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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, W. Y. Articles by Li, F. P. Search for Related Content PubMed PubMed Citation Articles by Chen, W. Y. Articles by Li, F. P.

BRCA1/2 Genetic Testing in the Community Setting

By Wendy Y. Chen, Judy E. Garber, Suzanne Higham, Katherine A. Schneider, Katie B. Davis, Amie M. Deffenbaugh, Thomas S. Frank, Rebecca S. Gelman, Frederick P. Li

From the Departments of Adult Oncology and Biostatistical Science, Dana-Farber Cancer Institute, and Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Clinical Operational Research Unit, University College London, London, United Kingdom; and Myriad Genetic Laboratories, Inc, Salt Lake City, UT.
Deceased.

Address reprint requests to Wendy Y. Chen, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email wendy_chen{at}dfci.harvard.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: BRCA1/2 genetic testing has been commercially available in the United States since 1996. Most published reports described BRCA1/2 testing as research studies at large academic centers, but less is known about testing in the community. This study evaluates the process and early outcomes of BRCA1/2 genetic testing as a clinical service in the community setting.

METHODS: Surveys were mailed to women in the United States whose health care providers ordered BRCA1/2 genetic testing from Myriad Genetic Laboratories from August 1998 through July 2000. Women tested at 149 large academic centers were excluded. Main outcome measures were demographic characteristics, recall of and satisfaction with the genetic testing process, and likelihood of pursuing cancer prevention strategies.

RESULTS: Among the 646 respondents, 414 (64%) had a personal history of cancer and 505 (78%) had at least one first-degree relative with breast and/or ovarian cancer. Most subjects (82%) recalled discussions of informed consent before testing (median time, 30 minutes). Genetic results were conveyed during an office visit (57%), by telephone (39%), or by mail (3%). More than 75% of respondents were "very satisfied with the counseling received." Cancer-free subjects with a germline mutation were more likely to consider prevention strategies after receiving the genetic results.

CONCLUSION: Virtually all respondents had a personal and/or family history of breast/ovarian cancer. Although pretest and posttest communications were not standardized, overall satisfaction with clinical breast cancer genetic testing was high. Additional follow-up will provide data on future cancer prevention practices and cancer incidence.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
BRCA1 AND BRCA2, the high-penetrance genes for hereditary cancers of the breast and other sites, were identified in 1994 and 1995, respectively.^1,2 Soon thereafter, several medical centers began BRCA1/2 genetic testing as part of research protocols.^3-5 While some groups proposed restricting testing to research settings,^6-9 Myriad Genetic Laboratories, Inc (Myriad), began offering BRCA1/2 testing as a clinical service ordered by health care providers for their patients. Most published studies have reported on BRCA1/2 testing through research protocols at academic institutions.^4,10-14

The availability of BRCA1/2 testing has raised concerns regarding informed consent, confidentiality, and genetic discrimination among physicians, patients and their families, ethicists, legislators, and the public.^9,15-18 BRCA1/2 testing can provide important information for cancer surveillance and prevention options.¹⁹ However, possible risks, such as emotional distress, family conflicts, and workplace or insurance discrimination, should also be addressed before testing.^18,20 Several states have passed legislation requiring written informed consent before genetic testing.¹⁷ Some experts have also warned against widespread testing for a gene with high penetrance but low prevalence.²¹ Our study was initiated to obtain data regarding the process and outcomes of BRCA1/2 testing in the community setting. This initial report of 646 subjects describes their demographic characteristics and examines their recall of the testing process, satisfaction with genetic testing, and intentions to pursue cancer prevention strategies.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Procedures
The BRCA1/2 Follow-up Study was established and funded through a sponsored research contract (principal investigator, F.P.L.) between Myriad and the Dana-Farber Cancer Institute to prospectively follow women tested outside of the academic setting for screening, chemoprevention practices, and cancer development. The research protocol was approved by the institutional review board of the Dana-Farber Cancer Institute. An external advisory committee comprising experts in cancer genetics, oncology, bioethics, and patient advocacy reviewed the design and conduct of the study. A Federal Certificate of Confidentiality was obtained to prevent involuntary disclosure of personal information on participants.

