- Email: [email protected]
Awareness and concern about ovarian cancer among women at risk because of a family history of breast or ovarian cancer
Awareness and concern about ovarian cancer among women at risk because of a family history of breast or ovarian cancer M. Robyn Andersen, MPH, PhD,*y Deborah Bowen, PhD,*y Yutaka Yasui, PhD,*z and Anne McTiernan, MD, PhD*y Seattle, WA Research on women at risk for breast cancer because of family history suggests that a substantial proportion need education and counseling to assist them in their efforts to understand their risk of breast cancer and that some do not get appropriate breast cancer screening. Although women at high genetic risk for breast cancer are at elevated risk for ovarian cancer as well, few studies have examined these women’s needs for education and counseling about ovarian cancer risk. This study examined awareness of ovarian cancer, perceived risk of breast and ovarian cancer, interest in genetic testing, and use of screening for breast and ovarian cancer in a population-based sample of women at high risk for breast and ovarian cancer because of a strong family history of cancer at one or both sites. We found that most high-risk women are not getting the information and care they need with respect to their risk for ovarian cancer. Almost 75% have not heard much about their risk for ovarian cancer. More than 90% failed to use 1 or another of 2 possible tests used for ovarian cancer screening regularly. (Am J Obstet Gynecol 2003;189:S42-S47.)
Key words: Genetics, ovarian cancer, risk, screening
Research on women at high-risk for breast cancer because of family history suggests that a substantial proportion need education and counseling to assist them in their efforts to understand their risk of breast cancer and to get appropriate breast cancer screening. These women have been found to have unrealistic beliefs about their risk for breast cancer, and to report high levels of worry about their risk.1,2 However, breast cancer is not the only cancer risk that these women might face. A family history of breast and/or ovarian cancer among close family relatives (mother, sisters, daughters) may indicate a woman is at increased risk for carrying a mutation in either BRCA1 or BRCA2.3,4 Such a mutation confers a considerably higher than average risk of both breast and ovarian cancer. Although the average woman’s lifetime risk for ovarian cancer is 1.8% and her risk for breast cancer is approximately 11%.5 Estimates of risk of ovarian cancer for mutation carriers are thought to be between 16% and 45% lifetime risk,6-8 whereas the risk of breast cancer is thought to be between 56% and 85%.9-12 Although BRCA1 and BRCA2 mutations are associated with both breast and ovarian cancer and this means women at high-risk for breast cancer because of a possible mutation are also at risk for ovarian cancer, few studies From the *Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center; the yDepartment of Health Services, and the zDepartment of Biostatistics, University of Washington, Seattle, WA. Address reprint requests to M. Robyn Andersen, Fred Hutchinson Cancer Research Center, 1100 Fainnew Ave. N. MP-900, P.O. Box 19024, Seattle, WA 98109-1024. Ó 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/S0002-9378(03)01078-0
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have examined high-risk women’s beliefs about their ovarian cancer risk and need for education and counseling regarding their risk for ovarian cancer. Risk for being a mutation carrier increases with the number and age of affected relatives. Studies examining issues for high-risk women have defined risk in several different ways. For this study we defined high-risk as persons with multiple first- or second-degree family members with breast or ovarian cancer or a first-degree relative who was affected before age 60. As they do with breast cancer, high-risk women have important decisions to make regarding what to do to reduce their risk of getting and/or dying of ovarian cancer. These women may chose to have genetic testing performed to help clarify their risk of cancer, but this does not directly reduce their risk of either cancer.4,13 Prophylactic surgery is an option as it reduces the risk of ovarian cancer, but unfortunately, it does not eliminate it entirely.14 Screening is also an option. Although ovarian cancer screening is not recommended for average risk women, there are two methods of screening for ovarian cancer currently under investigation.15-17 The first uses measures of serum CA-12517-19 whereas the second method uses ultrasound to visualize the ovaries.16,20 The effectiveness of either of these tests as a method of screening women for ovarian cancer is still being examined in clinical trials.21 It has, however, been recommended for women who are at high-risk and have multiple affected relatives because of the possibility that these women may be mutation carriers.22 In summary, women with a high-risk family history of breast and/or ovarian cancer are at higher than average
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risk for both diseases and have important decisions to make about options for reducing their risk for ovarian cancer and/or their risk of dying of it. It is therefore important to assess their awareness of their risk for ovarian cancer, their beliefs about their risk for ovarian cancer, and about their use of ovarian cancer screening. This study sought to examine a population-based sample of high-risk women, women’s perceptions of their risk for ovarian cancer and their interest in and use of genetic testing, breast, and ovarian cancer screening. We hypothesized that high-risk women, especially those without a relative affected by ovarian cancer, may not have good knowledge of their ovarian cancer risk and fail to use currently available tests for ovarian cancer screening. Materials and methods Participant recruitment and survey. Participants for this study were recruited for an intervention study of provision of breast cancer risk education. All study procedures were reviewed and approved by the Human Subjects Internal Review Board of the Fred Hutchinson Cancer Research Center, and conformed with the ethical guidelines of the 1975 Declaration of Helsinki. We purchased a list of names and contact data from Mailing Lists Plus, a local research survey and list company. This company uses publicly available lists, including Department of Licensing lists and voter registration lists, matched with commercial and other information to obtain up-to-date contact information for adult populations. The company estimates that they consistently obtain 80% of the adult population in their lists, compared with census data. The requirements for the list were women, aged 18 to 74, with contact information in a geographically defined area in King County, WA. We mailed initial informed consent letters to a random sample of residents, requesting them to contact us if they did not want to receive a survey call. We telephoned potential participants, collected basic eligibility information (age as above, English-speaking, no previous diagnosis of cancer, intent to live in their residence for 1 year, and willingness to complete questionnaires), described the study, and invited participation. If the potential participant agreed to participate in the study and consented to participate in all study procedures, she was asked to complete the baseline survey. We completed 2,123 survey calls, and of the 1,934 eligible individuals, we completed 1,366 baseline surveys. We used the methods recommended by a leading survey research group (http://www.aapor.org, method #4) to calculate response rate. This calculation is the number of completed contacts over the number of contacts plus the number of eligible refusals and noncontacts, and an estimated proportion of the potential contacts that were eligible. Using this procedure, we calculated a 72% response rate for this survey.
