2 Testing Among U.S. Primary Care Physicians

Awareness and Utilization of BRCA1/2 Testing Among U.S. Primary Care Physicians Cecelia A. Bellcross, PhD, Katherine Kolor, PhD, Katrina A.B. Goddard, PhD, Ralph J. Coates, PhD, Michele Reyes, PhD, Muin J. Khoury, MD, PhD Background: Testing for mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 (BRCA) has been commercially available since 1996. Purpose: This study sought to determine, among U.S. primary care physicians, the level of awareness and utilization of BRCA testing and the 2005 U.S. Preventive Services Task Force (USPSTF) recommendations. Methods: In 2009, data were analyzed on 1500 physician respondents to the 2007 DocStyles national survey (515 family practitioners, 485 internists, 250 pediatricians, and 250 obstetricians/ gynecologists).

Results: Overall, 87% of physicians were aware of BRCA testing, and 25% reported having ordered testing for at least one patient in the past year. Ordering tests was most prevalent among obstetricians/gynecologists in practice for more than 10 years, with more affluent patients. Physicians were asked to select indications for BRCA testing from seven different clinical scenarios representing increased (4) or low-risk (3) situations consistent with the USPSTF guidelines. Among ordering physicians (pediatricians excluded), 45% chose at least one low-risk scenario as an indication for BRCA testing. Only 19% correctly selected all of the increased-risk and none of the low-risk scenarios. Conclusions: A substantial majority of primary care physicians are aware of BRCA testing and many report having ordered at least one test within the past year. A minority, however, appear to consistently recognize the family history patterns identifıed by the USPSTF as appropriate indications for BRCA evaluation. These results suggest the need to improve providers’ knowledge about existing recommendations—particularly in this era of increased BRCA direct-to-consumer marketing. (Am J Prev Med 2011;40(1):61– 66) © 2011 American Journal of Preventive Medicine

Introduction

A

lthough there has been a steady increase in availability and application of predictive genetic tests during the past decade, there exist few evidencebased recommendations guiding use of these tests in clinical practice. One exception is clinical testing for mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 (BRCA). It is estimated1–3 that 2%–7% of breast cancers and 10%–15% of ovarian cancers are the result of a dominantly inherited mutation in one of these genes. In 2005, the U.S. Preventive Services From the Offıce of Public Health Genomics, CDC (Bellcross, Kolor, Coates, Reyes, Khoury), Atlanta, Georgia; and Center for Health Research (Goddard), Kaiser Permanente, Portland, Oregon Address correspondence to: Cecelia A. Bellcross, PhD, Offıce of Public Health Genomics, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS E-61, Atlanta GA 30333. E-mail: [email protected]. 0749-3797/$17.00 doi: 10.1016/j.amepre.2010.09.027

© 2011 American Journal of Preventive Medicine. All rights reserved.

Task Force (USPSTF) released a recommendation titled “Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility.”4 The recommendation, based on a systematic evidence review,5 came 9 years after clinical testing became available. Focused on women without a personal history of breast or ovarian cancer, the USPSTF4 recommended that “women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing.” At the same time, the USPSTF recommended against routine referral for women without an increased-risk family history, concluding that the potential harms under these circumstances outweigh the benefıts.4 Although acknowledging that there are no standardized referral criteria, the USPSTF outlined specifıc family history patterns associated with an increased risk for deleterious mutations in the BRCA1 or BRCA2 genes. In addition, the USPSTF indicated that individuals Am J Prev Med 2011;40(1)61– 66 61

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from families with a known BRCA mutation should routinely be referred for genetic counseling. Despite growing evidence of clinical utility,6 –10 and the endorsement of BRCA testing by many professional organizations,11–16 the extent to which primary care clinicians are actually ordering testing or making genetic referrals and how they identify appropriate individuals for these services is still poorly understood. To our knowledge, the present study is the fırst to assess provider awareness and use of BRCA testing since the USPSTF recommendations were published. The data presented here, obtained from DocStyles—a national survey of physicians in the U.S.—also addresses primary care providers’ knowledge of the family history patterns considered by the USPSTF as appropriate indications for genetic counseling referral and evaluation for BRCA testing.

