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Does This Patient Have a Family History of Cancer?: An Evidence-Based Analysis of the Accuracy of Family Cancer History

Does This Patient Have a Family History of Cancer?: An Evidence-Based Analysis of the Accuracy of... Abstract Context A family history of certain cancers is associated with an increased risk of developing cancer. Both cancer screening and genetic services referral decisions are often based on self-reported pedigree information. Objective To determine the accuracy of self-reported family cancer history information. Data Sources English-language articles were retrieved by searching MEDLINE (1966-June 2004) using Medical Subject Headings family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. Additional articles were identified through bibliography searches. Study Selection Original studies in which investigators validated self-reported family history by reviewing the identified relatives' medical records, death certificate, or cancer registry information were included, as well as studies that evaluated breast, colon, ovarian, endometrial, and prostate cancers. Data Extraction Two of the 3 investigators independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of self-reported family cancer history information. Only data from studies that evaluated both positive and negative family cancer histories were included within the analyses. A total of 14 studies met the search criteria and were included in the review. Data Synthesis For patients without a personal history of cancer, the positive and negative LRs of a family history of the following cancers in a first-degree relative were 23.0 (95% confidence interval [CI], 6.4-81.0) and 0.25 (95% CI, 0.10-0.63) for colon cancer; 8.9 (95% CI, 5.4-15.0) and 0.20 (95% CI, 0.08-0.49) for breast cancer; 14.0 (95% CI, 2.2-83.4) and 0.68 (95% CI, 0.31-1.52) for endometrial cancer; 34.0 (95% CI, 5.7-202.0) and 0.51 (95% CI, 0.13-2.10) for ovarian cancer; and 12.3 (95% CI, 6.5-24.0) and 0.32 (95% CI, 0.18-0.55) for prostate cancer, respectively. Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives. Conclusions Patient-reported family cancer histories for first-degree relatives are accurate and valuable for breast and colon cancer risk assessments. Negative family history reports for ovarian and endometrial cancers are less useful, although the prevalence of these malignancies within families is low. Clinical scenario A 35-year-old woman presents for an initial visit and during the medical interview mentions that her mother and grandmother had breast cancer. She reports that her mother's cancer was diagnosed at age 42 years and she believes that her grandmother, on her mother's side, was diagnosed in her 30s. Because of her family history, she is concerned about her risk of developing breast cancer. Despite having no symptoms of breast cancer, she wonders at what age she should start having mammograms and whether she should have genetic testing. Why is it important to record an accurate family history of cancer? Quiz Ref IDIndividuals with a positive family history for certain kinds of cancers can have an increased risk of developing cancer themselves.1,2 Two meta-analyses found relative risks of 2.1 (95% confidence interval [CI], 2.0-2.2) for breast cancer3 and 3.1 (95% CI, 2.6-3.7) for ovarian cancer4 in women with affected first-degree relatives. Similar higher risks have been noted for endometrial cancer,5-7 colon cancer,7-10 and prostate cancer.11-13 Accurate reporting of family history helps risk stratify patients, which in turn determines screening and prevention interventions. Individuals with family histories that are suggestive of a possible hereditary cancer syndrome (Box 1)14-17 are typically considered at high or very high risk of developing cancer; whereas, individuals with positive family cancer histories for certain cancers but not meeting these specified criteria for hereditary cancer are generally at a moderately increased risk of developing cancer when compared with the general population. Several organizations have recommended initiating screening earlier, more frequently, or both in patients at moderately increased risk of developing cancer based on their family history.18-27 Guidelines have also been published regarding the management of individuals who are at high cancer risk.26,28-30Quiz Ref IDA family history of malignancy will not only influence cancer screening initiation and frequency but also can affect treatment strategies. Family histories affect decisions about cancer chemoprevention31,32 and those individuals identified as being at very high risk may also be considered for risk-reducing surgeries.33 Likewise, algorithms that predict individuals who might be candidates for genetic testing rely almost exclusively on family history information.14,16 Box 1. Examples of