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The baseline telephone surveys were completed by women talking with trained and monitored interviewers. The interview lasted about 45 minutes, and included measures of family history, presence of breasts and ovaries, awareness of breast and ovarian cancer, perceived risk of breast and ovarian cancer, worry about breast and ovarian cancer risk, awareness of and view about genetic testing, screening intentions and behaviors, and demographics. Survey measures. Demographic variables assessed included age, race, income, education, marital status, employment status, and health care coverage measures of demographics consisted of simple single items used in our previous research projects. Information on women’s personal history of breast or ovarian cancer and the presence of breasts and ovaries was used to determine both a woman’s likely risk of developing breast or ovarian cancer and her suitability for various cancer screening activities. For these analyses women without breasts or ovaries because of prophylactic surgery were excluded from the dataset. Family history information was provided by women in response to the question ‘‘Has (name of relation; eg, your mother) ever had cancer?’’ If yes, further data were collected on the type of cancer and patient’s age at diagnosis. This allowed for the classification of women as high-risk for a mutation associated with increased risk for breast or ovarian cancer or as at genetically low risk (and thus at approximately average risk for these diseases overall). Women were considered high-risk if they reported at least 1 first-degree relative (eg, a mother, sister, or daughter) affected by breast cancer before the age of 60, or 2 first-degree relatives with breast or ovarian cancer at any age. Women were also considered high-risk if they reported 2 first- or second-degree relatives (eg, aunts, grandparents, half sisters) with breast or ovarian cancer on the same side of the family, or 1 first-degree male relative (eg, father, brother or son) with breast cancer (Table I). Although we did not assess women’s knowledge about cancer at each site women were asked about their awareness of each cancer via questions asking how much they had read or heard about each cancer. Response categories for these questions include ‘‘very little,’’ ‘‘some,’’ ‘‘a fair bit,’’ and ‘‘a lot.’’ Use of genetic testing was assessed by asking women if they’d ever had genetic testing of any sort, and then asking them to specify what kind of genetic testing they received. Responses that indicated testing for breast or ovarian cancer risk, BRCA1 or BRCA2 testing, or responses indicating cancer risk without specifying the test or organ site specifically were assumed to be BRCA1/2 testing for genetic risk for breast/ovarian cancer. Awareness of and interest in genetic testing, were assessed by asking women a series of questions. To assess awareness we asked women
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Table I. Criteria for high-risk designation One first degree relative with breast cancer before 60, or Two first degree relatives with breast or ovarian cancer at any age, or Two second degree relatives with breast or ovarian cancer on same side of the family, or One first degree relative with breast or ovarian cancer and one second degree relative with breast or ovarian cancer on same side of the family, or One first degree male relative with breast cancer
‘‘How much have you read or heard about genetic testing for cancer risk?’’ with response categories ‘‘very little,’’ ‘‘some,’’ ‘‘a fair bit,’’ and ‘‘a lot.’’ Women indicated their interest in getting genetic testing using response categories ‘‘definitely not,’’ ‘‘probably not,’’ ‘‘probably yes,’’ and ‘‘definitely yes.’’ Women’s perceptions of their risk of breast and ovarian cancer, were assessed via 2 items. The breast cancer item asked ‘‘What do you think the chances are that you will have breast cancer someday?’’. The ovarian cancer item was the same except for the organ site of the cancer named. Response categories for these items included ‘‘100%,’’ ‘‘80% to 90%,’’ ‘‘60% to 70%,’’ ‘‘about 50%,’’ ‘‘30% to 40%,’’ ‘‘20% to 30%,’’ ‘‘about 10%,’’ ‘‘about 5%,’’ ‘‘about 1%,’’ and ‘‘0%.’’ For analysis several of these categories were combined. Specifically, all the categories from ‘‘100%’’ to ‘‘about 50%’’ were combined to create a ‘‘50%+’’ category. Women’s use of cancer screening was assessed using a series of questions asking about each of the various forms of screening available. Women were asked whether they have ever had an ultrasound examination of their ovaries to screen for ovarian cancer and if so how often they have had such examinations, whether they have ever had a CA-125 blood test to look for ovarian cancer and if so how often they have had such tests. Although all women in the dataset had breast and ovaries and would thus were at least potentially candidates for cancer screening at both sites, some were not at elevated risk and under the age of 40. Therefore, women were given an option of indicating not only that they were not getting screening but that they believed each of the screening tests were not applicable for them. Results Participating women were generally white (86%), and fairly well educated (85% had completed some college or technical school training after high school; less than 2% had not completed high school). Most reported a moderate income (median household income $30,000 to $49,000), 46% were married or living with a partner, and 66% were employed outside the home. These characteristics are consistent with those of the population from which they were recruited.
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Table II. Characteristics of study sample Demographic Information Age Less than 40 40-50 50+ Race White Other Education Less than high school High school graduate College or technical school training Income Less than $15,000 $15,000 to $29,999 $30,000 to $49,999 $50,000 to $69,999 $70,000 or over Marital status Legally married Living with a partner Not living with a Partner Other Employment Full-time employed Part-time employed Not employed Retired
Average Risk
High Risk
P value
29.78% 31.20% 39.02%
25.00% 32.32% 42.68%
= .43
86.58% 13.42%
84.76% 15.24%
=.52
1.91% 13.39% 84.69%
1.22% 15.85% 82.93%
=.59
6.30% 18.99% 30.36% 19.42% 24.93%
8.07% 15.53% 31.68% 21.74% 22.98%
=.69
31.75% 14.45% 53.38%
30.49% 13.41% 54.88%
0.42%
1.22%
=.56
65.89% 12.34% 10.59% 11.18%
66.46% 9.15% 12.80% 11.59%
=.59
Among the 1,366 women participating in the project 1,202 (88%) were of approximately average risk, and 164 (12%) were considered high risk according to the study criteria. Of these ‘‘high-risk’’ women all but 5 had first or second degree relatives with breast cancer. The remaining 5 reported at least 1 first degree relative with ovarian cancer. In total 16 of the high-risk women reported at least 1 first- or second-degree relative affected by ovarian cancer. The demographic characteristics of high-risk women did not differ from those of approximately average risk in age, race, education, income, marital status or employment (P > .05 for all comparisons). See Table II for additional information. Most (75.6%) of the high-risk women reported having read or heard ‘‘a fair bit’’ or ‘‘a lot’’ about breast cancer. Self-reported levels of awareness of ovarian cancer were, however, considerably lower with only 24.4% of high-risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about ovarian cancer. Less than half (38.4%) of the high-risk women in this sample reported being definitely interested in genetic testing. In addition, levels of awareness of genetic testing were fairly low with only 23.5% of high-risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about genetic testing for cancer risk. The majority of high-risk women also reported perceived risks of breast and ovarian cancer that were unrealistically high. Of these women, 90.7% reported perceived lifetime risks of breast cancer greater than 20%,
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Table III. Awareness and perceived risks of high-risk women
Table IV. Use of genetic testing and cancer screening among women older than 50 according to risk status
