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Increased Uptake of BRCA1/2 Genetic Testing Among African American Women With a Recent Diagnosis of Breast Cancer

Lisa R. Susswein, Cécile Skrzynia, Leslie A. Lange, Jessica K. Booker, Mark L. Graham, III, James P. Evans

From the Department of Genetics, Department of Pathology, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill; and Waverly Hematology Oncology, Cary, NC

Corresponding author: James P. Evans, MD, PhD, University of North Carolina at Chapel Hill, Department of Genetics, CB#7264, Chapel Hill, NC 27599-7264; e-mail: jpevans{at}med.unc.edu

	ABSTRACT

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Purpose: Studies suggest that African American women are less likely to pursue BRCA1/2 genetic testing than white women. However, such studies are often confounded by unequal access to care.

Methods: Data from 132 African American and 636 white women, obtained from a clinical database at the University of North Carolina (Chapel Hill, NC) between 1998 and 2005, were analyzed to assess BRCA1/2 genetic testing uptake. Importantly, the clinical setting minimized barriers of both cost and access. Race and time of new breast cancer diagnosis (recent v > 1 year before genetic evaluation) were assessed for association with BRCA1/2 testing uptake using multivariable logistic regression models.

Results: Both race (P = .0082) and a recent diagnosis of breast cancer (P = .014) were independently associated with testing uptake. African American women had a lower estimated odds of pursuing testing than white women (odds ratio [OR], 0.54; 95%CI, 0.34 to 0.85), and women with a recent diagnosis had a higher OR than those with a remote diagnosis (OR, 1.58; 95% CI, 1.10 to 2.29). In a race-stratified analysis, there was no statistical evidence for association between recent status and testing uptake in the larger white stratum (OR, 1.38, P = .13) while there was for the smaller African American sample (OR, 2.77, P = .018). The test of interaction between race and remote status was not significant (P = .15).

Conclusion: African American race was associated with an overall decreased uptake of BRCA1/2 genetic testing, even when barriers of ascertainment and cost were minimized. However, among African American women, a recent diagnosis of breast cancer was associated with substantially increased uptake of testing.

	INTRODUCTION

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A woman who harbors a deleterious mutation in the BRCA1 or BRCA2 gene has a substantially elevated lifetime risk of developing breast and ovarian cancer. Since their discovery in 1994 and 1995, there has been a steep increase in clinical mutational analysis of these genes. BRCA1/2 genetic testing is offered to individuals considered to be at increased risk to carry a mutation and allows the opportunity to guide medical management through prophylactic surgery, pharmacologic intervention, and increased surveillance.^1-3

As the utilization of genetic testing has increased, the clinical settings in which it is pursued have expanded. Traditionally, BRCA1/2 testing has been discussed with patients in a nonacute medical setting. These women typically have either a remote personal history of breast or ovarian cancer or a concerning family history. In this traditional setting, decisions related to genetic testing are rarely time-sensitive, and there are typically few competing medical issues at the time of counseling. However, in recent years, BRCA1/2 genetic testing has also become a consideration for women at the time of a breast or ovarian cancer diagnosis.⁴ Knowledge of their mutational status can inform women's medical management decisions in the acute setting, specifically regarding whether to pursue risk-reducing bilateral mastectomy at the time of treatment for newly diagnosed breast cancer.^5,6

As is the case with many aspects of medical care, racial disparities exist in clinical genetics.⁷ Studies have demonstrated a lower use of genetic services among African American compared with white patients, particularly with respect to BRCA1/2 genetic testing.^8,9 Researchers have hypothesized that this decreased utilization of genetic testing among African Americans is related to the potential risk of discrimination,^10,11 less knowledge about breast cancer genetics,¹² or cultural and familial differences.¹³ Finally, at $3,120 (US$), BRCA1/2 testing is one of the most expensive blood tests in current medical practice; the high cost of testing is a deterrent for many patients.¹⁴

The University of North Carolina (UNC; Chapel Hill, NC) Cancer Genetics Clinic, which serves a racially and economically diverse patient population, is in a unique position to study the uptake of BRCA1/2 testing without confounding issues of ascertainment bias or cost—two major obstacles to genetic services. In our clinic, every newly diagnosed patient with breast cancer who has potential genetic issues is approached by the genetics team regardless of race, socioeconomic status, or the need for a formal referral. Through an agreement between Myriad Genetics Inc (Salt Lake City, UT) and our own hospital, we are able to provide BRCA1/2 genetic testing at no charge to patients who cannot afford commercial testing.