Clinical Diagnostic Criteria for 2 Familial Cancer Syndromes and Recommendations Regarding Genetic Testing for Cancer Susceptibility Hereditary Nonpolyposis Colon Cancer (HNPCC)14,15 All of the following criteria should be present: At least 3 relatives must have a cancer associated with HNPCC (colon, endometrial, ovarian, stomach, small bowel, hepatobiliary, ureter, renal-pelvis, brain). One should be a first-degree relative of the other 2. At least 2 successive generations should be affected. At least 1 of the relatives with cancer associated with HNPCC should have received the diagnosis before age 50 years. Hereditary Breast/Ovarian Cancer16* Any of the following criteria should be present: Two breast cancers in a first- or second-degree relative and mean age at diagnosis of 40 years. One breast cancer and 1 ovarian cancer in a first- or second-degree relative and mean age at diagnosis of 41 to 50 years. Two or more breast cancers and 1 ovarian cancer in a first- or second-degree relative. Ovarian cancer in 2 relatives. American Society of Clinical Oncologists Policy Statement on Genetic Testing17 Indications for genetic testing: The individual has personal or family history features suggestive of a genetic cancer susceptibility condition. The test can be adequately interpreted. The results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. *Identified relatives must be on the same side of the family (either maternal or paternal relatives). Because many screening and prevention strategies for cancer rely on self-reported family history information, inaccurate information could potentially result in inappropriate care. A false-negative family cancer history results in an underestimation of cancer risk and missed opportunities for cancer screening. Failure to collect adequate family history information and appropriate management of a patient's cancer risk may result in substandard care and in some cases has resulted in malpractice litigation.34 Conversely, a patient's false belief in a positive family cancer history can cause stress35 and when compounded by the physician's overestimation of risk may lead to unnecessary procedures or surgeries.36 The overestimation of cancer risk based on pedigree data creates unneeded referrals for genetic testing or cancer risk counseling.37,38 The increased availability and demand for genetic services require an even more important role for primary care physicians in recording an accurate family history39,40; however, many physicians lack adequate training in genetics to accurately identify and refer appropriate candidates for genetic services.41,42 Additionally, with direct-to-consumer advertising for genetic testing now a reality,43 accurate family history collection and cancer risk assessment by primary care physicians might help decrease the likelihood of inappropriate referrals for genetic counseling and testing. Few data exist describing how often inaccurate risk assessments are made based on faulty pedigree data. In 1 retrospective study35 that examined patients referred to 2 cancer genetic clinics, patient management was changed in 23 (11%) of 213 patients after their previously reported family history information was found to be inaccurate. In 15 of these patients, screening was thought to be unnecessary, although in 8 patients cancer risk was determined to be greater than initially believed. Further studies have supported these findings, with 1 study44 determining that 6 (5%) of 120 patients referred to a cancer clinic had changes in management after confirmation of the family cancer history revealed discrepancies. In most of these patients, the cancer risk had been overestimated. Prevalence of a Positive Family History of Specific Familial Cancers The prevalence of a family history of cancer varies depending on the cancer type. The prevalence of a family history of breast cancer has been estimated to range from 5% to 22%,45-48 colon cancer 2.0% to 9.4%,8,45,46 ovarian cancer 1.1% to 3.5%,45,46,48 endometrial cancer 0.5% to 1.4%,45,46 and prostate cancer 4.6% to 9.5%.11,13,46,49 Most of this variation is due to methodology and study population. Some studies included distant relatives in the definition of a positive family history, while other studies have focused only on first-degree relatives. Variability in rates also occurs when the results are derived from the general population as opposed to patients referred to cancer or genetic centers, which have higher prevalence rates. How to Elicit a Family History Family history information is important for risk assessment in numerous chronic medical conditions in addition to cancer, such as diabetes mellitus and cardiovascular disease; therefore, eliciting a family cancer history can serve as a model for collecting family history information for other disorders. Typically, family history information is collected directly