High Risk
Average Risk
Statistical Significance (P)
3 (4.5%) 67 (94.5%)
21 (4.5%) 446 (94.5%)
= .94
68 (97.1%) 2 (2.9%)
457 (97.4%) 12 (2.6%)
= .88
4 (6.0%) 63 (94.0%)
32 (6.9%) 435 (93.1%)
= .53
9 (10.8%) 74 (89.2%)
61 (13.4%) 395 (86.6%)
= .79
High Risk How much have you read or heard about breast cancer? Very little Some A fair bit A lot How much have you read or heard about ovarian cancer? Very little Some A fair bit A lot How much have you read or heard about genetic testing for cancer risk? Very little Some A fair bit A lot Perceived risk of breast cancer: Less than 20% 20-50 50+ Perceived risk of ovarian cancer: Less than 20% 20-50 50+ Interest in genetic testing: Definitely not Probably not Probably yes Definitely yes
Risk Status 4.88% 19.51% 35.98% 39.63% 35.98% 39.63% 14.63% 9.76% 34.36% 41.10% 21.47% 3.07% 9.30% 58.60% 32.10% 36.06% 57.14% 6.80% 3.05% 12.80% 45.73% 38.41%
and approximately one-third (32.1%) reported perceived risks of breast cancer greater than 50%. About one-third (36.0%) of these women reported perceived risks of ovarian cancer less than 20% and 6.8% reported perceived risks of ovarian cancer greater than 50%. Characteristics of high risk women are also shown in Table III. Although average risk women tended to report similar levels of perceived risk for both cancers, only 21.9% of the participating high-risk women reported similar levels of perceived risks for the 2 cancers. The high-risk women appeared to know that their risk for ovarian cancer is much lower than their risk for developing breast cancer. Seventy three percent of the high-risk women reported perceived risks for breast cancer higher than their perceived risk for ovarian cancer. The kind of cancer reported by a woman as part of her family history appears to predict differences in levels of perceived risk of breast cancer. Among the high-risk women with a family history including at least 1 relative with breast cancer (n = 155) 75.5% reported higher levels of perceived risk for breast cancer than they did for ovarian cancer. Among the 5 women with family histories including only ovarian cancer; 3 reported perceived risks
Genetic testing Yes No Mammography use Yes No CA-125 blood test Yes No Ultrasound use Yes No
of ovarian cancer greater than those of breast cancer and 2 reported the same level of perceived risk for both cancers. Overall, use of genetic testing to clarify risk was small: only 4.5% (n = 3) of the high-risk women reported having received genetic testing. Twenty-one (also 4.5%) of those who were not at high-risk also reported having received genetic testing. The high-risk women did report use of mammography with 50% of the high-risk women reporting regular use of mammography for breast cancer screening every year. Almost all (97.1%) of the 70 high-risk women over age 50 reported recent mammography use within the past 2 years. A similar percentage (97.4%) of the women over 50 who were not high risk (n = 469), however, also reported recent mammography use. Rates of reported use of ultrasound and CA-125 blood tests for ovarian cancer screening were lower (less than 3% of the women in the high-risk group reported using either test regularly once a year). When the sample was limited to women over the age of 50; 6.0% of high-risk women and 6.9% of those who were not high risk reported use of CA-125 testing, while 10.8% of the high-risk and 13.4% of those who were not high-risk reported use of ultrasound for ovarian cancer screening. These percentages are not statistically significantly different. Table IV shows use of genetic testing and cancer screening by high and average risk women over 50 years of age. Discussion Women with high-risk family histories generally reported having read or heard ‘‘a fair bit’’ or ‘‘a lot’’ about breast cancer, despite this their knowledge about their risk for the disease was poor and these women reported unrealistically high levels of perceived risk. Women at genetic risk for breast cancer are also at high-risk for ovarian cancer. Despite this, self-reported levels of awareness of ovarian cancer were very low. Less than 30% of high-risk women reporting having heard ‘‘a fair
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bit’’ or ‘‘a lot’’ about ovarian cancer. Despite, or perhaps because of, their lack of knowledge most high-risk women also overestimate their risk for ovarian cancer. As has been reported in prior studies,23 high-risk women report considerable interest in genetic testing. In this study we found 38.4% of high-risk women reported being interested in testing. Levels of awareness of genetic testing, were, however, low with less than 25% of high risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about genetic testing for cancer risk. This suggests that in spite of interest and media coverage of issues related to BRCA1 and BRCA2 testing many high-risk women are not sufficiently well informed about testing to make informed decisions about their use of this technology. Few, (4.5%) of the high-risk women in this population sample reported having received a genetic test for cancer. This percentage was identical to the percentage of women who were not high-risk (4.5%). That similar percentages of high- and average-risk women have received genetic testing for cancer suggests potential problems in the health care system as genetic testing is really most appropriate for women who come from families with multiple affected relatives. Fortunately, women do appear have some awareness of the value of mammography as a means of screening for breast cancer 97% of high-risk women (over the age of 50) reported regular use of mammography for breast cancer screening. Unfortunately, very few of the high-risk women under the age of 50 reported screening use although such screening would generally be recommended for them. Rates of mammography use among high-risk women were not higher than rates of use by women of average risk. This finding is not unique. Although some studies have found women with a family history of breast cancer use mammography more than those without a family history24,25 studies focusing on higher risk women have not always found this to be the case.24,26,27,28 Overall, when higher levels of use have been found differences in use between high- and average-risk women have been small to moderate.24,25 This pattern of findings suggests that although high-risk women report high levels of awareness regarding breast cancer and overestimate their risk, family history associated high-risk status does not of itself spur women to get additional screening or screening at younger ages as has been recommended for women at high-risk. Physicians may need to ask women about their family history and encourage use among those they find to be at high risk if they wish to see their high-risk patients getting early or intensive screening such as is sometimes recommended for these women. Ovarian cancer screening is even more seriously underused. Although ovarian cancer screening is not recommended for average risk woman because of lack of evidence for it’s effectiveness, high-risk women who may have a genetic mutation are at elevated risk for ovarian