Myriad, the main source of BRCA1/2 clinical genetic testing in the United States, performed the laboratory analyses for all subjects in this study. All providers ordering genetic testing confirmed with their signature on the test requisition form that signed consent had been obtained and filed. Myriad offers three levels of genetic analyses at different charges: full-sequence analyses of one or both BRCA genes, Multisite 3 test for the three most common mutations in the Ashkenazi Jewish population, and single-site analysis for families with a previously identified BRCA1/2 mutation.²² The provider specifies the test to be performed.

Beginning in August 1998, we enrolled female subjects through health care providers in the United States who ordered BRCA1/2 genetic testing from Myriad as a clinical service. Although enrollment of new subjects continued through August 2001, only subjects enrolled through July 2000 were included in this current analysis. When BRCA1/2 test results were sent to providers, Myriad enclosed our study packet (cover letter, subject questionnaire, consent form, and opt-out card). Providers were asked to offer the study to their patients or decline by returning an opt-out card. Subjects entered the study by returning the completed questionnaire and signed consent form directly to us. Patients and providers who did not respond after two mailings were considered to have declined participation. Signed consent forms were stored in separate locked files. Questionnaires were identified only by subject identification numbers. Myriad provided BRCA1/2 genetic results that were linked through the study identification number to questionnaire responses only, but not personal identifiers. To assess selection bias, Myriad provided aggregate demographic data for women who were tested in the same time period but chose not to participate in our study.

Study Population
During the time interval for the present analysis, study packets were sent to 947 health care providers who ordered BRCA1/2 clinical testing for 2,080 women; 549 providers (58%) reported that they forwarded the packets to 1,364 patients. This report summarizes responses to the baseline questionnaire from the first 646 eligible respondents who returned the completed questionnaire and signed consent form before July 15, 2000. The remainder declined participation (406 subjects), completed the questionnaire but not the consent form (n = 29), were ineligible (n = 8), were lost to follow-up (n = 10), or had not responded as of March 31, 2001 (n = 265). In order to limit the study population to people tested in the community setting, providers and patients at 149 large academic centers in the United States assumed to have BRCA1/2 research protocols were excluded. Men were also excluded because of small numbers.

Survey Questionnaire
Sociodemographic and clinical data. Data were sought on age, race, religion, education, employment status, occupation, marital status, household income, current life and health insurance status and recent changes, cancer screening practices (mammograms, pelvic examinations, pap smears, pelvic ultrasounds), cancer prevention practices (prophylactic mastectomy/oophorectomy, chemoprevention), cancer history (age at diagnosis and current treatment), and family history of breast and/or ovarian cancer (relation and age at diagnosis). Pathology reports were not obtained for confirmation. Women were not specifically asked whether the tumor was in situ or invasive. Therefore, all women reporting a cancer diagnosis (in situ or invasive) were included in the cancer analyses.

Process of genetic testing.
Questions included identification of the health care provider who obtained informed consent, duration of counseling, source of payment for testing, and setting for delivery of the genetic results. Content of the pretest and posttest counseling sessions was not ascertained. Questions were based on those used in a follow-up study of patients who underwent retinoblastoma genetic testing²³ at the Genetic Risk Assessment Clinic at the Dana-Farber Cancer Institute.

Satisfaction with genetic testing.
A modification of the Shiloh satisfaction survey²⁴ was used, consisting of three subscales to assess the instrumental, affective, and procedural aspects of genetic counseling on a 4-point scale and a direct measure of overall satisfaction. The sum of the three subscales (Cronbach’s alpha = 0.90) and the summary question were highly correlated (r = 0.77), so the general question was used to assess overall satisfaction.