from the patient or from screening questionnaires filled out by the patient. Alternatively, the patient's parent or another family member may provide the information. Screening questionnaires are often either a list of relatives, with space to provide information on overall health, age, and cause of death, or a list of adult-onset diseases with space to list the affected relative. Disease history should be collected on both first-degree relatives (mother, father, sisters, brothers, children) and second-degree relatives (maternal and paternal grandparents, aunts, uncles, nieces, and nephews). It is important to inquire about various types of cancers as certain hereditary cancer syndromes can be identified by specific cancers that cluster together within families (Box 1), such as endometrial with colon50 and breast with ovarian.51,52 If the initial screening interview or questionnaire reveals a potential familial predisposition to a particular disease, the family history should be expanded. Although establishing the numbers of both affected and unaffected relatives is important for determining penetrance and predicting the likelihood of gene mutations, this information for primary care physicians would seldom influence cancer screening decisions. Quiz Ref IDFor affected relatives, documenting the age at cancer diagnosis is important as patients developing cancer at ages significantly earlier than typically expected increases the possibility of a hereditary cancer syndrome. Inaccurate reporting of ages at diagnosis for breast cancer can have a considerable influence on risk prediction in families with fewer than 4 affected relatives.53 A 3-generation pedigree, displayed graphically in the Figure 1, offers a convenient symbolic method of summarizing information. Because of prior inconsistencies in pedigree symbol usage, the Pedigree Standardization Task Force, organized through the National Society of Genetic Counselors, has proposed recommendations for a standardized pedigree nomenclature.54 When recording a pedigree, particularly for breast and gynecological cancers, it is important to inquire about disease in both maternal and paternal lineages as mutations can be transmitted through either parent. When collecting information on second-degree relatives, it is important to note the lineage to which the relative belongs (such as paternal vs maternal grandparents) as the degree of risk might vary if affected relatives do not belong to the same lineage. A brief reference for physicians on the family medical history has been prepared by the American Medical Association and is available at http://www.ama-assn.org/ama/pub/category/2380.html. For a more detailed account, the authors recommend consulting The Practical Guide to the Genetic Family History by Bennett.55 Family history information can be collected during a patient care visit or outside of the clinical encounter. Methods of collecting family history information outside of the clinical encounter can include paper questionnaires,56 computer questionnaires in kiosks within a clinic waiting area,37 Web-based electronic collection, and interviews by health care professionals. The optimal means of collection has not been determined. Methods Two of the authors (H.J.M. and D.R.S.) performed independent searches of the MEDLINE database for English-language articles dated 1966 to June 2004 from the PubMed search engine. The following Medical Subject Headings were used: family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. We also searched using textwords accuracy, sensitivity, specificity, and family history combined with the conditions breast cancer, colon cancer, ovarian cancer, prostate cancer, endometrial cancer, or uterine cancer. We specifically included cancers that were likely to be commonly encountered by primary care physicians and whose management might be altered based on family history information. The reviewers evaluated article abstracts and chose studies for full-text review based on the abstract. We searched the bibliographies of all retrieved articles to identify additional sources. Articles were included if they were original articles describing the accuracy of the site-specific family history for the prespecified cancers and contained a criterion standard. Studies presenting aggregate data (all cancer types combined into a single measure) for self-reported family cancer history information were excluded. For purposes of this study, the criterion standard for a positive family history of cancer required verification from the identified relative's medical record, physician, or death certificate, and/or verification within a population cancer registry. For studies to be included in our analysis, verification of a negative family history for cancer had to have been performed. Thus, if a study participant reported that a relative had no history