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cancer ovarian cancer screening is recommended for these women.22 Rates of reported use of ultrasound and CA-125 blood tests for ovarian cancer screening were less than 5% in the sample overall and only 6% (CA-125) and 11% (ultrasound) for high-risk women over 50. Although our definition of high-risk was lenient in this study and not all the women categorized as high-risk here would be good candidates for ovarian cancer screening, these rates of use are low. These findings and those of other population-based studies of high risk women29 suggest that outside of high-risk screening programs high-risk women are not be getting the screening services recommended for them. There are limitations to the study methods which must be considered when drawing conclusions from the data. First, this study was conducted in an urban/suburban area in a single region of the country where the population is generally well educated and predominantly white. There are regional variations in health care delivery and these could limit the generalizability of the results to women living in rural areas and other regions of the country. As less educated, and minority women and those living in rural areas are frequently medically under-served the results of this study probably understate the problem of lack of information and failure to use screening likely found among high-risk women nationwide. In addition, our response rate was 72%; although this is commonly considered reasonable, the results to do not include responses from approximately 28% of eligible women. These women may share characteristics that caused them to choose not to participate in research of this type. We are hopeful that this is not the case however, as the demographic data from this sample when compared with census derived data for the catchment area indicated that the sample is likely representative. An additional limitation arises from the fact that mammography and other screening service use was assessed in this study via self-report and these reports were not confirmed via contact with providers. Similarly reports of a family history of cancer were not confirmed via requests for medical records for the affected relative. Self-report data on mammography has generally been found to be quite accurate, especially reports of mammography within 1 year of an interview.30,31 The validity of self-reports of CA-125 blood tests and sonography are unknown. The accuracy of women reports of a family history of cancer has been examined and these reports have generally been found to be fairly accurate with 83% to 88% of reported cancers in first degree relatives being confirmed on request of records.32,33,34 Reports of a family history of cancer in second degree relatives have been found to be less accurate.33 It is not known how accurately people can report the age at which a relative was diagnosed with cancer. Overall, these findings suggest that high-risk women are not necessarily getting the
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information they need about their risk for breast and ovarian cancer and may benefit from genetics education interventions designed for them. Physicians should not assume that high-risk women are getting all appropriate ovarian cancer screening tests, or that if they are not, they are doing so after making an informed decision about the risks and benefits of screening considering their risk status. It is unclear why there should be so few differences in cancer screening use associated with risk status. Possibilities include failure of primary care physicians to ask about family history and to use family history information to inform patients of their risk status and direct care based on this information. Another would be failure to consider both ovarian and breast cancer together when determining risk and making recommendations for future care. In situations such as BRCA1/2 where a mutation is associated with cancer at multiple sites educational efforts may particularly important as women may not assume that a family history of cancer at one organ site puts them at risk for cancer at not only that but also another organ site. Our data suggest this is a possible issue but should be considered essentially anecdotal on this point as the number of high-risk women with affected relatives with ovarian cancer was limited and the number with family history of ovarian but not breast cancer extremely limited. REFERENCES 1. 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 Biomark Prevent 1999;8:369-75. 2. Lerman C, Schwartz M. Adherence and psychological adjustment among women at high risk for breast cancer. Breast Cancer Res Treat 1993;28:145-55. 3. Narod SA, Feunteun J, Lenoir G, et al. Familial breast- ovarian cancer locus on chromosome 17ql2-23. Lancet 1991;338:82-3. 4. American Society of Clinical Oncology. Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility. J Clin Oncol 14 1996;1730-6. 5. American Cancer Society. American Cancer Society Cancer Facts and Figures—1998. Atlanta, GA: American Cancer Society Inc, 1998. 6. Foulkes W, Glendon G, Narod S. Family history and risk of ovarian cancer. JAMA 1995;274:383. 7. Frank TS, Manley SA, Olopade OI, et al. Sequence analyses of BRCA1 and BRCA2: Correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 1998;16:2417-25. 8. Ponder BAJ, Easton DF, Peto J. Risk of ovarian cancer associated with a family history. In: Sharp F, Leake R, editors. Ovarian Cancer. London, Chapman & Hall Ltd; 1990. p. 3-6. 9. Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCAlmutation carriers. Lancet 1994;343:692-5. 10. Easton DF, Ford D, Bishop DT, et al. Breast and ovarian cancer incidence in BRCAl-mutation carriers. Am J Human Genet 1995; 56:265-71.
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11. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401-8. 12. Satagopan JM, Offit K, Foulkes W, et al. The lifetime risks of breast cancer in Ashkenazi Jewish Carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prevent 2001;10:467-73. 13. 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 1997;277:997-1003. 14. Struewing JP, Watson P, Easton DF, et al. Prophylactic oo-phorectomy in inherited breast/ovarian cancer families. J Nat Cancer Instit Mono 1995;17:33-5. 15. Carlson K, Skate S, Singer D. Screening for ovarian cancer. Ann Intern Med 1994;121:124-32. 16. Jacobs I, Davies AP, Bridges J, et al. Prevalence screening for ovarian cancer in postmenopausal women by CA125 measurement and ultrasonography. Br Med J 1993;306:1030-5. 17. Jacobs IJ, Skates S, Davies AP. Risk of diagnosis of ovarian cancer after raised serum CA-125 concentration: A prospective cohort study. Br Med J 1996;313:1355. 18. Jacobs I, Stabile I, Bridges J, et al. Multimodal approach to screening for ovarian cancer. Lancet 1988;336:268-71. 19. Bast RC Jr, Boyer CM, Xu FJ, et al. Molecular approaches to prevention and detection of epithelial ovarian cancer. J Cell Biochem 1995;23(suppl):219-22. 20. Campbell S, Bhan V, Royston P, et al. Transabdominal ultrasound screening for early ovarian cancer. Br Med J 1989;299:1363-7. 21. Rosenthal A, Jacobs I. Ovarian cancer screening. Semin On col 1998;25:315-25. 22. Ovarian cancer: Screening, treatment, and follow-up. NIH Consensus Statement Apr. 5-7 1994;12:1-30. 23. Burke W, Culver JO, Bowen D, et al. Genetic counseling for women with an intermediate family history of breast cancer. Am J Med Genet 2000;90:361-8. 24. Hailey BJ. Family history of breast cancer and screening behavior: An inverted U-shaped curve? Medical Hypoth 1991;36:397-403. 25. McCaul KD, Branstetter AD, Schroeder DM, et al. What is the relationship between breast cancer risk and mamniography screening? A meta-analytic review. Health Psychol 1996;15:423-9. 26. Vogel VG, Graves DS, Vernon SW, et al. Mammographic screening of women with increased risk of breast cancer. Cancer 1990;66:1613-20. 27. Kaplan KM, Weinberg GB, Small A, et al. Breast cancer screening among relatives of women with breast cancer. Am J Public Health 1991;81:1174-8. 28. Drossaert CC, Boer H, Seydel ER, et al. Perceived risk, anxiety, mammogram uptake, and breast self-examination of women with a family history of breast cancer: The role of knowing to be at increased risk. Cancer Detect Prevent 1996;20:76-85. 29. Dresher C, Holt SK, Andersen MR, et al. Reported ovarian cancer screening among a populations based sample in Washington State. Obstet Gynecol 2000;96:70-4. 30. King ES, Rimer BK, Trock B. How valid are mammography selfreports? Am J Public Health 1990;80:1386-8. 31. McGovern PG, Lurie N, Margolis KL, et al. Accuracy of self-report of mammography and Pap smear in a low-income urban population. Am J Prevent Med 1998;14:201-8. 32. Napier JA, Metzner H, Johnson BC. Limitations of morbidity and mortality data obtained from family histories—A report from the Tecumseh community health study. Am J Public Health 1972;62:30-5. 33. Love RR, Evans AM, Josten DM, et al. The accuracy of patient reports of a family history of cancer. J Chronic Dis 1985;38:289-93. 34. Bondy ML, Strom SS, Colopy MW, et al. Accuracy of family history of cancer obtained through interviews with relatives of patients with childhood sarcoma. J Clin Epidemiol 1994;47:89-96.