Attitudes toward genetic testing and intentions to pursue cancer prevention strategies.
Attitudes toward genetic testing were evaluated using 5-point Likert scales to assess agreement with statements regarding the testing experience. Table 1 shows the wording of the statements. Interest in cancer prevention strategies was assessed individually for mastectomy, oophorectomy, and chemoprevention. These items were based on questions used in a study of behavioral risk factors in women seeking genetic counseling²⁵ at the Dana-Farber Cancer Institute.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
The 646 study subjects received BRCA1/2 genetic testing through 379 health care providers. Two hundred eighty-six providers (75%) each contributed one subject to the study, 71 (19%) each enrolled two to four women, and 22 (6%) providers each added five to 20 cases. Median time interval from mailing of BRCA1/2 results and the study packet to providers until return of the completed questionnaire was 38 days. Distribution of age at testing, personal and family history of breast and/or ovarian cancer, and BRCA1/2 results were comparable for study participants and nonresponders (Table 2). Respondents resided throughout the United States and were primarily white (n = 608, 94%). The remainder were Asian (n = 11, 2%), African-American (n = 9, 1%), Hispanic (n = 7, 1%), or other/missing (n = 11, 2%). Median age at entry onto the study was 49 years (range, 23 to 90 years). Four hundred fifty-six (71%) identified themselves as Christian, 135 (21%) as Jewish, and 55 (9%) had another or no stated religious affiliation. Most were college educated (90%), married (78%), and employed outside of the home (64%). Median annual household income exceeded $75,000, although 77 respondents (12%) had household incomes of less than $35,000. All but two women had health insurance. Among 232 subjects without a personal history of cancer, only 15 never had a mammogram, and they were all under the age of 40. Among the 164 cancer-free women over age 40, 97% had had a mammogram within the past 2 years.

The most common reasons for seeking BRCA1/2 testing were (subjects could choose more than one): family history of cancer (n = 327, 51% of respondents), information for at-risk family members (n = 279, 43%), personal history of cancer (n = 127, 20%), medical decision making for cancer prevention (n = 122, 19%), and subjects’ peace of mind (n = 87, 13%).

Most respondents (n = 531, 82%) recalled discussing and reviewing the consent form with a health care provider, including genetic counselors (n = 319), physicians (n = 162, including 81 oncologists, 60 primary care providers, 11 surgeons, and 10 obstetrician/gynecologists), nurses (n = 41), or other providers (n = 9). Median time spent on counseling and informed consent was recalled to be 30 minutes (range, 1 to 240 minutes). Eighty-four respondents (13%) did not recall reviewing consent. The remaining 31 (5%) could not identify the provider who obtained consent or did not give a response. More than 75% of respondents indicated that they were "very satisfied with the counseling received" (highest rating on a 4-point scale), with no significant difference by BRCA1/2 results. Respondents also expressed satisfaction with specific aspects of genetic counseling, including provider expertise, sensitivity, and caring. A higher percentage of patients were satisfied (defined as 3 on a 4-point scale) when counseled by a physician or genetic counselor (P < .0001, Fisher’s exact test) or when more than 60 minutes were spent on counseling (P < .001, Fisher’s exact test).

Most BRCA1/2 genetic results were delivered during an office visit (n = 365, 57%) or by telephone (n = 253, 39%) (Table 4). Seventeen subjects (3%), including three with germline mutations, obtained their results by mail; 11 (2%) did not answer the question. Women with germline mutations and unclassified variants were more likely than women with negative results to receive their results during an office visit (P = .03) and to have results delivered by a physician or a genetic counselor (P = .001). Satisfaction did not differ whether results were delivered in person compared to by telephone or mail (P = .20).