Methods Study Design During July and August 2007, Porter Novelli, a public relations fırm that has a specialty practice in health and social marketing, conducted DocStyles–a web-based survey of primary care physicians in the following specialties: family practice, internal medicine, pediatrics, and obstetrics– gynecology (ob– gyn). Porter Novelli determines the type of providers recruited and the relative proportion of each. Survey questions are submitted for inclusion on a variety of topics from several different investigators. The DocStyles sample was drawn from the Epocrates Honors Panel, an opt-in, verifıed panel of 142,000 physicians. Verifıcation was achieved by checking each physician’s fırst and last name, date of birth, medical school, and graduation date against the American Medical Association’s (AMA’s) master fıle at the time of panel registration. A random sample of 3115 physicians was invited to participate in DocStyles. This sample was drawn to match AMA master fıle proportions for age, gender, and region. Physicians were paid an honorarium of $45–$55 for completing the survey. Of those invited, 1502 completed the entire survey—a response rate of 48%. The CDC licenses the results of the DocStyles survey from Porter Novelli. Analysis of these results was exempt from IRB approval because personal identifıers were not included in the data provided to the CDC.

Survey Items Standard DocStyles survey items include physician demographic characteristics of gender, age, and race/ethnicity. Physician practice parameters of specialty, patients seen per week, years of practice, practice setting, and patient SES are also routinely collected. For the current study, the CDC submitted targeted questions regarding BRCA testing for inclusion in the survey. Respondents were asked whether they had ordered BRCA1&2 testing: to determine if a person has or is likely to develop breast or ovarian cancer for at least one patient in the past year. Respondents were then asked, Under which of the following circumstances is BRCA1&2 genetic testing indicated? Respondents who answered either, I am not aware of BRCA1&2 testing or None of the above, were excluded

from selecting any of the seven clinical scenarios given. Four of these scenarios represented increased risk, and three represented low-risk family history patterns with respect to likelihood of association with a BRCA mutation. The specifıc scenarios and their relationship to the USPSTF guidelines are given in Table 1. Because of space constraints, there were no separate questions asked regarding referral for genetic counseling or provision of recommended pre- and post-test counseling. In this context, therefore, ordering testing may include both physicians who did and those who did not ensure adequate genetic counseling was performed, either by themselves or by referral to an adequately trained healthcare provider.

Statistical Analyses We used SPSS, version 17.0, for all statistical analyses, which were completed in 2009. Bivariate analysis of categoric variables was performed using the chi-square test (unadjusted). Given their limited involvement with patients dealing with BRCA issues, pediatricians were excluded from subsequent analyses. Unadjusted chisquare tests were also used to compare selection of clinical scenarios between clinicians who were aware of BRCA testing but had not ordered a test in the past year, and those who had ordered testing.

Results Of the 1500 physician respondents, 1300 (87%) were aware of BRCA testing and 375 (25%) reported having ordered at least one test in the past year. Exclusion of pediatricians (n⫽250) increased these percentages to 93% aware and 30% ordered. Characteristics of all respondents, by awareness and ordering of BRCA testing, are given in Table 2. Ob– gyns were the most likely to be aware of (100%) and to have ordered testing (62%), whereas pediatricians were the least likely (53% aware, 1.2% ordered). In addition, physicians who reported awareness of BRCA testing were more likely to be female, aged ⱕ40 years, to see more than 100 patients per week, and to have been in practice 10 years or less (p⬍0.001 for all comparisons). Physicians who reported having ordered testing were also more likely to be female and younger. However, they were more likely to have been in practice for longer than 10 years and serve patients in the upper three SES categories. Analysis of the selection of clinical scenarios as indications for BRCA testing, which omits pediatricians, is illustrated in Figure 1. At least one low-risk scenario was chosen by 39% of physicians who were aware of testing (but had not ordered) and 45% who had ordered BRCA testing for at least one patient in the past year. Each of the increased-risk scenarios was signifıcantly more likely to have been selected by physicians who reported having ordered BRCA testing, in comparison to those who were aware of, but had not ordered, testing. A minority of physicians (15% aware, 19% ordered) selected all four of www.ajpm-online.net

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Table 1. Survey clinical scenarios and relationship to USPSTF guidelines

Clinical scenario

USPSTF identified consideration for referral/testing; comments

Risk levela

1. Any adult woman with breast cancer

Low

No

2. Any adult woman with any family history of breast cancer

Low

No

3. Any adult woman with any family history of ovarian cancer

Low

No

4. Any adult woman with a family history of breast cancer, including at least three affected close relatives

Increased

Yes; USPSTF identified increased-risk family history pattern: “a combination of three or more first or second degree relatives with breast cancer regardless of age”

