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Attitudes of obstetrician-gynecologists toward DNA testing for a genetic susceptibility to breast cancer
Attitudes of Obstetrician-Gynecologists Toward D N A Testing for a Genetic Susceptibility to Breast Cancer PETER T. ROWLEY, MD, AND STARLENE LOADER, BA Objective: To assess knowledge and attitudes of area obstetrician-gynecologists toward DNA testing for genetic susceptibility to breast cancer. Methods: At a staff meeting of each of the Rochester area's hospitals that had an obstetric service, we assessed knowledge of inherited predisposition to breast cancer, presented the current status of testing for genetic susceptibility, and assessed attitudes toward such testing. Results: The majority of the physicians surveyed believed that current BRCA1 testing can detect a genetic predisposition to breast cancer accurately enough to be clinically useful (81%) and that a young woman with a family history of breast cancer not currently having regular mammography is likely to benefit from DNA testing because a positive result may motivate her to start mammography earlier (88%). However, most respondents thought that women who test positive are likely to be excessively anxious (87%) and may be discriminated against for insurance purposes (75%). In response to an invitation to participate in a clinical trial of free BRCA1 screening, 74 (70%) desired to participate. Conclusion: Obstetrician-gynecologists expect women detected to have a BRCA1 mutation to be motivated to conduct surveillance, but also to experience anxiety and possible discrimination. (Obstet Gynecol 1996"88.'611-5)
In 1990, a genetic locus for breast cancer susceptibility, BRCA1, was identified on the long arm of chromosome 17.1 In 1994, the cloning of the BRCA1 gene was reported. 2 The gene was identified by the finding that it was mutated in the affected members of families with breast and ovarian cancer, but not in unaffected individuals. Until March 1996, at least 100 different mutations in affected families have been found. 3 Individuals with a BRCA1 mutation have an 82% risk of developing breast cancer by age 70 and often have an earlier age of onset than individuals from breast-cancer families with-
From the Department of Medicine and the Division of Genetics, University of Rochester School of Medicine, Rochester. New York.
VOL. 88, NO. 4 (PART 1), OCTOBER 1996
out a BRCAI mutation. 4 It has been estimated indirectly that one in 833 w o m e n have a BRCA1 mutation, s We are planning to conduct a pilot study of DNA screening for BRCA1 mutations to determine whether or not w o m e n with a positive family history benefit. This study will involve 1) identifying w o m e n with a positive family history of breast cancer, 2) offering BRCA1 testing, 3) explaining the result, and 4) assessing its impact, both its positive effects (increased understanding, adoption of early detection measures, or reassurance) and its potential negative effects (anxiety, stigmatization, and discrimination as partner, insuree, or employee). To ensure that our trial would identify outcomes likely to occur when such testing is adopted as a service, rather than as a research effort, we wished to have w o m e n learn about the program through their own physicians. Obstetrician-gynecologists are more likely to refer w o m e n for m a m m o g r a p h y than are internists. 6 Hence, the first step was to assess the attitudes of area obstetrician-gynecologists to such testing. We here rep o r t the attitudes of the s u r v e y e d obstetriciangynecologists toward DNA testing for a genetic susceptibility to breast cancer.
Materials and Methods Between October 1994 and February 1995, presentations were m a d e at the regular staff conferences of all five Rochester hospitals having obstetric services. At the beginning of each conference, a questionnaire was a d m i n i s t e r e d to assess the staff's current breastscreening practices and their knowledge of inherited predisposition to breast cancer. Next, a 30- to 40-minute explanation was given of the magnitude of the breast-cancer problem, the clinical characteristics of the familial form, the relevant facts about BRCA1, and the design of the proposed clinical
0029-7844/96/$15.00 611 PII S0029-7844(96)00199-8
trial. It w a s a d m i t t e d that only 30-50% of families with multiple cases of breast cancer h a v e m u t a t i o n s in BRCA1, s that there is no clinically available test to identify the responsible m u t a t i o n in m o s t of the remaining families, and that there is no intervention to recomm e n d to those f o u n d to have a BRCA1 m u t a t i o n that will eliminate the risk of d y i n g from breast or ovarian cancer. Questions about the material presented were answered. Finally, a second questionnaire w a s administered to the physicians to assess attitudes t o w a r d BRCA1 testing to determine w h e t h e r they w i s h e d to participate in this clinical trial. Of the 124 area prenatal care providers, a total of 69 were present at the beginning of one of the conferences and completed the k n o w l e d g e questionnaire, and 105 were present for the presentation itself and completed the attitude questionnaire at the end of one of the conferences. This project was a p p r o v e d by the University of Rochester Research Subjects Review Board.