of breast cancer, the relative's medical records, death certificate, if applicable, or local cancer registry were examined for verification of this report. The completeness of case-findings within tumor registries varied, with 83% to 99% of cancers identified through medical record reviews and patient interviews also being present within the registry.57-61 Specific cancer sites are correctly recorded within the registry in 93% to 97% of cases. Forty-nine percent of discrepancies within tumor registries result from changes in an initial diagnosis with a failure to update registry information.61 For breast cancer, the sensitivity and specificity of tumor registries are high.62 Other tumors listed within registries have similar high sensitivities.63,64 The National Program of Cancer Registries of the Centers for Disease Control and Prevention has created a system that provides the rationale for accepting these data in studies that attempt validation of the patient's family history.65 Although death certificates probably lack the accuracy of tumor registries, the poorer performance of death certificates is more likely attributed to poor sensitivity (the death certificates do not record the information when in fact the decedent had cancer).66 Based on autopsy studies, the death certificate is estimated to have a sensitivity of 87% for identifying cancer.67 We identified 22 studies from our search using the listed criteria.44,68-88 Of these, only 7 provided information on both the test characteristics of a positive and negative report of a family history.71,73,74,76,78-80 One study specifically assessed pedigrees suggestive of hereditary nonpolyposis colorectal cancer (HNPCC)76 and was included within the analysis. Sensitivity and specificity were determined for the family history interview for HNPCC but this information was not combined with other colon cancer studies. We used techniques described from previous "Rational Clinical Examination" articles to determine study quality and all 7 evaluated studies were assigned a quality score of C,89 which reflects a study with an independent blind comparison of sign or symptom and a criterion standard of diagnosis among nonconsecutive patients suspected of having the target condition. Because the population studied could influence reporting accuracy, test characteristics were calculated separately for individuals with a personal history of cancer as well as individuals without a personal history of cancer. Sensitivity and specificity of patient self-report of a family history of cancer and likelihood ratios (LRs) of a positive or negative report were calculated based on raw data supplied by the original articles that met our search criteria. Confidence intervals for LRs were computed using previously described methods.90 We used random effects summary measures for combining the data because this provided a broad range of possible data that display the uncertainty around the point estimates. The summary measures described this uncertainty better than the simple range of possible data from the original studies. For colon cancer, 1 study76 was not included within the summary LRs because it specifically evaluated the family history for HNPCC rather than colon cancer in general. Results Precision Precision reflects the reproducibility of a measurement. Assessing the precision of the family history interview is challenging as it can be influenced by both patient and physician factors. Although we were unable to identify any studies assessing health care physician interrater or intrarater reliability for the family history assessment, 1 study91 in breast cancer examined the reliability of patient self-report. In this nested case-control study,91 comparisons were made between self-reported family history information in women before the development of the disease and after the development of the disease. Follow-up surveys were completed 2 years after the initial survey. Both women who had developed breast cancer and women who had not developed breast cancer were surveyed. The agreement for maternal history of breast cancer was κ = 0.92 and κ = 1.00 for cases and controls, respectively; and for a history of breast cancer in a sister, κ = 0.65 and κ = 0.88, respectively. Although the study did not assess whether a real change in family history might have occurred during the study period, these results suggest that self-reported family breast cancer history is probably only slightly influenced by recall bias. Patient precision regarding the family history interview for other cancers has not been reported. Accuracy Accuracy represents how well a particular test measures the value it is intending to measure. Seven studies concerning family history were ultimately included in this analysis (Table 1).71,73,74,76,78-80 Three studies collected family history from personal patient