive genetic testing are likely to exist. Disparities have been demonstrated in most areas of health care and may be greatest for new technologies.¹⁵ Some populations may be particularly likely to distrust genetic testing because of historical attempts to label certain racial groups as genetically inferior.¹⁶ Genetic testing is expensive and may be inaccessible to individuals with fewer financial resources. Racial differences in attitudes have been demonstrated for many components of medical care and may exist for genetic testing.¹⁷

Given the lack of empirical data about the utilization of genetic testing in the general population and concern about the potential existence of racial disparities in this area, the goals of this study were to assess the association between race and use of genetic counseling for BRCA1/2 testing among women at risk of carrying a BRCA1/2 mutation and to evaluate the potential contributions of socioeconomic characteristics, cancer risk perception and worry, attitudes about genetic testing, and interactions with primary care physicians to this association.

We conducted a health system population–based case-control study to identify the determinants of the use of genetic counseling for BRCA1/2 testing among women with a family history of breast or ovarian cancer. The use of BRCA1/2 counseling was selected as the outcome of interest because we were interested in the factors associated with referral for genetic testing rather than the decisions about testing after genetic counseling. Approximately three quarters of women who underwent counseling completed BRCA1/2 testing after counseling. The study protocol was approved by the institutional review board at the University of Pennsylvania.

The reference population was defined as women between the ages of 18 and 80 years who had seen a primary care physician within the University of Pennsylvania Health System in the 3 years prior to the start of the study. During the study, the University of Pennsylvania Health System included approximately 225 primary care physicians who saw more than 250 000 primary care patients annually. The primary care physician population was 42% women; 5.4% African American, 7.7% Asian American, 1.5% Hispanic, and 85.4% white. The reference population was identified using billing databases. Women from the reference population were included in the study if they had a first- or second-degree relative with a breast or ovarian cancer diagnosis. Because the primary aim of the study was to identify the determinants of BRCA1/2 counseling among women who would be targeted for primary cancer prevention, women were excluded if they had a personal diagnosis of breast or ovarian cancer. In addition, women were excluded if they were identified as being unable to participate because of illness or mental incapacity by their primary care physician.

Cases were all women from the reference population who presented for genetic counseling at the Cancer Risk Evaluation Program at the University of Pennsylvania Health System between December 1999 and August 2003. At the time of the study, the Cancer Risk Evaluation Program was the primary provider practice of genetic counseling within the University of Pennsylvania Health System. Of the 449 women who participated in the Cancer Risk Evaluation Program over the study period, 355 completed data collection for a response rate of 79%.

Controls were a random sample of women from the reference population who had not participated in genetic counseling for BRCA1/2 testing. Controls were accrued every 6 months during the study to approximate the timing of case accrual. At each 6-month interval, a sample of controls was selected equal to twice the number of cases accrued over the prior 6 months. Controls were excluded if they had previously participated in BRCA1/2 genetic counseling. Of the 956 eligible controls, 603 were successfully enrolled for a response rate of 63.1%.

It was not possible to assess personal or family cancer history from the billing database. Thus, family and personal history of cancer was measured by self-report at the time of data collection and used to define the final study population. Of the 1062 women who completed data collection, 392 women were not included in the final sample because they did not have a family history of breast cancer (375 controls and 17 cases). In addition, 254 women were excluded because they had a personal diagnosis of breast cancer (38 controls and 224 cases).

Data were collected using a mailed self-administered questionnaire, with cases completing the questionnaire prior to being seen at the Cancer Risk Evaluation Program. Potential participants were informed that participation was completely voluntary and would have no effect on their medical care, that their responses would be confidential, and that completion of the questionnaire represented their consent to participate.

Sociodemographic Characteristics. Age, education, and annual household income were measured using items from the Behavioral Risk Factor Surveillance System 1998 questionnaire.¹⁸ Race/ethnicity and religious heritage were measured by self-report using items developed from the US Census guidelines.¹⁹

Probability ofBRCA1/2Mutation. Each woman’s probability of carrying a BRCA1/2 mutation was calculated from a prediction model developed by Frank et al.^20- 21 This model includes family history of breast cancer (number of relatives diagnosed before age 50 years and number of relatives diagnosed at age 50 years or older), family history of ovarian cancer, and Ashkenazi Jewish heritage.