Key words: Genetics, ovarian cancer, risk, screening
Research on women at high-risk for breast cancer because of family history suggests that a substantial proportion need education and counseling to assist them in their efforts to understand their risk of breast cancer and to get appropriate breast cancer screening. These women have been found to have unrealistic beliefs about their risk for breast cancer, and to report high levels of worry about their risk.1,2 However, breast cancer is not the only cancer risk that these women might face. A family history of breast and/or ovarian cancer among close family relatives (mother, sisters, daughters) may indicate a woman is at increased risk for carrying a mutation in either BRCA1 or BRCA2.3,4 Such a mutation confers a considerably higher than average risk of both breast and ovarian cancer. Although the average woman’s lifetime risk for ovarian cancer is 1.8% and her risk for breast cancer is approximately 11%.5 Estimates of risk of ovarian cancer for mutation carriers are thought to be between 16% and 45% lifetime risk,6-8 whereas the risk of breast cancer is thought to be between 56% and 85%.9-12 Although BRCA1 and BRCA2 mutations are associated with both breast and ovarian cancer and this means women at high-risk for breast cancer because of a possible mutation are also at risk for ovarian cancer, few studies From the *Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center; the yDepartment of Health Services, and the zDepartment of Biostatistics, University of Washington, Seattle, WA. Address reprint requests to M. Robyn Andersen, Fred Hutchinson Cancer Research Center, 1100 Fainnew Ave. N. MP-900, P.O. Box 19024, Seattle, WA 98109-1024. Ó 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/S0002-9378(03)01078-0
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have examined high-risk women’s beliefs about their ovarian cancer risk and need for education and counseling regarding their risk for ovarian cancer. Risk for being a mutation carrier increases with the number and age of affected relatives. Studies examining issues for high-risk women have defined risk in several different ways. For this study we defined high-risk as persons with multiple first- or second-degree family members with breast or ovarian cancer or a first-degree relative who was affected before age 60. As they do with breast cancer, high-risk women have important decisions to make regarding what to do to reduce their risk of getting and/or dying of ovarian cancer. These women may chose to have genetic testing performed to help clarify their risk of cancer, but this does not directly reduce their risk of either cancer.4,13 Prophylactic surgery is an option as it reduces the risk of ovarian cancer, but unfortunately, it does not eliminate it entirely.14 Screening is also an option. Although ovarian cancer screening is not recommended for average risk women, there are two methods of screening for ovarian cancer currently under investigation.15-17 The first uses measures of serum CA-12517-19 whereas the second method uses ultrasound to visualize the ovaries.16,20 The effectiveness of either of these tests as a method of screening women for ovarian cancer is still being examined in clinical trials.21 It has, however, been recommended for women who are at high-risk and have multiple affected relatives because of the possibility that these women may be mutation carriers.22 In summary, women with a high-risk family history of breast and/or ovarian cancer are at higher than average
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risk for both diseases and have important decisions to make about options for reducing their risk for ovarian cancer and/or their risk of dying of it. It is therefore important to assess their awareness of their risk for ovarian cancer, their beliefs about their risk for ovarian cancer, and about their use of ovarian cancer screening. This study sought to examine a population-based sample of high-risk women, women’s perceptions of their risk for ovarian cancer and their interest in and use of genetic testing, breast, and ovarian cancer screening. We hypothesized that high-risk women, especially those without a relative affected by ovarian cancer, may not have good knowledge of their ovarian cancer risk and fail to use currently available tests for ovarian cancer screening. Materials and methods Participant recruitment and survey. Participants for this study were recruited for an intervention study of provision of breast cancer risk education. All study procedures were reviewed and approved by the Human Subjects Internal Review Board of the Fred Hutchinson Cancer Research Center, and conformed with the ethical guidelines of the 1975 Declaration of Helsinki. We purchased a list of names and contact data from Mailing Lists Plus, a local research survey and list company. This company uses publicly available lists, including Department of Licensing lists and voter registration lists, matched with commercial and other information to obtain up-to-date contact information for adult populations. The company estimates that they consistently obtain 80% of the adult population in their lists, compared with census data. The requirements for the list were women, aged 18 to 74, with contact information in a geographically defined area in King County, WA. We mailed initial informed consent letters to a random sample of residents, requesting them to contact us if they did not want to receive a survey call. We telephoned potential participants, collected basic eligibility information (age as above, English-speaking, no previous diagnosis of cancer, intent to live in their residence for 1 year, and willingness to complete questionnaires), described the study, and invited participation. If the potential participant agreed to participate in the study and consented to participate in all study procedures, she was asked to complete the baseline survey. We completed 2,123 survey calls, and of the 1,934 eligible individuals, we completed 1,366 baseline surveys. We used the methods recommended by a leading survey research group (http://www.aapor.org, method #4) to calculate response rate. This calculation is the number of completed contacts over the number of contacts plus the number of eligible refusals and noncontacts, and an estimated proportion of the potential contacts that were eligible. Using this procedure, we calculated a 72% response rate for this survey.