interviews,73,74,79 while the other 4 relied on a self-completed survey.71,76,78,80 Four studies solely relied on cancer registry data as their criterion standard73,74,79,80; 2 studies used a combination of medical records and death certificates,71,78 while the remaining study used all 3 sources as its criterion standard.76 Only information for first-degree relatives was extracted. For individuals affected with cancer (Table 2), the positive and negative LR of a self-reported family cancer history in a first-degree relative were 23.0 (95% CI, 8.1-64.0) and 0.29 (95% CI, 0.13-0.67) for colon; 41 (95% CI, 23-75) and 0.07 (95% CI, 0.03-0.13) for breast; 20.0 (95% CI, 4.3-89.0) and 0.55 (95% CI, 0.35-0.86) for endometrial; 44 (95% CI, 15-132) and 0.21 (95% CI, 0.12-0.37) for ovarian; and 24.0 (95% CI, 2.3-262.0) and 0.25 (95% CI, 0.16-0.39) for prostate cancers, respectively. For patients without a personal history of cancer (Table 3), the positive and negative LRs of a family history for the following cancers in a first-degree relative were 23.0 (95% CI, 6.4-81.0) and 0.25 (95% CI, 0.10-0.63) for colon; 8.9 (95% CI, 5.4-15.0) and 0.20 (95% CI, 0.08-0.49) for breast; 14.0 (95% CI, 2.2-83.4) and 0.68 (95% CI, 0.31-1.52) for endometrial; 34.0 (95% CI, 5.7-202.0) and 0.51 (95% CI, 0.13-2.10) for ovarian; and 12.3 (95% CI, 6.5-24.0) and 0.32 (95% CI, 0.18-0.55) for prostate cancers, respectively. The estimates for sensitivity, specificity, and LRs for unaffected individuals for prostate, breast, endometrial, and ovarian cancers are based on data from a single study by Kerber and Slattery.74 Of the remaining 15 studies, we excluded 8 studies81-88 because the tumor data were presented in aggregate (ie, family history of any cancer) or were unclear; therefore, we were unable to extrapolate site-specific numbers. Seven studies evaluated only the positive predictive value of self-reported family history information for breast, colon, ovarian, prostate, and endometrial cancers (Table 4). Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives. Individuals with personal histories of cancer tended to report family histories with a greater positive predictive value, although the number of studies evaluating unaffected individuals was limited. Common Reasons for False-Positive or False-Negative Reports In cancers in which patients are likely to be accurate in their report, such as breast cancer, case reports have indicated that false-positive reports are associated with malingering, problems with patient-physician communication, or prior history of benign breast disease being reported as malignant.36 Other common reasons for false-positive reports of family cancer history result from confusion based on primary vs metastatic disease.68,92 This confusion has been described with false reports of primary liver cancer as well as central nervous system cancers. Cancers that are frequently overreported include melanoma, which is incorrectly reported in almost half of reports,93 and non–colonic gastrointestinal malignancies.35 Quiz Ref IDSeveral factors relate to a false-negative report of a family history of cancer. In 1 study,94 older patients and non–white respondents were more likely to underreport a family history of cancer. Another study74 demonstrated that older patients were more likely to falsely report a negative family history of cancer, while patient sex and education level have little effect on the accuracy of reporting. Specific cancers with high rates of false-negative reporting include central nervous system tumors and hematological malignancies.94 Other Means for Collecting Family History Information and Ways to Improve Family History Data Collection Several barriers exist for the collection of family history information. Patient specific factors that might result in poor pedigree collection include poor family communication, family myths, or individual spiritual beliefs. For physicians, probably the most significant barrier is time. Although a comprehensive family history assessment can take 15 to 30 minutes,95 the average primary care visit lasts only 16 minutes.96 Several alternative methods that involve collecting this information outside the context of the clinical visit may facilitate the collection of family history information. These other methods include self-completed patient paper surveys, computer-based tools, and personal visits arranged solely for pedigree collection. Family history questionnaires offered outside of a clinical visit confer several theoretical advantages to visit-based pedigree assessment.97 Besides saving clinic time, patients can consult with family members to check the accuracy of the information, which can then be reviewed and integrated into a clinic appointment when relevant. The data from a questionnaire developed in Switzerland compared with information found within 2 population-based