Within this context of minimized bias, we have quantified the uptake of BRCA1/2 genetic testing among patients seen by the UNC Cancer Genetics Service. In addition, we examined race and the timing of breast cancer diagnosis for association with testing uptake. Few studies have quantitatively examined the relatively new practice of offering BRCA1/2 testing to women with a recent breast cancer diagnosis, and none to our knowledge has further parsed this group of newly diagnosed women by race.

	METHODS

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The cancer genetics service at UNC maintains a confidential database that includes each patient's demographics, personal and family cancer history, risk of carrying a BRCA1/2 mutation, and genetic testing decisions. Risk of carrying a BRCA1/2 mutation was determined by utilizing relevant medical literature^15,16 and the BRCAPro¹⁷ computer model. The UNC Biomedical institutional review board granted permission to retrospectively query these clinical data in an anonymized fashion.

Between January 1998 and March 2007, the UNC genetics team provided genetic counseling to more than 3,000 individuals regarding inherited cancer risk. The current data set is a subset of our patients—women who had been diagnosed with breast cancer and who were counseled regarding BRCA1/2 risk. We focused these analyses on white and African American patients only, as other racial groups were not of sufficient sample size. Information regarding patients' race was gathered by self-report or from the medical record.

The data set was further restricted to include only those patients to whom genetic testing was offered, excluding patients who were not considered to be candidates for genetic testing. Those not offered testing were either at low enough risk such that genetic testing would not have been appropriate, had already undergone genetic testing, had a family member who was a better candidate for genetic testing, or were family members of previous patients who tested negative.

Patients were categorized as having a "recent" or "remote" diagnosis of breast cancer compared to when they were being seen for genetic counseling. We defined "recently diagnosed" patients as those who were the same age at consultation as at diagnosis. Those "remotely" diagnosed were at least 1 year older at consultation than they were at diagnosis and were either referred by a provider or were self-referred. Those patients in the "recently diagnosed" group were identified as part of the UNC multidisciplinary breast cancer clinic. In this setting, clinical information from all patients diagnosed with breast cancer each week are reviewed for appropriateness of genetic evaluation in the context of their comprehensive care, thus, minimizing referral bias. The final data set was composed of 768 women with complete data for the variables of interest.

We used Pearson's ² test to first test whether racial proportions within this sample were consistent with those from the general breast cancer population at our institution, as reflected in the UNC Tumor Registry. The Wilcox rank sum test was used to test for differences between African American and white patients in median age and estimated risk for carrying a BRCA1/2 mutation, because the distribution of these variables was characterized by considerable departure from normality.

We used multivariable logistic regression models to obtain estimated odds ratios (ORs) and corresponding 95% CIs for recent versus remote diagnosis and for African American versus white. Logistic regression models were adjusted by age at initial clinic visit and estimated risk of carrying a BRCA1/2 mutation. Finally, we also conducted race- and remote status–stratified analyses and performed a test of race x remote status interaction in the combined sample.

	RESULTS

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Between 1998 and 2007, the UNC genetics team offered BRCA genetic testing to 768 women with a diagnosis of breast cancer who were either African American (n = 132, 17%) or white (n = 636, 83%).

Of the 768 patients, 404 (53%) had been diagnosed at the same age as they were at consultation and were coded as having a "recent" diagnosis. The remaining 364 (47%) were coded as "remote," meaning that they were at least 1 year older at consultation than at diagnosis. As expected, patients with a recent diagnosis were younger at the time of genetic counseling than those who were diagnosed in the more remote past. These results were significant for both African American (median, 39.7 v 43.8 years; P = .002) and white patients (45.7 v 49.8; P < .001). There was no statistically significant difference between African American and white patients with respect to their median a priori risk of harboring a BRCA1/2 mutation (median, 0.14 and 0.14, respectively; P = .84).

Table 1 displays the racial proportions within our sample and from the UNC Tumor Registry. While the proportion of African American patients in our remotely diagnosed group differed significantly from that of the general population of breast cancer patients (14% v 21%; P = .009), there was no statistically significant difference between the proportion of African American patients in the recently diagnosed group and the general breast cancer patients (18% v 21%; P = .12).

	DISCUSSION

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Genetic testing of BRCA1/2 has become part of the routine care of women in an expanding array of clinical situations. Indeed, Myriad Genetics Inc has performed more than 100,000 mutational analyses of these genes since they began commercial testing, making BRCA1/2 perhaps the most sequenced genes in the history of medicine. Within this rapidly changing and often confusing environment,¹⁸ it is not surprising that African American and white patients hold varying attitudes about genetic testing. These different attitudes could have significant impact on medical care as genetic testing is increasingly used to guide decisions about medical management.