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The baseline telephone surveys were completed by women talking with trained and monitored interviewers. The interview lasted about 45 minutes, and included measures of family history, presence of breasts and ovaries, awareness of breast and ovarian cancer, perceived risk of breast and ovarian cancer, worry about breast and ovarian cancer risk, awareness of and view about genetic testing, screening intentions and behaviors, and demographics. Survey measures. Demographic variables assessed included age, race, income, education, marital status, employment status, and health care coverage measures of demographics consisted of simple single items used in our previous research projects. Information on women’s personal history of breast or ovarian cancer and the presence of breasts and ovaries was used to determine both a woman’s likely risk of developing breast or ovarian cancer and her suitability for various cancer screening activities. For these analyses women without breasts or ovaries because of prophylactic surgery were excluded from the dataset. Family history information was provided by women in response to the question ‘‘Has (name of relation; eg, your mother) ever had cancer?’’ If yes, further data were collected on the type of cancer and patient’s age at diagnosis. This allowed for the classification of women as high-risk for a mutation associated with increased risk for breast or ovarian cancer or as at genetically low risk (and thus at approximately average risk for these diseases overall). Women were considered high-risk if they reported at least 1 first-degree relative (eg, a mother, sister, or daughter) affected by breast cancer before the age of 60, or 2 first-degree relatives with breast or ovarian cancer at any age. Women were also considered high-risk if they reported 2 first- or second-degree relatives (eg, aunts, grandparents, half sisters) with breast or ovarian cancer on the same side of the family, or 1 first-degree male relative (eg, father, brother or son) with breast cancer (Table I). Although we did not assess women’s knowledge about cancer at each site women were asked about their awareness of each cancer via questions asking how much they had read or heard about each cancer. Response categories for these questions include ‘‘very little,’’ ‘‘some,’’ ‘‘a fair bit,’’ and ‘‘a lot.’’ Use of genetic testing was assessed by asking women if they’d ever had genetic testing of any sort, and then asking them to specify what kind of genetic testing they received. Responses that indicated testing for breast or ovarian cancer risk, BRCA1 or BRCA2 testing, or responses indicating cancer risk without specifying the test or organ site specifically were assumed to be BRCA1/2 testing for genetic risk for breast/ovarian cancer. Awareness of and interest in genetic testing, were assessed by asking women a series of questions. To assess awareness we asked women
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Table I. Criteria for high-risk designation One first degree relative with breast cancer before 60, or Two first degree relatives with breast or ovarian cancer at any age, or Two second degree relatives with breast or ovarian cancer on same side of the family, or One first degree relative with breast or ovarian cancer and one second degree relative with breast or ovarian cancer on same side of the family, or One first degree male relative with breast cancer
‘‘How much have you read or heard about genetic testing for cancer risk?’’ with response categories ‘‘very little,’’ ‘‘some,’’ ‘‘a fair bit,’’ and ‘‘a lot.’’ Women indicated their interest in getting genetic testing using response categories ‘‘definitely not,’’ ‘‘probably not,’’ ‘‘probably yes,’’ and ‘‘definitely yes.’’ Women’s perceptions of their risk of breast and ovarian cancer, were assessed via 2 items. The breast cancer item asked ‘‘What do you think the chances are that you will have breast cancer someday?’’. The ovarian cancer item was the same except for the organ site of the cancer named. Response categories for these items included ‘‘100%,’’ ‘‘80% to 90%,’’ ‘‘60% to 70%,’’ ‘‘about 50%,’’ ‘‘30% to 40%,’’ ‘‘20% to 30%,’’ ‘‘about 10%,’’ ‘‘about 5%,’’ ‘‘about 1%,’’ and ‘‘0%.’’ For analysis several of these categories were combined. Specifically, all the categories from ‘‘100%’’ to ‘‘about 50%’’ were combined to create a ‘‘50%+’’ category. Women’s use of cancer screening was assessed using a series of questions asking about each of the various forms of screening available. Women were asked whether they have ever had an ultrasound examination of their ovaries to screen for ovarian cancer and if so how often they have had such examinations, whether they have ever had a CA-125 blood test to look for ovarian cancer and if so how often they have had such tests. Although all women in the dataset had breast and ovaries and would thus were at least potentially candidates for cancer screening at both sites, some were not at elevated risk and under the age of 40. Therefore, women were given an option of indicating not only that they were not getting screening but that they believed each of the screening tests were not applicable for them. Results Participating women were generally white (86%), and fairly well educated (85% had completed some college or technical school training after high school; less than 2% had not completed high school). Most reported a moderate income (median household income $30,000 to $49,000), 46% were married or living with a partner, and 66% were employed outside the home. These characteristics are consistent with those of the population from which they were recruited.
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Table II. Characteristics of study sample Demographic Information Age Less than 40 40-50 50+ Race White Other Education Less than high school High school graduate College or technical school training Income Less than $15,000 $15,000 to $29,999 $30,000 to $49,999 $50,000 to $69,999 $70,000 or over Marital status Legally married Living with a partner Not living with a Partner Other Employment Full-time employed Part-time employed Not employed Retired
Average Risk
High Risk
P value
29.78% 31.20% 39.02%
25.00% 32.32% 42.68%
= .43
86.58% 13.42%
84.76% 15.24%
=.52
1.91% 13.39% 84.69%
1.22% 15.85% 82.93%
=.59
6.30% 18.99% 30.36% 19.42% 24.93%
8.07% 15.53% 31.68% 21.74% 22.98%
=.69
31.75% 14.45% 53.38%
30.49% 13.41% 54.88%
0.42%
1.22%
=.56
65.89% 12.34% 10.59% 11.18%
66.46% 9.15% 12.80% 11.59%
=.59
Among the 1,366 women participating in the project 1,202 (88%) were of approximately average risk, and 164 (12%) were considered high risk according to the study criteria. Of these ‘‘high-risk’’ women all but 5 had first or second degree relatives with breast cancer. The remaining 5 reported at least 1 first degree relative with ovarian cancer. In total 16 of the high-risk women reported at least 1 first- or second-degree relative affected by ovarian cancer. The demographic characteristics of high-risk women did not differ from those of approximately average risk in age, race, education, income, marital status or employment (P > .05 for all comparisons). See Table II for additional information. Most (75.6%) of the high-risk women reported having read or heard ‘‘a fair bit’’ or ‘‘a lot’’ about breast cancer. Self-reported levels of awareness of ovarian cancer were, however, considerably lower with only 24.4% of high-risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about ovarian cancer. Less than half (38.4%) of the high-risk women in this sample reported being definitely interested in genetic testing. In addition, levels of awareness of genetic testing were fairly low with only 23.5% of high-risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about genetic testing for cancer risk. The majority of high-risk women also reported perceived risks of breast and ovarian cancer that were unrealistically high. Of these women, 90.7% reported perceived lifetime risks of breast cancer greater than 20%,
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Table III. Awareness and perceived risks of high-risk women
Table IV. Use of genetic testing and cancer screening among women older than 50 according to risk status