Results The physicians' responses regarding early detection of breast cancer are s h o w n in Table 1. The p r o p o r t i o n agreeing strongly or agreeing s o m e w h a t with the statem e n t that physician breast examination is an effective m e a n s for the early detection of breast cancer was 44 of 69 or 71%. The s a m e belief a b o u t breast self-examination w a s held by 73.9%, w h e r e a s the same belief about annual m a m m o g r a p h y was held by a larger percentage, 91.3%. Most physicians r e c o m m e n d e d annual physician examination beginning at age 20 (85.6%) and regular self-examination starting either at age 20 (65.3%) or age 30 (27.5%), but they were d i v i d e d a b o u t the age for starting annual m a m m o g r a p h y b e t w e e n ages 40 (53.6%) and 50 (45%). Thus, in terms of effectiveness as a m e a n s for the early detection of breast cancer, r e s p o n d e n t s r a n k e d a n n u a l m a m m o g r a p h y first, m o n t h l y selfexamination second, and annual examination by a physician third (Table 1). Despite rating m a m m o g r a p h y as m o s t effective, only 31.9% w o u l d m a k e an appointm e n t for the n o n c o m p l i a n t patient. The physicians' k n o w l e d g e of inherited predisposition to breast cancer w a s also briefly assessed. The largest n u m b e r g a v e the correct a n s w e r for the percentage of breast cancer patients w h o are believed to have an inherited predisposition thereto, ie, 10%. 7 The majority also recognized that the type of t u m o r c o m m o n l y f o u n d in families with breast cancer is ovarian cancer (78.5%). The majority correctly identified an early age of onset (52 of 69, 75.4%) and a d o m i n a n t inheritance pattern (60.9%) as characteristic features. The majority also r e c o g n i z e d that transmission t h r o u g h females only a n d characteristic histologic a p p e a r a n c e are not lea612
R o w l e y and Loader
BreastCancer Genetic Testing
Table 1. Responses Before Explanation About BRCA1
Testing (N = 69) Item
Response
Current practice regarding early detection of breast cancer Annual physician breast examination is an effective means for the early detection of breast cancer Agree Disagree Neither Monthly self-examination is an effective means for the early detection of breast cancer Agree Disagree Neither Annual mammography is an effective means for the early detection of breast cancer Agree Disagree Neither I examine my patients' breasts annually starting at approximately age (y): 20 30 ->40 1 recommend breast self-examination starting at approximately age (y): 20 30 Other I recommend annual mammography at approximately age (y): 30 40 50 When I discover that a patient of mine is not having mammography at the recommended intervals, I do the following: Recommend it on the next visit Make an appointment for her Telephone or write to her or other Knowledge of genetic susceptibility to breast cancer Percentage of breast cancer patients having an inherited predisposition to breast cancer 3% 10%" 20% 30% 40% Type of cancer commonly associated with familial breast cancer Ovarian cancer" Lung cancer Gastric cancer Other sites Features of breast cancer associated with an inherited predisposition Earlier age of onset* Dominant inheritance pattern" Transmission of susceptibility only through females Characteristic histologic feature Multiple primary breast cancers* Occurrence in males"
63.7% 30.4% 5.9% 73.9% 20.3% 5.8% 91.3% 5.7% 3.0% 85.6% 8.7% 5.7°1o
65.3% 27.5% 7.2%
1.4%
53.6% 45.0%
44.9% 31.9% 23.2%
12.2% 34.7% 20.3% 17.2% 15.6%
78.5% 10.8% 6.2% 4.5% 75.4%* 60.9%* 78.30/0* 82.5%* 36.2%* 34.8%*
* Correct answer. , Percent answering correctly.
Obstetrics & Gynecology
Table 2. Opinions About Testing for a Genetic Susceptibility to Breast Cancer (N -- 105)
The DNA test described for detecting a genetic predisposition to breast cancer is accurate e n o u g h to be clinically useful A y o u n g w o m a n with a positive family history of breast cancer not currently having regular m a m m o g r a p h y is likely to benefit from taking the DNA test because a positive result may stimulate her to start m a m m o g r a p h y earlier A w o m a n with a positive family history of breast cancer should be referred for DNA testing even though she is already having annual m a m m o g r a p h y A w o m a n with a positive family history of breast cancer who has already had breast cancer should be referred for DNA testing A w o m a n receiving a positive DNA test result: Is likely to be excessively anxious May be discriminated against for insurance purposes Will be more likely to have a breast biopsy for a minimal m a m m o g r a p h i c abnormaIRy than if she were not DNA tested Who inquires about prophylactic mastectomy should be referred to a surgeon for consultation Should be encouraged to refer female relatives for testing Should be able to have her daughters younger than 18 tested if she desires
tures. However, only a minority (36.2%) recognized multiple primary breast cancers as a feature. Furthermore, occurrence in males is a feature of some families with an inherited susceptibility to breast cancer; affected males are more characteristic of mutations of BRCA2 than of BRCA1. s Table 2 lists the physicians' attitudes about BRCA1 testing. Most of the physicians we surveyed agreed strongly or somewhat with the statement that DNA testing today can detect a genetic predisposition to breast cancer accurately enough to be clinically useful (85 of 105, 80.9%) and that a young woman with a family history of breast cancer not currently having regular m a m m o g r a p h y is likely to benefit from taking the DNA test because a positive result may stimulate her to start m a m m o g r a p h y earlier and increase her chances of survival (87.6%). Smaller majorities agreed with the statements that a woman with a family history of breast cancer should be referred for DNA testing even though she is already having mammography (73.4%) and even if she already had breast cancer (66.7%).