In this study, we evaluated the uptake of BRCA1/2 testing in a large group of white and African American patients. In addition, we investigated a rapidly emerging aspect of BRCA1/2 testing—the use of mutational analysis to guide decisions in the context of a recent diagnosis of cancer.

We found that, overall, African American women were less likely than white women to pursue genetic testing when offered, even when barriers of ascertainment and cost were absent. We also observed that among African American women, a recent (compared with remote) diagnosis of breast cancer is associated with a substantial rise in uptake of testing. Among white women, a recent diagnosis resulted in a modest estimated increased uptake of testing as well, though this increase did not reach a level of statistical significance. Given the nonsignificant test of interaction between race and recent versus remote diagnosis, we cannot statistically rule out that the increase in uptake is the same for African American and white women.

These observations demonstrate that when investigating racial disparities in medicine, context is vital; the same barriers to genetic testing that seem to exist in the traditional genetics clinic may not exist to the same extent for African Americans in the context of a recent diagnosis of breast cancer.

Most genetics clinics are heavily dependent on referrals. Given the hurdles that exist in our medical system to accessing secondary and tertiary care, ascertainment bias is likely to be a significant issue in the assessment of the African American experience in genetics clinics. Armstrong et al⁸ found that African Americans were significantly less likely than whites with comparable cancer family histories to have been referred for genetic counseling (OR, 0.22). In contrast, the records of all newly diagnosed patients at UNC are evaluated by the genetics team, eliminating the issue of referral bias within this group in particular.

The high cost of BRCA1/2 sequencing has proven to be a barrier to uptake of testing,¹⁴ and the effect would only be magnified for women in lower socioeconomic groups. In the current study, in addition to eliminating referral bias among our newly diagnosed population, we were also able to remove the barrier of cost. However, African American women were still overall less likely to pursue BRCA1/2 genetic testing than white women.

Numerous explanations have been put forth to account for the disparity between African American versus white interest in genetic testing (reviewed by Halbert et al¹³). Potential explanations for lower utilization of genetics services among African Americans include concern about potential abuse of genetic information, as documented by Peters et al,¹¹ as well as less knowledge about breast cancer genetics.^8,12

Differences in attitudes about family and community might also contribute to racial differences in medical decision-making.¹⁹ Baldwin et al²⁰ demonstrated that low-income African American women are highly influenced by their relationships with community and family when making decisions about medical care. Thompson et al¹² observed that African American women were more likely to refuse testing if they anticipated feeling guilty about their relatives' potential for harboring a mutation.

The factors discussed here may explain the overall disparity between African American and white individuals in their uptake of genetic testing, but cannot explain why in the midst of a new breast cancer diagnosis, African American women in our clinic demonstrated an increased uptake of testing by a factor approaching three.

Perhaps the immediacy of a breast cancer diagnosis has multiple effects that may increase the perceived value of genetic testing to a patient. First, the large impact of mutational status on immediate medical treatment could be a factor that prompts African Americans to pursue testing despite otherwise powerful cultural barriers. While it is true that our definition of "recently" diagnosed women includes some women who may be up to 1 year out from their breast cancer diagnosis and would therefore have already made their medical and surgical decisions, the group will also include many newly diagnosed women.

Second, the stress related to a recent cancer diagnosis may affect decision making. Cancer-related anxiety has been cited as a motivator for utilization of genetic services⁸; one study showed that, among 95 members of an African American family in which there was a BRCA1 mutation, those who expressed an interest in testing demonstrated higher levels of cancer-related stress.¹⁴ Thus, women might be more likely to pursue preventative therapies during this acute period than they would later, when the emotional trauma of a diagnosis of cancer may have faded.

Third, younger women may be more apt to embrace the new technology of genetic testing.¹⁴ African American women who were seen at the time of their diagnosis were significantly younger, as one would expect, than those who had been diagnosed in the remote past (median age, 37.5 v 44.0 years; P = .002). However, we performed model adjustment for age, which should, to some extent, have addressed this.

Finally, in the context of a multidisciplinary setting, genetic evaluation may be seen as part of one's overall care and on par with oncology, surgery, and radiation. In other words, the structure of multidisciplinary care as rendered in our clinic may remove the aura of "exceptionalism"²¹ often associated with genetics, and might encourage women to embrace testing.