High Risk
Average Risk
Statistical Significance (P)
3 (4.5%) 67 (94.5%)
21 (4.5%) 446 (94.5%)
= .94
68 (97.1%) 2 (2.9%)
457 (97.4%) 12 (2.6%)
= .88
4 (6.0%) 63 (94.0%)
32 (6.9%) 435 (93.1%)
= .53
9 (10.8%) 74 (89.2%)
61 (13.4%) 395 (86.6%)
= .79
High Risk How much have you read or heard about breast cancer? Very little Some A fair bit A lot How much have you read or heard about ovarian cancer? Very little Some A fair bit A lot How much have you read or heard about genetic testing for cancer risk? Very little Some A fair bit A lot Perceived risk of breast cancer: Less than 20% 20-50 50+ Perceived risk of ovarian cancer: Less than 20% 20-50 50+ Interest in genetic testing: Definitely not Probably not Probably yes Definitely yes
Risk Status 4.88% 19.51% 35.98% 39.63% 35.98% 39.63% 14.63% 9.76% 34.36% 41.10% 21.47% 3.07% 9.30% 58.60% 32.10% 36.06% 57.14% 6.80% 3.05% 12.80% 45.73% 38.41%
and approximately one-third (32.1%) reported perceived risks of breast cancer greater than 50%. About one-third (36.0%) of these women reported perceived risks of ovarian cancer less than 20% and 6.8% reported perceived risks of ovarian cancer greater than 50%. Characteristics of high risk women are also shown in Table III. Although average risk women tended to report similar levels of perceived risk for both cancers, only 21.9% of the participating high-risk women reported similar levels of perceived risks for the 2 cancers. The high-risk women appeared to know that their risk for ovarian cancer is much lower than their risk for developing breast cancer. Seventy three percent of the high-risk women reported perceived risks for breast cancer higher than their perceived risk for ovarian cancer. The kind of cancer reported by a woman as part of her family history appears to predict differences in levels of perceived risk of breast cancer. Among the high-risk women with a family history including at least 1 relative with breast cancer (n = 155) 75.5% reported higher levels of perceived risk for breast cancer than they did for ovarian cancer. Among the 5 women with family histories including only ovarian cancer; 3 reported perceived risks
Genetic testing Yes No Mammography use Yes No CA-125 blood test Yes No Ultrasound use Yes No
of ovarian cancer greater than those of breast cancer and 2 reported the same level of perceived risk for both cancers. Overall, use of genetic testing to clarify risk was small: only 4.5% (n = 3) of the high-risk women reported having received genetic testing. Twenty-one (also 4.5%) of those who were not at high-risk also reported having received genetic testing. The high-risk women did report use of mammography with 50% of the high-risk women reporting regular use of mammography for breast cancer screening every year. Almost all (97.1%) of the 70 high-risk women over age 50 reported recent mammography use within the past 2 years. A similar percentage (97.4%) of the women over 50 who were not high risk (n = 469), however, also reported recent mammography use. Rates of reported use of ultrasound and CA-125 blood tests for ovarian cancer screening were lower (less than 3% of the women in the high-risk group reported using either test regularly once a year). When the sample was limited to women over the age of 50; 6.0% of high-risk women and 6.9% of those who were not high risk reported use of CA-125 testing, while 10.8% of the high-risk and 13.4% of those who were not high-risk reported use of ultrasound for ovarian cancer screening. These percentages are not statistically significantly different. Table IV shows use of genetic testing and cancer screening by high and average risk women over 50 years of age. Discussion Women with high-risk family histories generally reported having read or heard ‘‘a fair bit’’ or ‘‘a lot’’ about breast cancer, despite this their knowledge about their risk for the disease was poor and these women reported unrealistically high levels of perceived risk. Women at genetic risk for breast cancer are also at high-risk for ovarian cancer. Despite this, self-reported levels of awareness of ovarian cancer were very low. Less than 30% of high-risk women reporting having heard ‘‘a fair
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bit’’ or ‘‘a lot’’ about ovarian cancer. Despite, or perhaps because of, their lack of knowledge most high-risk women also overestimate their risk for ovarian cancer. As has been reported in prior studies,23 high-risk women report considerable interest in genetic testing. In this study we found 38.4% of high-risk women reported being interested in testing. Levels of awareness of genetic testing, were, however, low with less than 25% of high risk women reporting having heard ‘‘a fair bit’’ or ‘‘a lot’’ about genetic testing for cancer risk. This suggests that in spite of interest and media coverage of issues related to BRCA1 and BRCA2 testing many high-risk women are not sufficiently well informed about testing to make informed decisions about their use of this technology. Few, (4.5%) of the high-risk women in this population sample reported having received a genetic test for cancer. This percentage was identical to the percentage of women who were not high-risk (4.5%). That similar percentages of high- and average-risk women have received genetic testing for cancer suggests potential problems in the health care system as genetic testing is really most appropriate for women who come from families with multiple affected relatives. Fortunately, women do appear have some awareness of the value of mammography as a means of screening for breast cancer 97% of high-risk women (over the age of 50) reported regular use of mammography for breast cancer screening. Unfortunately, very few of the high-risk women under the age of 50 reported screening use although such screening would generally be recommended for them. Rates of mammography use among high-risk women were not higher than rates of use by women of average risk. This finding is not unique. Although some studies have found women with a family history of breast cancer use mammography more than those without a family history24,25 studies focusing on higher risk women have not always found this to be the case.24,26,27,28 Overall, when higher levels of use have been found differences in use between high- and average-risk women have been small to moderate.24,25 This pattern of findings suggests that although high-risk women report high levels of awareness regarding breast cancer and overestimate their risk, family history associated high-risk status does not of itself spur women to get additional screening or screening at younger ages as has been recommended for women at high-risk. Physicians may need to ask women about their family history and encourage use among those they find to be at high risk if they wish to see their high-risk patients getting early or intensive screening such as is sometimes recommended for these women. Ovarian cancer screening is even more seriously underused. Although ovarian cancer screening is not recommended for average risk woman because of lack of evidence for it’s effectiveness, high-risk women who may have a genetic mutation are at elevated risk for ovarian