Cancer Risk Perception and Worry. Participants were asked to rate their lifetime risk of developing cancer in 3 ways: (1) on a scale from 0% to 100%; (2) on a 7-point Likert scale ranging from very low to very high; and (3) compared with the average woman using a 7-point Likert scale ranging from much lower to much higher.²² Risk perception was assessed separately for breast and ovarian cancer. Because items for each cancer were highly correlated and the results were substantively the same irrespective of the measure used, we present the analyses using the comparative 7-point Likert scale for each cancer. Cancer worry was measured using a previously developed scale that includes 2 items: “How often do you worry about developing breast (or ovarian) cancer?” and “How often does worry about breast (or ovarian) cancer interfere with your life?” with response options on a 7-point Likert scale ranging from not at all to all of the time.²³ Separate breast and ovarian cancer worry scores were created by averaging the scores for the 2 items for each cancer.

Attitudes About Genetic Testing. Attitudes were assessed by asking participants to endorse statements about the risk and benefits of BRCA1/2 testing using a 7-point Likert scale ranging from strongly disagree to strongly agree.^9,24 For these analyses, attitudes were grouped into 4 domains: information from testing (6 items); discrimination from testing (3 items); reassurance from testing (2 items); and anxiety from testing (2 items). Summative scores were created for each of these domains by averaging the scores on individual items. The multi-item measures of information from testing and discrimination from testing had reasonable internal consistency (Cronbach α, 0.74 and 0.77, respectively) and item total correlations between 0.34 and 0.76.

Primary Care Physician Visits and Discussions ofBRCA1/2Testing. Individual items assessed how often the respondent had seen a gynecologist and how often she had seen a primary care physician other than a gynecologist in the past year. Response options were 0 times, 1 to 2 times, 3 to 5 times, and more than 5 times. In addition, for each specialty of physician, respondents were asked if they had discussed BRCA1/2 testing.

Fisher exact tests, χ² tests, and t tests were used to assess the statistical significance of differences in the characteristics of cases and controls as indicated. Because the risk perception, cancer worry and attitudinal measures were ordinal variables and not normally distributed, we categorized scores into 3 groups based on a priori cut points: low (scores<4); medium (score of 4); and high (scores>4). These measures were compared between cases and controls using χ² tests. Multiple logistic regression was used to adjust the association between race and use of BRCA1/2 counseling for potential mediating and confounding variables, which we specified a priori. Because less than 10% of our study population was from racial/ethnic groups other than African American and white, we focused the multivariate analyses on the comparison of African American and white women and excluded women of other racial/ethnic groups from the analyses. Groups of variables were added sequentially to the model to observe the effect on the race coefficient. Age, probability of a BRCA1/2 mutation, risk perception, cancer worry, and attitudinal variables were entered into the model as linear terms. Because some of the psychological factors (risk perception and worry) were moderately correlated (Pearson correlation coefficients, 0.19-0.58) and potentially introduced collinearity into the model, we also constructed models using a composite score for risk perception/cancer worry. The race coefficient in the model using the composite score was not substantively different from the model including each individual measure of risk perception and worry; thus, we present the models with the individual measures. The final model demonstrated reasonable performance with a nonsignificant Hosmer-Lemeshow goodness-of-fit statistic (P = .34; 10 groups) and a C statistic of 0.92. The analyses were conducted using Stata 7.0 software package (Stata Corp. College Station, Tex). All hypothesis tests were 2-tailed, using a P = .05 level of significance.