5. A close adult female relative of a person who has tested positive for a BRCA1 or BRCA2 mutation

Increased

Yes; the USPSTF indicated that “these women should be referred for genetic counseling”

Increased

Yes; USPSTF identified increased-risk family history pattern: “two first degree relatives with breast cancer, one of whom received the diagnosis at age 50 years or younger”

Increased

Yes—indirectly; guidelines specifically not directed toward women who have a diagnosis of breast cancer, however, “a first-degree relative with bilateral breast cancer” was one of the increasedrisk family history patterns specified by the USPSTF

6. Any adult woman with ⱖ2 first-degree relatives with breast cancer and ⱖ1 relative diagnosed at age ⬍50 years

7. Any adult woman with multiple primary breast cancers

a

Refers to likelihood of association with a BRCA mutation USPSTF, U.S. Preventive Services Task Force

the increased-risk scenarios and none of the low-risk scenarios, as indications for BRCA testing. A substantially lower proportion of physicians selected the last increased-risk scenario (Scenario 7: any woman with multiple primary breast cancers) compared to the other three (40% vs 60%– 68% aware, 49% vs 72%–78% ordered). Scenario 7 was only indirectly consistent with the USPSTF guidelines, as it referred to a woman with breast cancer (as opposed to a family member) and used the term “multiple primary” versus “bilateral breast cancer.” When this scenario was excluded, the percentage of respondents selecting all of the increased-risk, but none of the low-risk, scenarios increased for both physicians aware of testing (25%) and those who had ordered (31%).

Discussion The results of this national survey indicate that most primary care physicians are aware of BRCA testing, and many have ordered testing for at least one patient within the past year. Table 3 (available online at www.ajpmonline.net) provides a summary of previous published surveys addressing awareness and use of BRCA testing among U.S. clinicians—all of which were completed prior to release of the 2005 USPSTF recommendations.17–23 The current results suggest a relatively substantial increase in test usage, particularly in comparison to the most analogous study by Wideroff in 2000, where only January 2011

6% of all primary care providers (ob– gyn, family/general practice, internal medicine) had ordered a “breast/ovarian cancer susceptibility test” in the past year.20 The extent to which this apparent increase is related to the USPSTF guidelines, or other factors such as intensifıed commercial marketing of BRCA testing, remains to be explored. Although the current data suggest that utilization of BRCA testing has risen, it also was found that many physicians may not recognize the increased-risk family history patterns suggested by the USPSTF as appropriate indications for BRCA evaluation. Less than one fıfth of physicians correctly identifıed all of the increased- and low-risk scenarios. Close to half of ordering clinicians selected at least one low-risk scenario as an indication for testing, the most common being “any adult woman with any family history of breast cancer” (Scenario 2). The USPSTF specifıcally recommended against routine referral or testing of low-risk women, citing evidence of harms outweighing benefıts.4 It is also noteworthy that one third of physicians aware of BRCA testing, and one quarter of those who had ordered testing, did not select the two scenarios most likely to be associated with presence of a BRCA mutation: a close relative with a known mutation (Scenario 5) and two or more fırst-degree relatives with breast cancer, at least one diagnosed under age 50 years (Scenario 6). Although it could be argued that these fındings are related to selective preference for other screening criteria, rather

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than physician knowledge of the USPSTF recommendations, it should be noted that low-risk scenarios 1 and 2 are not found in major published protocols,12–16 whereas increased-risk scenarios 5 and 6 are typically included. Several limitations of the present study deserve consideration and should be addressed in future surveys on this topic. Because of the DocStyles sampling methodology, which draws from a self-selected group (Epocrates Honor Panel), the respondents may not be truly representative of primary care providers in the U.S. Although BRCA testing is not recommended for minors, pediatricians were included in the initial bivariate analyses to provide a basis for comparison, and it is noteworthy that a majority were aware of testing. With respect to direct reflection of knowledge of the USPSTF guidelines, the survey asked about indications for “testing” as opposed to indications for “referral for genetic counseling and evaluation for BRCA testing” as specifıed by the USPSTF. It is possible that some clinicians, who did not report ordering

Table 2. Characteristics of physician respondents by awareness and ordering of BRCA testing, n (%) unless otherwise indicated

Characteristic

Total

Aware of BRCA testinga

Ordered BRCA testingb

Overall

1500

1300 (87.7)

375 (25.0)

Female (ref)

536

495 (92.4)

158 (29.5)

Male

964

805 (83.5*)

217 (22.5**)

Family/general practice (ref)