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cancer ovarian cancer screening is recommended for these women.22 Rates of reported use of ultrasound and CA-125 blood tests for ovarian cancer screening were less than 5% in the sample overall and only 6% (CA-125) and 11% (ultrasound) for high-risk women over 50. Although our definition of high-risk was lenient in this study and not all the women categorized as high-risk here would be good candidates for ovarian cancer screening, these rates of use are low. These findings and those of other population-based studies of high risk women29 suggest that outside of high-risk screening programs high-risk women are not be getting the screening services recommended for them. There are limitations to the study methods which must be considered when drawing conclusions from the data. First, this study was conducted in an urban/suburban area in a single region of the country where the population is generally well educated and predominantly white. There are regional variations in health care delivery and these could limit the generalizability of the results to women living in rural areas and other regions of the country. As less educated, and minority women and those living in rural areas are frequently medically under-served the results of this study probably understate the problem of lack of information and failure to use screening likely found among high-risk women nationwide. In addition, our response rate was 72%; although this is commonly considered reasonable, the results to do not include responses from approximately 28% of eligible women. These women may share characteristics that caused them to choose not to participate in research of this type. We are hopeful that this is not the case however, as the demographic data from this sample when compared with census derived data for the catchment area indicated that the sample is likely representative. An additional limitation arises from the fact that mammography and other screening service use was assessed in this study via self-report and these reports were not confirmed via contact with providers. Similarly reports of a family history of cancer were not confirmed via requests for medical records for the affected relative. Self-report data on mammography has generally been found to be quite accurate, especially reports of mammography within 1 year of an interview.30,31 The validity of self-reports of CA-125 blood tests and sonography are unknown. The accuracy of women reports of a family history of cancer has been examined and these reports have generally been found to be fairly accurate with 83% to 88% of reported cancers in first degree relatives being confirmed on request of records.32,33,34 Reports of a family history of cancer in second degree relatives have been found to be less accurate.33 It is not known how accurately people can report the age at which a relative was diagnosed with cancer. Overall, these findings suggest that high-risk women are not necessarily getting the
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information they need about their risk for breast and ovarian cancer and may benefit from genetics education interventions designed for them. Physicians should not assume that high-risk women are getting all appropriate ovarian cancer screening tests, or that if they are not, they are doing so after making an informed decision about the risks and benefits of screening considering their risk status. It is unclear why there should be so few differences in cancer screening use associated with risk status. Possibilities include failure of primary care physicians to ask about family history and to use family history information to inform patients of their risk status and direct care based on this information. Another would be failure to consider both ovarian and breast cancer together when determining risk and making recommendations for future care. In situations such as BRCA1/2 where a mutation is associated with cancer at multiple sites educational efforts may particularly important as women may not assume that a family history of cancer at one organ site puts them at risk for cancer at not only that but also another organ site. Our data suggest this is a possible issue but should be considered essentially anecdotal on this point as the number of high-risk women with affected relatives with ovarian cancer was limited and the number with family history of ovarian but not breast cancer extremely limited. REFERENCES 1. 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 Biomark Prevent 1999;8:369-75. 2. Lerman C, Schwartz M. Adherence and psychological adjustment among women at high risk for breast cancer. Breast Cancer Res Treat 1993;28:145-55. 3. Narod SA, Feunteun J, Lenoir G, et al. Familial breast- ovarian cancer locus on chromosome 17ql2-23. Lancet 1991;338:82-3. 4. American Society of Clinical Oncology. Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility. J Clin Oncol 14 1996;1730-6. 5. American Cancer Society. American Cancer Society Cancer Facts and Figures—1998. Atlanta, GA: American Cancer Society Inc, 1998. 6. Foulkes W, Glendon G, Narod S. Family history and risk of ovarian cancer. JAMA 1995;274:383. 7. Frank TS, Manley SA, Olopade OI, et al. Sequence analyses of BRCA1 and BRCA2: Correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 1998;16:2417-25. 8. Ponder BAJ, Easton DF, Peto J. Risk of ovarian cancer associated with a family history. In: Sharp F, Leake R, editors. Ovarian Cancer. London, Chapman & Hall Ltd; 1990. p. 3-6. 9. Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCAlmutation carriers. Lancet 1994;343:692-5. 10. Easton DF, Ford D, Bishop DT, et al. Breast and ovarian cancer incidence in BRCAl-mutation carriers. Am J Human Genet 1995; 56:265-71.
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11. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401-8. 12. Satagopan JM, Offit K, Foulkes W, et al. The lifetime risks of breast cancer in Ashkenazi Jewish Carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prevent 2001;10:467-73. 13. 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 1997;277:997-1003. 14. Struewing JP, Watson P, Easton DF, et al. Prophylactic oo-phorectomy in inherited breast/ovarian cancer families. J Nat Cancer Instit Mono 1995;17:33-5. 15. Carlson K, Skate S, Singer D. Screening for ovarian cancer. Ann Intern Med 1994;121:124-32. 16. Jacobs I, Davies AP, Bridges J, et al. Prevalence screening for ovarian cancer in postmenopausal women by CA125 measurement and ultrasonography. Br Med J 1993;306:1030-5. 17. Jacobs IJ, Skates S, Davies AP. Risk of diagnosis of ovarian cancer after raised serum CA-125 concentration: A prospective cohort study. Br Med J 1996;313:1355. 18. Jacobs I, Stabile I, Bridges J, et al. Multimodal approach to screening for ovarian cancer. Lancet 1988;336:268-71. 19. Bast RC Jr, Boyer CM, Xu FJ, et al. Molecular approaches to prevention and detection of epithelial ovarian cancer. J Cell Biochem 1995;23(suppl):219-22. 20. Campbell S, Bhan V, Royston P, et al. Transabdominal ultrasound screening for early ovarian cancer. Br Med J 1989;299:1363-7. 21. Rosenthal A, Jacobs I. Ovarian cancer screening. Semin On col 1998;25:315-25. 22. Ovarian cancer: Screening, treatment, and follow-up. NIH Consensus Statement Apr. 5-7 1994;12:1-30. 23. Burke W, Culver JO, Bowen D, et al. Genetic counseling for women with an intermediate family history of breast cancer. Am J Med Genet 2000;90:361-8. 24. Hailey BJ. Family history of breast cancer and screening behavior: An inverted U-shaped curve? Medical Hypoth 1991;36:397-403. 25. McCaul KD, Branstetter AD, Schroeder DM, et al. What is the relationship between breast cancer risk and mamniography screening? A meta-analytic review. Health Psychol 1996;15:423-9. 26. Vogel VG, Graves DS, Vernon SW, et al. Mammographic screening of women with increased risk of breast cancer. Cancer 1990;66:1613-20. 27. Kaplan KM, Weinberg GB, Small A, et al. Breast cancer screening among relatives of women with breast cancer. Am J Public Health 1991;81:1174-8. 28. Drossaert CC, Boer H, Seydel ER, et al. Perceived risk, anxiety, mammogram uptake, and breast self-examination of women with a family history of breast cancer: The role of knowing to be at increased risk. Cancer Detect Prevent 1996;20:76-85. 29. Dresher C, Holt SK, Andersen MR, et al. Reported ovarian cancer screening among a populations based sample in Washington State. Obstet Gynecol 2000;96:70-4. 30. King ES, Rimer BK, Trock B. How valid are mammography selfreports? Am J Public Health 1990;80:1386-8. 31. McGovern PG, Lurie N, Margolis KL, et al. Accuracy of self-report of mammography and Pap smear in a low-income urban population. Am J Prevent Med 1998;14:201-8. 32. Napier JA, Metzner H, Johnson BC. Limitations of morbidity and mortality data obtained from family histories—A report from the Tecumseh community health study. Am J Public Health 1972;62:30-5. 33. Love RR, Evans AM, Josten DM, et al. The accuracy of patient reports of a family history of cancer. J Chronic Dis 1985;38:289-93. 34. Bondy ML, Strom SS, Colopy MW, et al. Accuracy of family history of cancer obtained through interviews with relatives of patients with childhood sarcoma. J Clin Epidemiol 1994;47:89-96.