Discussion The reported surveillance practices of the physicians surveyed were generally in accord with the recommendations of the American Cancer Society. 9 The divided opinion about the age for starting annual mammography between ages 40 and 50 reflects the division of VOL. 88, NO. 4 (PART 1), OCTOBER 1996
Disagree (%)
Neither agree nor disagree (%)
Agree somewhat(%)
Strongly agree (%)
6.7
12.4
47.6
33.3
7.7
4.7
37.1
50.5
6.7
19.9
32.4
41.0
14.3
19.0
28.6
38.1
7.7 7.6 4.8
5.6 17.2 10.4
43.8 47.6 32.4
42.9 27.6 52.4
6.7
20.0
39,0
34.3
3.9 32.3
6.6 21.9
23.8 22.0
65.7 23.8
opinion between the American Cancer Society9 and the National Institutes of Health. ~° Of course, responses to a survey may reflect what physicians understand should be their behavior rather than their actual behavior. A large majority (91 of 105, 86.7%) of respondents thought that women testing positive are likely to be excessively anxious (Table 2). Concern about the response to a positive test result is warranted. Some individuals who consent to genetic testing expect a reassuring result and are unprepared for an abnormal result. To assess interest in a test to detect a genetic susceptibility to breast cancer, we conducted a survey of Rochester women waiting to see their obstetriciangynecologist or to have a mammogram. We found that 44% would be very anxious about developing breast cancer if such a test were positive, jl A survey of women with a family history of breast cancer by Lerman et al j2 suggested that those likely to accept such a test might be the most prone to excessive worry after a positive result. At present, there is no strategy that can guarantee the survival of such women. Therefore, it will be the responsibility of the individual offering the test to adequately educate the patient about the benefits and burdens of BRCA1 testing so that each woman can decide for herself whether the benefits of testing outweigh the burdens. Clinical trials of BRCA1 mutation screening, now under way, can be expected to produce guidelines for the primary care physician in this regard. In the meantime, useful suggestions for the primary R o w l e y a n d Loader
Breast Cancer Genetic Testing
613
care provider about such pre-test and post-test counseling have been published recently. 13 Many respondents (75.2%) thought that w o m e n testing positive might be discriminated against for insurance purposes (Table 2). The Americans for Disabilities Act has been interpreted as prohibiting an employer from an adverse e m p l o y m e n t decision on the basis of an individual's genetic predisposition to disease. 14 Federal legislation has been proposed that would protect individual privacy while permitting genetic analysis for medical and identification purposes and legitimate research. ~4 However, the degree of protection offered must be tested in court, ~5 and litigation itself might require the type of disclosure that the patient wants to avoid. The possibility of discrimination, especially for medical insurance purposes, is one of the risks about which the test offerer must inform the patient before collecting a sample. Most respondents (84.8%) believed that a w o m a n receiving a positive DNA test result is more likely to have a breast biopsy for a minimal m a m m o g r a p h i c abnormality than if she were not DNA-tested. A lower threshold for biopsy in such w o m e n m a y be appropriate. The majority (73.3%) believed that a w o m a n receiving a positive DNA test result who inquires about prophylactic mastectomy should be referred to a surgeon for consultation. However, w o m e n who have had prophylactic surgery can still develop breast cancer since some breast tissue is inevitably left behind. The person offering the test has a responsibility for providing not only education before testing, but counseling after testing. It must be explained that the detection of a BRCA1 mutation does not make developing breast cancer a certainty, just as the absence of a mutation does not eliminate the baseline risk possessed by any w o m a n without a family history of the disease. A large majority believed that a w o m a n receiving a positive D N A test result should be encouraged to refer female relatives for testing (89.5%). This is an important finding because each first-degree relative of such a patient has a 50% chance of also having the mutation, whereas an unrelated person has only about a 0.5% chance. Hence, screening relatives of persons with mutations is m u c h more efficient than screening the general population. Opinion was divided about the appropriateness of offering the testing of any daughters u n d e r 18 to a w o m a n found to have a BRCA1 mutation. A recent statement 16 by the American Society of H u m a n Genetics discourages genetic testing of children of any kind unless intervention is indicated in childhood; the rationale is that it is preferable for each individual to m a k e her o w n decision about D N A testing and that parental anxiety should not override this consideration. O u r p u r p o s e was to assess physician attitudes, not