cancer registries exhibited sensitivities of 74% and 85% and specificities of 97%.56 Family history assessment tools (Box 2) have also been developed to assist physicians in determining which individuals might be candidates for genetic testing.98 Box 2. Selected Web Sites for Cancer Risk Calculators Methods for Estimating Cancer Risk Various cancer sites: http://www.yourcancerrisk.harvard.edu Breast Cancer Risk Assessment tools: http://bcra.nci.nih.gov/brc/start.htm; http://www.halls.md/breast/risk.htm Methods for Estimating the Likelihood of aBRCAMutation BRCAPRO statistical model: http://www3.utsouthwestern.edu/cancergene/ Mutation prevalence tables: http://www.myriadtests.com/provider/mutprev.htm Computerized genograms can also be effective and convenient tools for both patients and physicians.99-101 These tools offer the benefits of paper-based systems and, through clinical decision support, educate patients and offer guidance to physicians.102-104 Sweet et al37 compared family history information obtained by physicians at a comprehensive cancer clinic with those directly entered by patients into a computer program. Patients were then determined to be "high risk" for cancer based on pedigree information collected from either the computer program or information recorded within the medical record. Of 362 computer entries, 69% had some form of family history information recorded within their medical record. A total of 101 patients were considered high-risk based on their pedigree information collected from the computer program but only 69 of these patients had information recorded within their medical record to confirm this high risk. Special visits outside of the clinical encounter have also been evaluated as a means to obtain family history information. In 1 study,105 patients observed at a single primary care practice were invited to a special visit designed to collect detailed family history information. Ten percent of patients observed in the pedigree clinic had a family history of cancer (breast, colon, melanoma, or thyroid) and some patients were referred for further care based on their pedigree. Patients were less anxious about their family history after the special visit, but this effect was not sustained beyond 12 weeks. A major limitation of the study was the poor attendance to the special clinic; only 16% of invited patients attended. Scenario resolution This patient's pretest probability of having a positive family history of breast cancer before her clinical interview can be estimated at 22%.48 After considering her self-reported pedigree, her posttest probability for a family history of breast cancer increased to 71% (95% CI, 60%-81%) (Table 5). Based on the family history information presented, it is likely that this woman does in fact have a positive family history for breast cancer and that seeking confirmatory evidence is unlikely to offer any additional gain. This patient has 2 relatives affected with breast cancer, both diagnosed before 50 years and 1 a first-degree relative. Using online mutation prevalence tables (Box 2), this woman's risk estimate of harboring a deleterious mutation for either BRCA1 or BRCA2 was 10% and a referral was recommended to a specialized cancer risk assessment program for counseling on genetic testing.106 During pretesting counseling, she learned of the potential limitations of testing on a presymptomatic individual without a known deleterious mutation. The genetic counselor suggested testing 1 of her affected relatives first to produce a more informative test. The patient noted that her maternal grandmother is no longer alive and she is not particularly close to her mother and unsure if her mother would be willing to undergo testing. After pretesting genetic counseling, the patient decided not to be tested for a BRCA1 or BRCA2 mutation and plans to broach the subject of testing with her mother. Based on this patient's family history, clinical breast examinations every 6 months is prescribed and the patient is shown how to perform monthly self-breast examinations. Mammography screening is initiated and an appointment is scheduled. The bottom line Quiz Ref IDThe family history assessment is taking on greater importance as high-risk individuals are being offered earlier screening interventions and risk-reducing therapies. Cancer family histories acquired on first-degree relatives for breast and colon cancer are likely to represent true positives and true negatives for the disease and may not require further evaluation to substantiate. However, other cancers with a familial disposition are less accurately reported. References 1. Lynch HT, Brodkey FD, Lynch P. et al. Familial risk and cancer control. 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Evaluation of the family history collection process and the accuracy of cancer reporting among a series of women with endometrial cancer. Clin Cancer Res.2002;8:1849-1856.