Respondents were asked about the usefulness of genetic testing and reactions to their genetic results (Table 1). Among the 232 cancer-free respondents, the large majority agreed that "testing has been helpful for me to clarify my chances of getting cancer" (89%) and "knowing my results allows me to better plan for the future" (87%). Responses did not differ by BRCA1/2 results. However, respondents with germline BRCA1/2 mutations were more likely to agree that "finding out my results has been upsetting to me" and "knowing my results will help me prevent cancer." Women with cancer were asked the same questions regarding attitudes toward genetic testing, but many (ranging from 5% to 29% depending on the statement) chose "not applicable" rather than answer the question. Overall, their responses were similar to those of women without a history of cancer. In univariate and multivariable models (including geographic region, education level, questionnaire response time, and age at time of questionnaire return), genetic results were the only consistent predictive factors for their reactions toward the results and usefulness of genetic testing. Family history of cancer was not included in the multivariable models because the overwhelming majority of cancer-free respondents had a family history of cancer. As a summary measure of the BRCA testing experience, 98% of all respondents indicated, "I am glad that I participated in BRCA1 and 2 testing."

Among 232 cancer-free subjects, 34 (15%) had prior prophylactic or preventive procedures, including prophylactic mastectomy (n = 5), prophylactic oophorectomy (n = 25), chemoprevention (n = 1), both oophorectomy and mastectomy (n = 1), both chemoprevention and mastectomy (n = 1), or both chemoprevention and oophorectomy (n = 1). The remaining 198 were asked how genetic test results would influence their decision to pursue various cancer prevention strategies (Table 5). Those with a germline BRCA1/2 mutation were more likely to seek cancer chemoprevention (67%), prophylactic mastectomy (68%), and prophylactic oophorectomy (82%) than subjects with unclassified variants or negative results (P < .0001). Less than 5% of subjects with negative results were more likely to seek prophylactic surgery. Women with unclassified BRCA1/2 variants tended to be ambivalent, with some more likely to seek early interventions and others less. Additional stratification, by whether results were given in person or other approaches, yielded small numbers that were difficult to interpret.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
To our knowledge, this is the first study to describe the process of BRCA1/2 genetic testing as a clinical service in community settings throughout the United States. Virtually all published research studies on BRCA1/2 testing have focused on high-risk women enrolled onto research protocols at academic centers.^4,10-12,14 Our subjects shared many features with women tested at cancer risk clinics in academic centers. Both groups tended to be well educated and affluent and had personal and/or family histories of early-onset breast and/or ovarian cancers.^4,27 All but two women in our cohort had health insurance, which has previously been shown to be a strong predictor of uptake of genetic testing,⁴ since cost can be a deterrent for some women.²⁸ Our subjects were enrolled through 379 health care providers and better represent the experience of clinical BRCA1/2 genetic testing at diverse hospitals, clinics, and private practices within the United States. Most of the health care providers who enrolled women onto this study ordered genetic testing infrequently (fewer than three times during the 2-year study period), which suggests that these providers identified the women through their clinical practice rather than through cancer risk assessment clinics.

Our review of the literature showed that Armstrong et al²⁷ were the first to investigate clinical BRCA1/2 testing. Their study evaluated predictors of uptake of clinical BRCA1/2 testing among 251 women who attended the University of Pennsylvania Breast and Ovarian Cancer Risk Evaluation Program; 125 (50%) of them subsequently underwent testing. Compared with those who declined testing, subjects who had testing were more likely to be Ashkenazi Jewish, have a relative with a BRCA1 or 2 mutation, have a personal history of breast cancer and/or a higher predicted breast cancer risk. Unlike the women in the Armstrong study, our 646 subjects were recruited through 379 health care providers in practice outside of large academic centers and included only women who had already undergone genetic testing.

Within our series, 22% were found to have a germline BRCA1/2 mutation, and 16% had BRCA1/2 variants of unknown significance. Aggregate data on nonresponders yielded a similar distribution of BRCA1/2 results. Our cohort had higher frequencies of these alterations than some population-based series of breast cancer patients, including studies restricted to early-onset cases.^29-32 Also, the proportion of respondents with germline mutations in this cohort exceeded the 10% prior probability of carrying a BRCA1/2 mutation suggested as a guideline for consideration of genetic testing.³³ Therefore, genetic testing in the community setting was offered to a population with substantial likelihood for being a BRCA1/2 carrier.