614
Rowley and Loader
BreastCancer Genetic Testing
the educational effectiveness of our presentation. Because the respondents had limited information about BRCA1 before our presentation, it was necessary to give them background information before assessing their attitudes. Although we tried to be objective and unbiased in our presentation of the facts, it is possible that an equally evenhanded, but different, presentation of these facts might have resulted in a different distribution of attitudes. Also, we did not assess how representative Rochester obstetrician-gynecologists are of obstetrician-gynecologists nationally. The physicians' opinion that BRCA1 testing might have value was supported by their responses to an invitation to participate in the clinical trial. Of the 105 obstetrician-gynecologists attending any of these meetings, 74 (70%) agreed to participate and only five declined; five were undecided and 21 did not respond. Reasons for declining were lack of an intervention of proven effectiveness and concern about discrimination. Some w h o were undecided or unresponsive may have delayed to confer with practice partners. We suggest two reasons for the willingness of the o v e r w h e l m i n g majority of the respondents to participate in this clinical trial. One reason is their perception of their patients' eagerness for more information about their personal risk for developing breast cancer and their patients' hope that more information will, in some undefined way, yield greater personal protection. A second reason is the recognition that w o m e n are likely to differ in their desire for and response to testing and that only careful clinical trials can provide a solid basis for guiding physicians in this uncharted area.
References 1. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990;250:1684-9. 2. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCAI. Science 1994;266:66-71. 3. Shattuck-Eidens D, McClure M, Simard J, Labrie F, Narod S, Couch F, et al. A collaborativesurvey of 80 mutations in the BRCA1breast and ovarian cancer su~eptibility gene. JAMA 1995;273:535-41. 4. Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families. Am J Hum Genet 1993;52:678-701. 5. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCAl and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995;57:1457-62. 6. Lane DS, Burg MA. Breast cancer screening. Changing physician practices and specialty,variation. N Y State J Med 1990;90:288-92. 7. King M-C, Rowell S, LoveSM. Inherited breast and ovarian cancer. What are the risks? What are the choices?]AMA 1993;269:1975-80. 8. Stratton MR, Ford D, Neuhasen S, Seal S, Wooster R, Friedman LS, et al. Familial male breast cancer is not linked to the BRCAI locus on chromosome 17q. Nat Genet 1994;7:103-7.
Obstetrics & Gynecology
9. Cancer facts and figures: 1995. Atlanta, Georgia: American Cancer Society, 1995. 10. National Cancer Institute. Working guidelines for early detection: Rationale and supporting evidence to decrease mortality. Bethesda, Maryland: National Cancer Institute, 1987. 11. Chaliki H, Loader S, Levenkron JC, Logan-Young W, Hall WJ, Rowley PT. Women's receptivity to testing for a genetic susceptibility to breast cancer. Am J Publ Health 1995;85:1133--5. 12. Lerman C, Daly M, Masny A, Balsham A. Attitudes about genetic testing for breast-ovarian cancer susceptibility. J Clin Oncol 1994; 12:843-50. 13. Hoskins KF, Stopfer JE, Calzone KA, Merajver SD, Rebbeck TR, Garber JE, et al. Assessment and counseling for women with a hmily history of breast cancer. JAMA 1995;273:577-85. 14. Hudson KL, Rothenberg KG, Andrews LB, Kahn MIE, Collins PS, Brody LC. Genetic discrimination and health insurance: An urgent need for reform. Science 1995;270:391-3. 15. The Ad Hoc Committee on Genetic Testing/Insurance Issues. Background statement: Genetic testing and insurance. Am J Hum Genet 1995;56:327-31. 16. The American Society of Human Genetics Board of Directors and the American College of Medical Genetics Board of Directors.
Points to consider:. Ethical, legal and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet 1995;57:1233-41.
Address reprint requests to: Peter T. Rowhw, MD Division of Genetics, Box 641 University of Rochester School of Medicine 601 Elmwood Aoenue Rochester, NY 14642
Received Februa~. 9, 1996. Received in revised form April 19, 1996. Accepted May 21, 1996.