The foregoing discussion seeks to explain why African American women who were recently diagnosed with breast cancer were more likely to undergo genetic testing than those with a remote diagnosis. On the other hand, the modest increase in uptake observed in white women did not reach statistical significance. Although recently diagnosed white women face many of the same stressors as African American women and stand to benefit similarly from genetic testing, perhaps the added stimulus of a recent diagnosis may not increase the interest of white women in testing from an already high level.

The current study has several limitations. We relied on self-identified race and did not include individuals who self identified as "other" or mixed race. In addition, our categorization of "recent" and "remote" were dependent on the timing of each patient's date of birth with respect to the date of diagnosis and counseling. There was likely some misclassification, but it would be in both directions. Moreover, the potential miscategorization of a subset of women in the study would tend to bias the results toward the null hypothesis of no association. The fact that we see significant differences between the recent and remote groups despite some inevitable misclassification only strengthens our conclusions.

Our data set did not include information about tumor staging or treatment decisions. It has been observed that both tumor characteristics and prognosis differ among races²²; such differences could account for the disparate levels of uptake of genetic testing. Future studies would ideally be able to adjust for stage of breast tumor and other treatment decisions. Finally, differences necessarily existed in the way in which patients from the "remotely" and "recently" diagnosed groups were referred for genetics evaluation. Remotely diagnosed patients were generally self-referred or referred by providers in a variety of specialties, while those patients in the recently diagnosed group were identified as part of the UNC multidisciplinary breast cancer clinic, in which all breast cancer patients are reviewed for appropriateness of genetic evaluation in the context of their comprehensive care, thus minimizing referral bias. However, comparisons were ultimately based on the assessment of uptake among patients who were actually offered testing by the genetics team and who therefore had comparable risks of harboring a mutation. Thus, differences in uptake are likely to indicate inherent differences in attitude between the two populations of patients.

It is important to note that almost half of all patients in the current study, and a greater proportion of African Americans than whites, had insufficient insurance coverage for testing. Were it not for the unique structure of our clinic and an ability to offer free testing, the high cost of BRCA1/2 analysis would have precluded these women from learning of their mutational status. Given the increasing utility of BRCA1/2 testing in clinical medicine, mechanisms for ensuring access to this sometimes prohibitively expensive test should be explored.

In conclusion, for patients diagnosed in the remote past, this study shows that African Americans were less likely than whites to pursue BRCA1/2 genetic testing, even when barriers of cost and access were minimized. However, in the setting of a recent diagnosis of breast cancer, racial differences may be attenuated. Elucidation of why a recent diagnosis of breast cancer increases African Americans' uptake of BRCA1/2 genetic testing so dramatically could contribute to a better understanding of racial disparities in genetic testing and medicine.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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The author(s) indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

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Conception and design: Lisa R. Susswein, Mark L. Graham III, James P. Evans

Financial support: James P. Evans

Provision of study materials or patients: Cécile Skrzynia, Mark L. Graham III, James P. Evans

Collection and assembly of data: Lisa R. Susswein, Jessica K. Booker, James P. Evans

Data analysis and interpretation: Lisa R. Susswein, Leslie A. Lange, Jessica K. Booker, Mark L. Graham III, James P. Evans

Manuscript writing: Lisa R. Susswein, James P. Evans

Final approval of manuscript: Lisa R. Susswein, Cécile Skrzynia, Leslie A. Lange, Mark L. Graham III, James P. Evans

	ACKNOWLEDGMENTS

 
The support of Shelley Earp, MD, and the UNC Breast Cancer SPORE (P50-CA 58,233) have been invaluable in clinical cancer genetics at our institution.

	NOTES

 
This manuscript represents original work. A subset of the data included in this article was presented as posters at the American College of Medical Genetics Meeting, March 17-20, 2005, Dallas, TX, and at the 28th Annual San Antonio Breast Cancer Meeting, December 8-11, 2005, San Antonio, TX.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

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2. Gronwald J, Tung N, Foulkes WD, et al: Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update. Int J Cancer 118:2281-2284, 2006[CrossRef][Medline]

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4. Weitzel JN, McCaffrey SM, Nedelcu R, et al: Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Arch Surg 138:1323-1328, 2003[Abstract/Free Full Text]

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12. Thompson HS, Valdimarsdottir HB, Duteau-Buck C, et al: Psychosocial predictors of BRCA counseling and testing decisions among urban African-American women. Cancer Epidemiol Biomarkers Prev 11:1579-1585, 2002[Abstract/Free Full Text]

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Submitted January 3, 2007; accepted September 25, 2007.

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Susswein, L. R. Articles by Evans, J. P. Search for Related Content PubMed PubMed Citation Articles by Susswein, L. R. Articles by Evans, J. P.