The American Society of Clinical Oncology, American Society for Human Genetics, and other government and professional organizations have underscored the importance of counseling and informed consent before genetic testing.^6,7,33 Adherence to these guidelines in clinical practice is unknown. One study of clinical genetic testing for mutations in the adenomatous polyposis coli (APC) gene found that only 19% of 177 patients had received genetic counseling and only 17% had given written informed consent for testing.³⁴ Their findings underscored the importance of monitoring clinical genetic testing for hereditary cancers. In our series, most respondents recalled discussing informed consent before testing. Median time discussing consent was estimated to be 30 minutes. Data were not collected on specific items addressed during pretest and posttest counseling or participants’ knowledge of issues surrounding genetic testing. Approximately one half of them met with a genetic counselor; others discussed consent with nurses and physicians, including internists, oncologists, surgeons, and obstetrician/gynecologists. However, 84 respondents (13%) did not recall discussing consent. There might be several explanations for this finding, including failure of the physician to provide counseling, misinterpretation of informed consent to mean meeting with a genetic counselor, and forgetting that the discussion had occurred. These subjects did not differ from our other study subjects with regard to age at testing, personal and family history of cancer, or questionnaire response time.

Genetic test results were delivered during an office visit to 57% of the respondents. Women with germline mutations were more likely to receive their results in person. The others were informed by telephone, including 31% of women with germline mutations and 36% with unclassified variants; five of these women received their results by mail. Efforts to standardize and improve the clinical genetic testing process should focus not only on the eligibility and process of testing but also on follow-up after testing. Despite diverse approaches to pretest counseling and delivery of BRCA1/2 results, most subjects reported high satisfaction with the counseling, genetic testing, and disclosure processes.

Attitudes regarding the usefulness of genetic testing and emotional reactions to results were comparable among women with and without a personal history of cancer. However, one third of respondents with a history of cancer did not answer these questions, so comparisons between the two groups could be skewed by the missing data. Since it is not known whether women who failed to answer these questions felt more negatively or positively about their genetic testing experience, it would be difficult to predict how the missing data could potentially bias the results. As expected, women with germline mutations were more likely to be upset than those with unclassified variants or negative results. Genetic findings were stronger determinants of emotional reaction than personal cancer history, perhaps because the genetic information was new. Our results are consistent with prior studies that found more worry and depression among women at high breast cancer risk by linkage analysis or BRCA1/2 testing.^4,13,35,36 Also, as has been previously shown,¹³ adverse psychologic reactions may be more strongly related to genetic test results than to personal cancer history. Breast cancer–related anxiety and worry in women with a family history of breast cancer has been inversely associated with mammography adherence,^37,38 although Lerman et al³⁹ recently found that mammography utilization was unchanged among carriers after genetic testing while noncarriers decreased their screening rates. We intend to follow our subjects prospectively to ascertain the impact of genetic results on cancer screening.

Our cancer-free respondents with BRCA1/2 germline mutations reported greater likelihood than those with unclassified variants or negative results to pursue cancer prevention strategies such as prophylactic oophorectomy, mastectomy, or chemoprevention. Women with unclassified variants tended to be ambivalent, with some more likely to seek early interventions and others less. Attitudes among women with a history of cancer were similar except for chemoprevention, in which they were more likely to remain unchanged, perhaps because some of them were taking or had taken tamoxifen as part of their therapy. In one study of women in the United States who had undergone BRCA1/2 testing, 3% of BRCA1/2 carriers underwent a prophylactic mastectomy and 13% an oophorectomy within the first year after testing.³⁹ In contrast, 51% of women in Rotterdam with BRCA1/2 mutations underwent a prophylactic mastectomy and 64% underwent an oophorectomy.⁴⁰ The differences may be attributable to cultural differences, longer follow-up of the Dutch patients, availability of health insurance coverage for prophylactic procedures, and physician recommendations. Follow-up of our cohort will obtain data on the frequencies of prophylactic mastectomy, oophorectomy, and utilization of chemoprevention agents.