Copyright © 1996 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
A D V A N C E D OPERATIVE LAPAROSCOPY AND HYSTEROSCOPY
December 5-7, 1996 The American College of Obstetricians and Gynecologists is sponsoring a course on laparoscopy and hysteroscopy, to be held at the Birmingham Medical Forum and Sheraton Civic Center Hotel, in Birmingham, Alabama. This course has been approved for 23 cognate hours (Formal Learning) by The American College of Obstetricians and Gynecologists. For further information, contact the Registrar, The American College of Obstetricians and Gynecologists, 409 12th Street SW, Washington, DC 20024-2188; (202) 863-2541.
VOL. 88, NO. 4 (PART l), OCTOBER 1996
R o w l e y a n d Loader
Breast Cancer Genetic Testing
615
In 1990, a genetic locus for breast cancer susceptibility, BRCA1, was identified on the long arm of chromosome 17.1 In 1994, the cloning of the BRCA1 gene was reported. 2 The gene was identified by the finding that it was mutated in the affected members of families with breast and ovarian cancer, but not in unaffected individuals. Until March 1996, at least 100 different mutations in affected families have been found. 3 Individuals with a BRCA1 mutation have an 82% risk of developing breast cancer by age 70 and often have an earlier age of onset than individuals from breast-cancer families with-
From the Department of Medicine and the Division of Genetics, University of Rochester School of Medicine, Rochester. New York.
VOL. 88, NO. 4 (PART 1), OCTOBER 1996
out a BRCAI mutation. 4 It has been estimated indirectly that one in 833 w o m e n have a BRCA1 mutation, s We are planning to conduct a pilot study of DNA screening for BRCA1 mutations to determine whether or not w o m e n with a positive family history benefit. This study will involve 1) identifying w o m e n with a positive family history of breast cancer, 2) offering BRCA1 testing, 3) explaining the result, and 4) assessing its impact, both its positive effects (increased understanding, adoption of early detection measures, or reassurance) and its potential negative effects (anxiety, stigmatization, and discrimination as partner, insuree, or employee). To ensure that our trial would identify outcomes likely to occur when such testing is adopted as a service, rather than as a research effort, we wished to have w o m e n learn about the program through their own physicians. Obstetrician-gynecologists are more likely to refer w o m e n for m a m m o g r a p h y than are internists. 6 Hence, the first step was to assess the attitudes of area obstetrician-gynecologists to such testing. We here rep o r t the attitudes of the s u r v e y e d obstetriciangynecologists toward DNA testing for a genetic susceptibility to breast cancer.
Materials and Methods Between October 1994 and February 1995, presentations were m a d e at the regular staff conferences of all five Rochester hospitals having obstetric services. At the beginning of each conference, a questionnaire was a d m i n i s t e r e d to assess the staff's current breastscreening practices and their knowledge of inherited predisposition to breast cancer. Next, a 30- to 40-minute explanation was given of the magnitude of the breast-cancer problem, the clinical characteristics of the familial form, the relevant facts about BRCA1, and the design of the proposed clinical
0029-7844/96/$15.00 611 PII S0029-7844(96)00199-8
trial. It w a s a d m i t t e d that only 30-50% of families with multiple cases of breast cancer h a v e m u t a t i o n s in BRCA1, s that there is no clinically available test to identify the responsible m u t a t i o n in m o s t of the remaining families, and that there is no intervention to recomm e n d to those f o u n d to have a BRCA1 m u t a t i o n that will eliminate the risk of d y i n g from breast or ovarian cancer. Questions about the material presented were answered. Finally, a second questionnaire w a s administered to the physicians to assess attitudes t o w a r d BRCA1 testing to determine w h e t h e r they w i s h e d to participate in this clinical trial. Of the 124 area prenatal care providers, a total of 69 were present at the beginning of one of the conferences and completed the k n o w l e d g e questionnaire, and 105 were present for the presentation itself and completed the attitude questionnaire at the end of one of the conferences. This project was a p p r o v e d by the University of Rochester Research Subjects Review Board.