515

462 (89.7)

112 (21.8)

Internist

485

455 (93.8***)

106 (21.9)

Pediatrician

250

133 (53.2*)

Obstetrician/gynecologist

250

250 (100*)

154 (61.6*)

ⱕ40 (ref)

609

549 (90.2)

134 (22.0)

⬎40

891

751 (84.3*)

241 (27.1***)

1110

956 (86.1)

275 (24.8)

Black

50

44 (88.0)

14 (28.0)

Asian

265

238 (89.8)

68 (25.7)

Other

75

62 (82.6)

18 (24.0)

ⱕ100 (ref)

795

711 (89.4)

192 (24.2)

⬎100

705

589 (83.6*)

183 (26.0)

ⱕ10 (ref)

645

581 (90.1)

140 (21.7)

⬎10

855

719 (84.1*)

235 (27.5**)

288

249 (86.5)

82 (28.5)

1022

890 (87.1)

254 (24.9)

190

161 (84.7)

39 (20.5)

48

41 (85.4)

4 (8.3)

Poor–lower middle

188

157 (83.5)

31 (13.5)

Lower middle–middle

549

483 (88.0)

147 (26.8**)

Middle–upper middle

640

554 (86.6)

174 (27.2**)

75

65 (86.7)

Gender

Specialty

3 (1.2*)

Age (years)

Race/ethnicityc White (ref)

Patients per week

Years of practice

Practice setting Individual (ref) Group Hospital Patient SES Very poor–poor (ref)

Upper middle–affluent

19 (25.3***)

Note: Unadjusted ␹2 test for categoric variables compared to referent group: *pⱕ0.001 (bolded), **pⱕ0.01 (bolded), ***p⬍0.05 (bolded) a Includes those having ordered testing b At least one test within the past year c Hispanic ethnicity included within race categories, n⫽59

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Despite these limitations, the current study is the fırst to examine use of BRCA testing among U.S. primary care providers since the USPSTF recommendations were released. The present study also reveals potentially important information regarding provider’s perceptions of the appropriateness of BRCA testing in specifıc clinical situations. Although many clinicians recognized at least some increasedFigure 1. Selection of clinical scenarios by physicians aware of and having ordered BRCA risk scenarios, there testing (pediatricians excluded), unadjusted ␹2, ordered vs aware remains evidence of *pⱕ0.001, **p⬍0.05 under-recognition of those at most intesting, did provide counseling or refer patients for genetic creased risk, and the potential for overuse of BRCA testservices for given scenarios. Further, as the survey did not ing among patients in low-risk situations. delineate specifıcally between ordering BRCA testing diIn light of the current data, and given the increased rectly or in collaboration with genetic services, these results direct-to-consumer marketing of BRCA testing, efforts should not be taken to imply that more physicians are orderdirected toward improving clinician understanding of ing testing directly without ensuring appropriate pre- and BRCA testing and the USPSTF recommendations appear post-test counseling. It should be stressed that the majority warranted. Further research is needed to better compreof existing guidelines and professional organization statehend why primary care physicians may select given clinments regarding BRCA testing recommend genetic counselical scenarios for BRCA testing, and what interventions ing by an adequately trained individual.4,12–16 may be most effective in increasing the appropriateness To address this issue, future studies should examine of these practices. Studies validating specifıc family hisboth direct ordering and patterns of referral to genetic tory screening guidelines and criteria will be also be critservices, and the extent to which individuals appropriical. Such research will be essential to the development of ately trained in cancer genetics are providing pre- and/or informed and targeted educational programs to ensure post-test counseling. Finally, as not all of the increasedpublic health benefıt from appropriate BRCA testing and risk scenarios used the direct wording of the USPSTF related cancer risk–management strategies. guidelines, some clinicians may not have recognized them as such. This possibility is suggested by the substantially lower rate of selection of the criterion of “any woman with multiple primary breast cancers.” To more directly assess knowledge of the USPSTF recommendations in future surveys, questions may need to focus specifıcally on whether or not clinicians have heard of or read the guidelines and if they are able to correctly identify the actual increased-risk scenarios given. It would also be important to determine if ordering clinicians do, or do not, agree with the USPSTF criteria for “increased risk,” or whether they may be following alternate guidelines or institutional protocols. January 2011

The fındings and conclusions in this report are those of the authors and do not necessarily represent the offıcial position of the CDC. No fınancial disclosures were reported by the authors of this paper.

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Appendix Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.amepre.2010.09.027.

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