Since enrollment for this study occurred after the disclosure of genetic results, recall bias might have influenced our findings. However, BRCA1/2 results were not associated with level of recall of the consent process. Also, median time for questionnaire return was only 38 days and there were few late responders (> 100 days for receipt of completed questionnaire). Women who discussed genetic testing with their provider but declined testing were not captured in this study. Additionally, recruitment depended on the willingness of physicians to offer the study and women to complete the questionnaire. The response rate of 58% for health care providers is comparable to that of other studies relying on physician participation. It is possible that providers offered the questionnaire only to satisfied patients. Distributions of demographic characteristics, personal and family history of cancer, and BRCA1/2 results of our study participants were similar to those of women tested by Myriad during the same time period but who declined participation. Therefore, our population was likely representative of women who had testing in the community setting with regard to those variables, although the generalizability of their counseling and psychosocial experiences is not known.

Other limitations of our data include the potential for varied interpretations of some of the questions by the respondents and lack of explanations for their answers. Also, many study subjects with a history of cancer elected not to answer certain questions. Follow-up questionnaires will be modified to gather more detailed data with the use of both structured and open-ended questions.

The availability of BRCA1/2 genetic testing has created the need to understand the characteristics of these patients and the process and outcomes of genetic testing. This report differs from prior studies because subjects were recruited beyond academic centers with research interests in BRCA1/2 testing, and it provides unique preliminary data on a large prospective cohort of women undergoing testing in the community. Nearly all women in our cohort had a personal and/or family history of breast cancer. These findings, together with the mutation frequency in both responders and nonresponders to our questionnaire, suggest that physicians ordering BRCA1/2 clinical genetic testing are testing women with a higher probability of being a carrier. Most women recalled discussing informed consent and many also met with a genetic counselor. Despite diverse approaches to counseling, overall satisfaction with the genetic testing process was high. Additional follow-up will provide data on cancer screening behaviors, lifestyle modifications, rates of prophylactic surgery and chemoprevention use, and cancer incidence.

	ACKNOWLEDGMENTS

 
Supported in part by a sponsored research contract from Myriad Genetic Laboratories, Inc (principal investigator, F.P.L.). F.P.L. is supported in part by a Harry and Elsa Jiler Clinical Research Professorship from the American Cancer Society. R.S.G. is supported in part by research grant no. CA06516 from the National Institutes of Health.

We acknowledge the guidance of the members of the advisory committee for this study, as well as the support of multiple physicians, genetic counselors, nurses, and their office staff who helped recruit study subjects.

	NOTES

 
Myriad staff assisted in the recruitment procedures, questionnaire distribution, and database creation but not in data analysis or interpretation.

Preliminary data on a subset of study subjects were presented at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
1. Miki Y, Swensen J, Shattuck-Eidens D, et al: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 66-71, 1994[Abstract/Free Full Text]

2. Wooster R, Bignell G, Lancaster J, et al: Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789-792, 1995[CrossRef][Medline]

3. Futreal PA, Liu Q, Shattuck-Eidens D, et al: BRCA1 mutations in primary breast and ovarian carcinomas. Science 266: 120-122, 1994[Abstract/Free Full Text]

4. Lerman C, Narod S, Schulman K, et al: BRCA1 testing in families with hereditary breast-ovarian cancer: A prospective study of patient decision making and outcomes. JAMA 275: 1885-1892, 1996[Abstract]

5. Couch FJ, DeShano ML, Blackwood MA, et al: BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 336: 1409-1415, 1997[Abstract/Free Full Text]

6. Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet 55:i-iv, 1994

7. Statement on use of DNA testing for presymptomatic identification of cancer risk: National Advisory Council for Human Genome Research. JAMA 271:785, 1994

8. Hoskins KF, Stopfer JE, Calzone KA, et al: Assessment and counseling for women with a family history of breast cancer: A guide for clinicians. JAMA 273: 577-585, 1995[Abstract]