Results The physicians' responses regarding early detection of breast cancer are s h o w n in Table 1. The p r o p o r t i o n agreeing strongly or agreeing s o m e w h a t with the statem e n t that physician breast examination is an effective m e a n s for the early detection of breast cancer was 44 of 69 or 71%. The s a m e belief a b o u t breast self-examination w a s held by 73.9%, w h e r e a s the same belief about annual m a m m o g r a p h y was held by a larger percentage, 91.3%. Most physicians r e c o m m e n d e d annual physician examination beginning at age 20 (85.6%) and regular self-examination starting either at age 20 (65.3%) or age 30 (27.5%), but they were d i v i d e d a b o u t the age for starting annual m a m m o g r a p h y b e t w e e n ages 40 (53.6%) and 50 (45%). Thus, in terms of effectiveness as a m e a n s for the early detection of breast cancer, r e s p o n d e n t s r a n k e d a n n u a l m a m m o g r a p h y first, m o n t h l y selfexamination second, and annual examination by a physician third (Table 1). Despite rating m a m m o g r a p h y as m o s t effective, only 31.9% w o u l d m a k e an appointm e n t for the n o n c o m p l i a n t patient. The physicians' k n o w l e d g e of inherited predisposition to breast cancer w a s also briefly assessed. The largest n u m b e r g a v e the correct a n s w e r for the percentage of breast cancer patients w h o are believed to have an inherited predisposition thereto, ie, 10%. 7 The majority also recognized that the type of t u m o r c o m m o n l y f o u n d in families with breast cancer is ovarian cancer (78.5%). The majority correctly identified an early age of onset (52 of 69, 75.4%) and a d o m i n a n t inheritance pattern (60.9%) as characteristic features. The majority also r e c o g n i z e d that transmission t h r o u g h females only a n d characteristic histologic a p p e a r a n c e are not lea612
R o w l e y and Loader
BreastCancer Genetic Testing
Table 1. Responses Before Explanation About BRCA1
Testing (N = 69) Item
Response
Current practice regarding early detection of breast cancer Annual physician breast examination is an effective means for the early detection of breast cancer Agree Disagree Neither Monthly self-examination is an effective means for the early detection of breast cancer Agree Disagree Neither Annual mammography is an effective means for the early detection of breast cancer Agree Disagree Neither I examine my patients' breasts annually starting at approximately age (y): 20 30 ->40 1 recommend breast self-examination starting at approximately age (y): 20 30 Other I recommend annual mammography at approximately age (y): 30 40 50 When I discover that a patient of mine is not having mammography at the recommended intervals, I do the following: Recommend it on the next visit Make an appointment for her Telephone or write to her or other Knowledge of genetic susceptibility to breast cancer Percentage of breast cancer patients having an inherited predisposition to breast cancer 3% 10%" 20% 30% 40% Type of cancer commonly associated with familial breast cancer Ovarian cancer" Lung cancer Gastric cancer Other sites Features of breast cancer associated with an inherited predisposition Earlier age of onset* Dominant inheritance pattern" Transmission of susceptibility only through females Characteristic histologic feature Multiple primary breast cancers* Occurrence in males"
63.7% 30.4% 5.9% 73.9% 20.3% 5.8% 91.3% 5.7% 3.0% 85.6% 8.7% 5.7°1o
65.3% 27.5% 7.2%
1.4%
53.6% 45.0%
44.9% 31.9% 23.2%
12.2% 34.7% 20.3% 17.2% 15.6%
78.5% 10.8% 6.2% 4.5% 75.4%* 60.9%* 78.30/0* 82.5%* 36.2%* 34.8%*
* Correct answer. , Percent answering correctly.
Obstetrics & Gynecology
Table 2. Opinions About Testing for a Genetic Susceptibility to Breast Cancer (N -- 105)
The DNA test described for detecting a genetic predisposition to breast cancer is accurate e n o u g h to be clinically useful A y o u n g w o m a n with a positive family history of breast cancer not currently having regular m a m m o g r a p h y is likely to benefit from taking the DNA test because a positive result may stimulate her to start m a m m o g r a p h y earlier A w o m a n with a positive family history of breast cancer should be referred for DNA testing even though she is already having annual m a m m o g r a p h y A w o m a n with a positive family history of breast cancer who has already had breast cancer should be referred for DNA testing A w o m a n receiving a positive DNA test result: Is likely to be excessively anxious May be discriminated against for insurance purposes Will be more likely to have a breast biopsy for a minimal m a m m o g r a p h i c abnormaIRy than if she were not DNA tested Who inquires about prophylactic mastectomy should be referred to a surgeon for consultation Should be encouraged to refer female relatives for testing Should be able to have her daughters younger than 18 tested if she desires
tures. However, only a minority (36.2%) recognized multiple primary breast cancers as a feature. Furthermore, occurrence in males is a feature of some families with an inherited susceptibility to breast cancer; affected males are more characteristic of mutations of BRCA2 than of BRCA1. s Table 2 lists the physicians' attitudes about BRCA1 testing. Most of the physicians we surveyed agreed strongly or somewhat with the statement that DNA testing today can detect a genetic predisposition to breast cancer accurately enough to be clinically useful (85 of 105, 80.9%) and that a young woman with a family history of breast cancer not currently having regular m a m m o g r a p h y is likely to benefit from taking the DNA test because a positive result may stimulate her to start m a m m o g r a p h y earlier and increase her chances of survival (87.6%). Smaller majorities agreed with the statements that a woman with a family history of breast cancer should be referred for DNA testing even though she is already having mammography (73.4%) and even if she already had breast cancer (66.7%).