The characteristics of the 217 cases and 191 controls are reported in TABLE 1. Among women with a family history of breast or ovarian cancer, women who underwent BRCA1/2 counseling (cases) were significantly less likely to be African American than women who did not undergo BRCA1/2 counseling (7.4% of cases vs 28.8% of controls). In addition, women undergoing BRCA1/2 counseling had a greater probability of carrying a BRCA1/2 mutation, were younger, more likely to be Jewish, and more likely to be married. Education and annual household income levels were associated with use of BRCA1/2 counseling but type of health insurance coverage was not. Women who underwent BRCA1/2 counseling were more likely to have seen a gynecologist more than 2 times in the past year, but less likely to have seen a primary care physician other than a gynecologist. Discussion of BRCA1/2 testing by their gynecologist or primary care physician was associated with use of BRCA1/2 counseling.

Cancer risk perception, cancer worry, and attitudes about BRCA1/2 testing are reported in (TABLE 2). Each measure of risk perception and worry was significantly higher among cases than controls. Attitudes about genetic testing were also significantly associated with the use of BRCA1/2 counseling, with women who underwent counseling being more likely to endorse the benefits of testing including the potential to gain information and reassurance. Interestingly, women who underwent BRCA1/2 counseling were more likely to endorse concerns about anxiety from BRCA1/2 testing.

The estimate of the inverse association between African American race and BRCA1/2 counseling changed very little after adjustment for probability of a BRCA1/2 mutation, socioeconomic characteristics, cancer risk perception and worry, attitudes about genetic testing, and primary care physician visits and discussions of BRCA1/2 testing (TABLE 3). Adjustment for racial differences in BRCA1/2 mutation probability, sociodemographic factors, and risk perception led to slight increases in the point estimate of the odds ratio (OR) for the association between race and BRCA1/2 counseling (OR, 0.22-0.40), with the race coefficient no longer reaching strict statistical significance in the model including probability of a BRCA1/2 mutation, sociodemographic factors, and psychological factors (OR, 0.40; P = .08). However, further adjustment for attitudes about genetic testing and primary care physician interactions yielded a decrease in the point estimate for the race coefficient (OR, 0.40-0.28) and increase in the statistical significance. In the final multivariate analysis, use of BRCA1/2 counseling remained strongly inversely associated with African American race (P = .01). This association also held when the sample was restricted to women who were not of Ashkenazi descent (adjusted OR, 0.26; 95% confidence interval [CI], 0.07-0.94). In addition, in the final model, use of BRCA1/2 counseling was positively associated with the probability of BRCA1/2 mutation, younger age, higher breast cancer risk perception, higher ovarian cancer worry, and attitudes about discrimination and reassurance from testing. In addition, use of BRCA1/2 counseling was more common among women who had discussed BRCA1/2 testing with their gy necologist or other primary care physician.

This study demonstrates that African American women with a family history of breast or ovarian cancer are much less likely to undergo genetic counseling for BRCA1/2 testing than are white women with a family history of breast or ovarian cancer. Furthermore, this racial disparity is not explained by differences in the probability of carrying a BRCA1/2 mutation, socioeconomic status, cancer risk perception and worry, attitudes about BRCA1/2 testing, or primary care physician discussions of BRCA1/2 testing.

Racial disparities in the clinical use of genetic susceptibility testing have been widely anticipated but, to our knowledge, this is the first prospective study to document their occurrence. Prior studies have demonstrated racial differences in attitudes about genetic testing, as well as racial differences in cancer risk perception and response to education and counseling about BRCA1/2 testing in a research setting.^24- 27 We previously noted a racial difference in the early uptake of BRCA1/2 testing; however, that study was limited by its retrospective design, small sample size, and inability to examine potential causes of racial differences in use of BRCA1/2 counseling.²⁸ In addition to providing some of the first empirical evidence of a racial disparity in utilization of genetic testing in clinical practice, the results of this study are important because of the magnitude of the disparity, with white women having almost 5 times the odds of undergoing BRCA1/2 counseling as African American women.