9. Collins FS: BRCA1: Lots of mutations, lots of dilemmas. N Engl J Med 334: 186-188, 1996[Free Full Text]

10. Botkin JR, Croyle RT, Smith KR, et al: A model protocol for evaluating the behavioral and psychosocial effects of BRCA1 testing. J Natl Cancer Inst 88: 872-882, 1996[Free Full Text]

11. Lloyd S, Watson M, Waites B, et al: Familial breast cancer: A controlled study of risk perception, psychological morbidity and health beliefs in women attending for genetic counselling. Br J Cancer 74: 482-487, 1996[Medline]

12. Audrain J, Rimer B, Cella D, et al: Genetic counseling and testing for breast-ovarian cancer susceptibility: What do women want? J Clin Oncol 16: 133-138, 1998[Abstract/Free Full Text]

13. Lerman C, Hughes C, Lemon SJ, et al: What you don’t know can hurt you: Adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing. J Clin Oncol 16: 1650-1654, 1998[Abstract]

14. Biesecker BB, Ishibe N, Hadley DW, et al: Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families. Am J Med Genet 93: 257-263, 2000[CrossRef][Medline]

15. Points to consider: Ethical, legal, and psychosocial implications of genetic testing in children and adolescents—American Society of Human Genetics Board of Directors, American College of Medical Genetics Board of Directors. Am J Hum Genet 57:1233-1241, 1995

16. Visco F: Commentary on the ASCO statement on genetic testing for cancer. J Clin Oncol 14: 1737, 1996

17. Rothenberg K, Fuller B, Rothstein M, et al: Genetic information and the workplace: Legislative approaches and policy changes. Science 275: 1755-1757, 1997[Free Full Text]

18. Kodish E, Wiesner GL, Mehlman M, et al: Genetic testing for cancer risk: How to reconcile the conflicts. JAMA 279: 179-181, 1998[Free Full Text]

19. Burke W, Daly M, Garber J, et al: Recommendations for follow-up care of individuals with an inherited predisposition to cancer: II. BRCA1 and BRCA2—Cancer Genetics Studies Consortium. JAMA 277: 997-1003, 1997[Abstract]

20. Weber B: Breast cancer susceptibility genes: Current challenges and future promises. Ann Intern Med 124: 1088-1090, 1996[Free Full Text]

21. Couch FJ, Hartmann LC: BRCA1 testing: Advances and retreats. JAMA 279: 955-957, 1998[Free Full Text]

22. Myriad Genetic Laboratories: BRCA Analysis Test Request Form. Salt Lake City UT, Myriad Genetic Laboratories, 1999

23. Cohen JG, Dryja TP, Davis KB, et al: RB1 genetic testing as a clinical service: A follow-up study. Med Pediatr Oncol 37: 372-378, 2001[CrossRef][Medline]

24. Shiloh S, Avdor O, Goodman RM: Satisfaction with genetic counseling: Dimensions and measurement. Am J Med Genet 37: 522-529, 1990[CrossRef][Medline]

25. Emmons KM, Kalkbrenner KJ, Klar N, et al: Behavioral risk factors among women presenting for genetic testing. Cancer Epidemiol Biomarkers Prev 9: 89-94, 2000[Abstract/Free Full Text]

26. Ries L, Eisner M, Kosary C, et al: SEER Cancer Statistics Review, 1973-1999. Bethesda MD, National Cancer Institute, 2002

27. Armstrong K, Calzone K, Stopfer J, et al: Factors associated with decisions about clinical BRCA1/2 testing. Cancer Epidemiol Biomarkers Prev 9: 1251-1254, 2000[Abstract/Free Full Text]

28. Durfy SJ, Bowen DJ, McTiernan A, et al: Attitudes and interest in genetic testing for breast and ovarian cancer susceptibility in diverse groups of women in western Washington. Cancer Epidemiol Biomarkers Prev 8: 369-375, 1999[Abstract/Free Full Text]