Discussion The reported surveillance practices of the physicians surveyed were generally in accord with the recommendations of the American Cancer Society. 9 The divided opinion about the age for starting annual mammography between ages 40 and 50 reflects the division of VOL. 88, NO. 4 (PART 1), OCTOBER 1996
Disagree (%)
Neither agree nor disagree (%)
Agree somewhat(%)
Strongly agree (%)
6.7
12.4
47.6
33.3
7.7
4.7
37.1
50.5
6.7
19.9
32.4
41.0
14.3
19.0
28.6
38.1
7.7 7.6 4.8
5.6 17.2 10.4
43.8 47.6 32.4
42.9 27.6 52.4
6.7
20.0
39,0
34.3
3.9 32.3
6.6 21.9
23.8 22.0
65.7 23.8
opinion between the American Cancer Society9 and the National Institutes of Health. ~° Of course, responses to a survey may reflect what physicians understand should be their behavior rather than their actual behavior. A large majority (91 of 105, 86.7%) of respondents thought that women testing positive are likely to be excessively anxious (Table 2). Concern about the response to a positive test result is warranted. Some individuals who consent to genetic testing expect a reassuring result and are unprepared for an abnormal result. To assess interest in a test to detect a genetic susceptibility to breast cancer, we conducted a survey of Rochester women waiting to see their obstetriciangynecologist or to have a mammogram. We found that 44% would be very anxious about developing breast cancer if such a test were positive, jl A survey of women with a family history of breast cancer by Lerman et al j2 suggested that those likely to accept such a test might be the most prone to excessive worry after a positive result. At present, there is no strategy that can guarantee the survival of such women. Therefore, it will be the responsibility of the individual offering the test to adequately educate the patient about the benefits and burdens of BRCA1 testing so that each woman can decide for herself whether the benefits of testing outweigh the burdens. Clinical trials of BRCA1 mutation screening, now under way, can be expected to produce guidelines for the primary care physician in this regard. In the meantime, useful suggestions for the primary R o w l e y a n d Loader
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care provider about such pre-test and post-test counseling have been published recently. 13 Many respondents (75.2%) thought that w o m e n testing positive might be discriminated against for insurance purposes (Table 2). The Americans for Disabilities Act has been interpreted as prohibiting an employer from an adverse e m p l o y m e n t decision on the basis of an individual's genetic predisposition to disease. 14 Federal legislation has been proposed that would protect individual privacy while permitting genetic analysis for medical and identification purposes and legitimate research. ~4 However, the degree of protection offered must be tested in court, ~5 and litigation itself might require the type of disclosure that the patient wants to avoid. The possibility of discrimination, especially for medical insurance purposes, is one of the risks about which the test offerer must inform the patient before collecting a sample. Most respondents (84.8%) believed that a w o m a n receiving a positive DNA test result is more likely to have a breast biopsy for a minimal m a m m o g r a p h i c abnormality than if she were not DNA-tested. A lower threshold for biopsy in such w o m e n m a y be appropriate. The majority (73.3%) believed that a w o m a n receiving a positive DNA test result who inquires about prophylactic mastectomy should be referred to a surgeon for consultation. However, w o m e n who have had prophylactic surgery can still develop breast cancer since some breast tissue is inevitably left behind. The person offering the test has a responsibility for providing not only education before testing, but counseling after testing. It must be explained that the detection of a BRCA1 mutation does not make developing breast cancer a certainty, just as the absence of a mutation does not eliminate the baseline risk possessed by any w o m a n without a family history of the disease. A large majority believed that a w o m a n receiving a positive D N A test result should be encouraged to refer female relatives for testing (89.5%). This is an important finding because each first-degree relative of such a patient has a 50% chance of also having the mutation, whereas an unrelated person has only about a 0.5% chance. Hence, screening relatives of persons with mutations is m u c h more efficient than screening the general population. Opinion was divided about the appropriateness of offering the testing of any daughters u n d e r 18 to a w o m a n found to have a BRCA1 mutation. A recent statement 16 by the American Society of H u m a n Genetics discourages genetic testing of children of any kind unless intervention is indicated in childhood; the rationale is that it is preferable for each individual to m a k e her o w n decision about D N A testing and that parental anxiety should not override this consideration. O u r p u r p o s e was to assess physician attitudes, not
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the educational effectiveness of our presentation. Because the respondents had limited information about BRCA1 before our presentation, it was necessary to give them background information before assessing their attitudes. Although we tried to be objective and unbiased in our presentation of the facts, it is possible that an equally evenhanded, but different, presentation of these facts might have resulted in a different distribution of attitudes. Also, we did not assess how representative Rochester obstetrician-gynecologists are of obstetrician-gynecologists nationally. The physicians' opinion that BRCA1 testing might have value was supported by their responses to an invitation to participate in the clinical trial. Of the 105 obstetrician-gynecologists attending any of these meetings, 74 (70%) agreed to participate and only five declined; five were undecided and 21 did not respond. Reasons for declining were lack of an intervention of proven effectiveness and concern about discrimination. Some w h o were undecided or unresponsive may have delayed to confer with practice partners. We suggest two reasons for the willingness of the o v e r w h e l m i n g majority of the respondents to participate in this clinical trial. One reason is their perception of their patients' eagerness for more information about their personal risk for developing breast cancer and their patients' hope that more information will, in some undefined way, yield greater personal protection. A second reason is the recognition that w o m e n are likely to differ in their desire for and response to testing and that only careful clinical trials can provide a solid basis for guiding physicians in this uncharted area.