Because the benefit of BRCA1/2 testing for all women with a family history of breast or ovarian cancer is controversial, the implications of racial disparities in the use of BRCA1/2 testing are complex. On one hand, BRCA1/2 testing provides information about breast and ovarian cancer risk that can influence decisions about cancer risk reduction and save lives. For example, prophylactic oophorectomy has been demonstrated to reduce the risk of ovarian cancer by more than 90%, extend life expectancy by more than 3 years, and be widely acceptable to women with BRCA1/2 mutations who have completed childbearing.^2,29- 30 On the other hand, the risk information provided by BRCA1/2 testing is imprecise, testing is expensive, and BRCA1/2 mutations are relatively rare, even among women with a family history of breast or ovarian cancer. Furthermore, many of the available breast cancer risk-reduction interventions involve significant trade-offs and uptake of interventions such as prophylactic mastectomy or tamoxifen chemoprevention among mutation carriers is far from universal.^29- 30 Given these issues, not all women with a family history of breast or ovarian cancer will choose to undergo counseling for BRCA1/2 testing. However, although the optimal proportion of women with a family history of breast or ovarian cancer who should undergo counseling for BRCA1/2 testing remains uncertain, there are no clear clinical reasons why utilization should differ between African American and white women with a family history of breast or ovarian cancer. Breast cancer incidence is lower among African American than white women in the United States, but breast cancer is diagnosed younger and case fatality is higher among African American women, resulting in similar benefits from prevention and early detection.³¹ Although the published data are sparse, several studies have suggested that the prevalence of mutations in African American hereditary breast cancer families may be similar to that in white hereditary breast cancer families.^32- 36 In our sample of women with a first- or second-degree relative with breast or ovarian cancer, the predicted probability of a BRCA1/2 mutation differed very little between African American and white women. Thus, racial differences in utilization of BRCA1/2 counseling cannot be directly attributed to differences in the clinical utility of BRCA1/2 testing.

The racial disparity in use of BRCA1/2 counseling in this population was not explained by differences in the probability of carrying a BRCA1/2 mutation, socioeconomic status, cancer risk perception and worry, attitudes about the risks and benefits of BRCA1/2 testing, or primary care physician discussions of BRCA1/2 testing. In fact, in contrast to many other clinical scenarios, the strength of the association between race and use of BRCA1/2 counseling changed very little after multivariate adjustment. Other factors must contribute to this disparity. Health care related–distrust has been demonstrated to be higher among African Americans than whites and may serve as a barrier to use of medical care.^37- 38 New technologies, such as genetic testing, may be particularly sensitive to the effects of distrust. We are currently exploring the role of health care distrust in this and other areas where racial disparities have been demonstrated in cancer control. Some groups may be reluctant to undergo genetic testing because of concerns about how genetic information may be used. We have recently demonstrated that African Americans are more likely to be concerned about racial discrimination on the basis of genetic testing.²⁴ Although African American women were no more likely to report concern about insurance or employment discrimination on the basis of BRCA1/2 testing, the specific concern about racial discrimination was not measured in the current study and may contribute to the disparity in uptake. Alternatively, racial differences in use of BRCA1/2 counseling may reflect differences in the characteristics of the primary care physicians of African American and white women rather than differences in the characteristics of the women themselves. If women of different races see different types of primary care physicians who are associated with different probabilities of referral for BRCA1/2 counseling, the racial difference in use of BRCA1/2 counseling could arise from the clustering of African American patients with certain types of physicians. Such types might be defined by characteristics that are often used to describe physicians, such as specialty, practice setting, and demographics, or by behavioral or attitudinal characteristics that may be more predictive of making referrals for BRCA1/2 counseling, such as the tendency to be an early or late adopter of new technology.³⁹ This possibility is supported by recent evidence that African Americans are seen by a relatively small proportion of primary care physicians across the United States and that primary care physicians seen by African Americans are less likely to be board certified and more likely to report difficulty delivering high quality care than primary care physicians for visits by whites.⁴⁰ Because the current study was designed to examine the contribution of patient level characteristics to a potential racial difference in use of BRCA1/2 counseling, we were unable to assess the contribution of differences in physician characteristics. However, given the lack of explanatory power of patient characteristics, differences in physician characteristics should be an important focus of future research.³⁹