29. Langston AA, Malone KE, Thompson JD, et al: BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med 334: 137-142, 1996[Abstract/Free Full Text]

30. Newman B, Mu H, Butler LM, et al: Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 279: 915-921, 1998[Abstract/Free Full Text]

31. Malone KE, Daling JR, Neal C, et al: Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 88: 1393-1402, 2000[CrossRef][Medline]

32. Syrjakoski K, Vahteristo P, Eerola H, et al: Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients. J Natl Cancer Inst 92: 1529-1531, 2000[Free Full Text]

33. Statement of the American Society of Clinical Oncology genetic testing for cancer susceptibility. J Clin Oncol 14:1730-1736; discussion 1737-1740, 1996

34. Giardiello FM, Brensinger JD, Petersen GM, et al: The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N Engl J Med 336: 823-827, 1997[Abstract/Free Full Text]

35. Lynch HT, Lemon SJ, Durham C, et al: A descriptive study of BRCA1 testing and reactions to disclosure of test results. Cancer 79: 2219-2228, 1997[CrossRef][Medline]

36. Croyle RT, Smith KR, Botkin JR, et al: Psychological responses to BRCA1 mutation testing: Preliminary findings. Health Psychol 16: 63-72, 1997[CrossRef][Medline]

37. Kash KM, Holland JC, Halper MS, et al: Psychological distress and surveillance behaviors of women with a family history of breast cancer. J Natl Cancer Inst 84: 24-30, 1992[Abstract/Free Full Text]

38. Lerman C, Daly M, Sands C, et al: Mammography adherence and psychological distress among women at risk for breast cancer. J Natl Cancer Inst 85: 1074-1080, 1993[Abstract/Free Full Text]

39. Lerman C, Hughes C, Croyle RT, et al: Prophylactic surgery decisions and surveillance practices one year following BRCA1/2 testing. Prev Med 31: 75-80, 2000[CrossRef][Medline]

40. Meijers-Heijboer EJ, Verhoog LC, Brekelmans CT, et al: Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 355: 2015-2020, 2000[CrossRef][Medline]

Submitted August 24, 2001; accepted July 26, 2002.

This article has been cited by other articles:

				E. M. John, A. Miron, G. Gong, A. I. Phipps, A. Felberg, F. P. Li, D. W. West, and A. S. Whittemore Prevalence of Pathogenic BRCA1 Mutation Carriers in 5 US Racial/Ethnic Groups JAMA, December 26, 2007; 298(24): 2869 - 2876. [Abstract] [Full Text] [PDF]

				S. T. Vadaparampil, L. Wideroff, N. Breen, and E. Trapido The Impact of Acculturation on Awareness of Genetic Testing for Increased Cancer Risk among Hispanics in the Year 2000 National Health Interview Survey. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 618 - 623. [Abstract] [Full Text] [PDF]

				K. Armstrong, E. Micco, A. Carney, J. Stopfer, and M. Putt Racial Differences in the Use of BRCA1/2 Testing Among Women With a Family History of Breast or Ovarian Cancer JAMA, April 13, 2005; 293(14): 1729 - 1736. [Abstract] [Full Text] [PDF]

				R. L. Milne, J. A. Knight, E. M. John, G. S. Dite, R. Balbuena, A. Ziogas, I. L. Andrulis, D. W. West, F. P. Li, M. C. Southey, et al. Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 350 - 356. [Abstract] [Full Text] [PDF]

				A. S. Whittemore, G. Gong, E. M. John, V. McGuire, F. P. Li, K. L. Ostrow, R. DiCioccio, A. Felberg, and D. W. West Prevalence of BRCA1 Mutation Carriers among U.S. Non-Hispanic Whites Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2078 - 2083. [Abstract] [Full Text] [PDF]

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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, W. Y. Articles by Li, F. P. Search for Related Content PubMed PubMed Citation Articles by Chen, W. Y. Articles by Li, F. P.