References 1. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990;250:1684-9. 2. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCAI. Science 1994;266:66-71. 3. Shattuck-Eidens D, McClure M, Simard J, Labrie F, Narod S, Couch F, et al. A collaborativesurvey of 80 mutations in the BRCA1breast and ovarian cancer su~eptibility gene. JAMA 1995;273:535-41. 4. Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families. Am J Hum Genet 1993;52:678-701. 5. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCAl and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995;57:1457-62. 6. Lane DS, Burg MA. Breast cancer screening. Changing physician practices and specialty,variation. N Y State J Med 1990;90:288-92. 7. King M-C, Rowell S, LoveSM. Inherited breast and ovarian cancer. What are the risks? What are the choices?]AMA 1993;269:1975-80. 8. Stratton MR, Ford D, Neuhasen S, Seal S, Wooster R, Friedman LS, et al. Familial male breast cancer is not linked to the BRCAI locus on chromosome 17q. Nat Genet 1994;7:103-7.
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9. Cancer facts and figures: 1995. Atlanta, Georgia: American Cancer Society, 1995. 10. National Cancer Institute. Working guidelines for early detection: Rationale and supporting evidence to decrease mortality. Bethesda, Maryland: National Cancer Institute, 1987. 11. Chaliki H, Loader S, Levenkron JC, Logan-Young W, Hall WJ, Rowley PT. Women's receptivity to testing for a genetic susceptibility to breast cancer. Am J Publ Health 1995;85:1133--5. 12. Lerman C, Daly M, Masny A, Balsham A. Attitudes about genetic testing for breast-ovarian cancer susceptibility. J Clin Oncol 1994; 12:843-50. 13. Hoskins KF, Stopfer JE, Calzone KA, Merajver SD, Rebbeck TR, Garber JE, et al. Assessment and counseling for women with a hmily history of breast cancer. JAMA 1995;273:577-85. 14. Hudson KL, Rothenberg KG, Andrews LB, Kahn MIE, Collins PS, Brody LC. Genetic discrimination and health insurance: An urgent need for reform. Science 1995;270:391-3. 15. The Ad Hoc Committee on Genetic Testing/Insurance Issues. Background statement: Genetic testing and insurance. Am J Hum Genet 1995;56:327-31. 16. The American Society of Human Genetics Board of Directors and the American College of Medical Genetics Board of Directors.
Points to consider:. Ethical, legal and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet 1995;57:1233-41.
Address reprint requests to: Peter T. Rowhw, MD Division of Genetics, Box 641 University of Rochester School of Medicine 601 Elmwood Aoenue Rochester, NY 14642
Received Februa~. 9, 1996. Received in revised form April 19, 1996. Accepted May 21, 1996.
Copyright © 1996 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
A D V A N C E D OPERATIVE LAPAROSCOPY AND HYSTEROSCOPY
December 5-7, 1996 The American College of Obstetricians and Gynecologists is sponsoring a course on laparoscopy and hysteroscopy, to be held at the Birmingham Medical Forum and Sheraton Civic Center Hotel, in Birmingham, Alabama. This course has been approved for 23 cognate hours (Formal Learning) by The American College of Obstetricians and Gynecologists. For further information, contact the Registrar, The American College of Obstetricians and Gynecologists, 409 12th Street SW, Washington, DC 20024-2188; (202) 863-2541.
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