This study also informs the broader research agenda in racial disparities in health care. Unlike many prior studies investigating the causes of racial disparities, we were able to test the contribution of a broad range of potential causes including clinical, socioeconomic, psychological, attitudinal, and primary care factors. The results of these analyses highlight several issues. First, although residual racial differences in medical care after adjustment for clinical and socioeconomic factors are often attributed to racial differences in attitudes or perceptions of risk, in this study, adjusting for racial differences in attitudes and risk perception only increased the size of the racial disparity in utilization.¹⁵ Second, the large racial difference in the use of BRCA1/2 counseling was not explained by the factors that are traditionally cited as the predominant causes of racial disparities in health care.¹⁵ Third, the size of the disparity in utilization of BRCA1/2 counseling is larger than those seen with more established technologies such as cardiac catheterization.¹⁵ Together, these issues emphasize the growing recognition that all racial disparities are not alike and the causes of racial disparities are likely to vary substantially across clinical setting, time, and place.

This study provides insight into other factors that are associated with utilization of clinical BRCA1/2 counseling among women with a family history of breast or ovarian cancer in the general population. Several of these factors are not surprising. BRCA1/2 counseling is more common among women who are at increased risk of carrying a mutation and who have a higher perceived risk of breast cancer. Younger age and having had a primary care physician or gynecologist discuss BRCA1/2 testing are also associated with use of BRCA1/2 counseling, as well as the belief that BRCA1/2 testing will provide reassurance and the absence of concern about discrimination from BRCA1/2 testing. Perhaps somewhat more surprisingly, concern about anxiety from BRCA1/2 testing was higher among women seeking BRCA1/2 counseling than controls, suggesting that this concern is not a significant barrier to the use of genetic testing. This association is supported by a prior study that demonstrated higher cancer distress among women choosing to undergo testing.¹²

The results of this study must be considered within its limitations. We studied women within a large health system in the greater Philadelphia area and our results may not generalize to women who do not see a primary care physician or who live in other areas of the United States or elsewhere. In addition, we were unable to examine use of BRCA1/2 counseling among other racial or ethnic groups because these groups are not well represented in our health system population. It is possible that some women who receive primary care through our health care system may have undergone BRCA1/2 counseling outside of the health care system during the study period. To assess this possibility, we surveyed health care system primary care physicians at the study mid point about the use of BRCA1/2 counseling among their patients. None reported having a patient who had undergone counseling at a different site. Thus, we believe our case ascertainment to be reasonably complete.

Our response rate was lower among controls than cases and raises concerns about possible response bias. To assess this possibility, we compared responders and nonresponders on age and race/ethnicity, the 2 variables available from the billing database. Among the cases, responders did not differ significantly from nonresponders in age or race/ethnicity. Among the controls, responders did not differ from nonresponders in age but were slightly less likely to be African American than were nonresponders (33% vs 38%; P = .02), suggesting that our assessment of the magnitude of the racial disparity in use of BRCA1/2 testing is conservative. We did not collect information about unaffected relatives and were unable to calculate BRCA1/2 probabilities using models that include such information.⁴¹ However, the predictive model we used is widely accepted for use in genetic counseling and represented the standard of care for the majority of the study period.³ As noted previously, uncertainty remains about who should undergo BRCA1/2 testing and the limited data about mutation prevalence among some groups of women who are not white may increase the uncertainty about testing in this population. However, paradoxically, the pronounced racial disparity in use of genetic testing contributes to this lack of data about mutation prevalence, creating the potential for a vicious cycle of lack of information and lower rates of utilization of a potentially beneficial technology.

The complex and highly charged relationship between race and genetics presents a substantial challenge to the translation of advances in human genetics into improvements in health. Although empirical evidence of racial disparities in the utilization of BRCA1/2 counseling provides important information about this challenge, it only further highlights the need to move forward in developing health and social policy that ensures the potential benefits of the Human Genome Project are realized for all segments of the US population.