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12060627&dopt=AbstractGoogle Scholar 82. Koch M, Hill GB. Problems in establishing accurate family history in patients with ovarian cancer of epithelial origin. Cancer Detect Prev.1987;10:279-283.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3568026&dopt=AbstractGoogle Scholar 83. Douglas FS, O'Dair LC, Robinson M. et al. The accuracy of diagnosis as reported in families with cancer: a retrospective study. J Med Genet.1999;36:309-312.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10227399&dopt=AbstractGoogle Scholar 84. 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J Natl Cancer Inst.1998;90:543-544.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9539252&dopt=AbstractGoogle Scholar 88. Bondy ML, Strom SS, Colopy MW, Brown BW, Strong LC. Accuracy of family history of cancer obtained through interviews with relatives of patients with childhood sarcoma. J Clin Epidemiol.1994;47:89-96.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8283198&dopt=AbstractGoogle Scholar 89. Salkind AR, Cuddy PG, Foxworth JW. Is this patient allergic to penicillin? an evidence-based analysis of the likelihood of penicillin allergy. JAMA.2001;285:2498-2505.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11368703&dopt=Abstract.Google Scholar 90. Simel DL, Samsa GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol.1991;44:763-770.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1941027&dopt=Abstract.Google Scholar 91. Garbers V, Toniolo PG, Taioli E. Changes in self-reported family history of breast cancer with change in case-control status. Eur J Epidemiol.2001;17:517-520.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11949722&dopt=Abstract.Google Scholar 92. Novakovic B, Goldstein AM, Tucker MA. Validation of family history of cancer in deceased family members. J Natl Cancer Inst.1996;88:1492-1493.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8841026&dopt=Abstract.Google Scholar 93. Weinstock MA, Brodsky GL. Bias in the assessment of family history of melanoma and its association with dysplastic nevi in a case-control study. J Clin Epidemiol.1998;51:1299-1303.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10086823&dopt=Abstract.Google Scholar 94. Desai MM, Bruce ML, Desai RA, Druss BG. Validity of self-reported cancer history: a comparison of health interview data and cancer registry records. Am J Epidemiol.2001;153:299-306.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11157418&dopt=Abstract.Google Scholar 95. Loescher LJ. The family history component of cancer genetic risk counseling. Cancer Nurs.1999;22:96-102.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9990765&dopt=Abstract.Google Scholar 96. Blumenthal D, Causino N, Chang YC. et al. The duration of ambulatory visits to physicians. J Fam Pract.1999;48:264-271.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10229250&dopt=AbstractGoogle Scholar 97. Cole J, Conneally PM, Hodes ME, Merritt AD. Genetic family history questionnaire. J Med Genet.1978;15:10-18.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=633315&dopt=AbstractGoogle Scholar 98. Gilpin CA, Carson N, Hunter AG. A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center. Clin Genet.2000;58:299-308.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11076055&dopt=AbstractGoogle Scholar 99. Gerson R, McGoldrick M. The computerized genogram. Prim Care.1985;12:535-545.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3852342&dopt=AbstractGoogle Scholar 100. Ebell MH, Heaton CJ. Development and evaluation of a computer genogram. J Fam Pract.1988;27:536-538.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3193069&dopt=AbstractGoogle Scholar 101. Westman J, Hampel H, Bradley T. Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment. J Med Genet.2000;37:354-360.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10807694&dopt=AbstractGoogle Scholar 102. Emery J. Computer support for genetic advice in primary care. Br J Gen Pract.1999;49:572-575.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10621995&dopt=AbstractGoogle Scholar 103. Green MJ, Fost N. An interactive computer program for educating and counseling patients about genetic susceptibility to breast cancer. J Cancer Educ.1997;12:204-208.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9440011&dopt=AbstractGoogle Scholar 104. Green MJ, Fost N. Who should provide genetic education prior to gene testing? computers and other methods for improving patient understanding. Genet Test.1997;1:131-136.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10464637&dopt=AbstractGoogle Scholar 105. Rose P, Humm E, Hey K, Jones L, Huson SM. Family history taking and genetic counselling in primary care. Fam Pract.1999;16:78-83.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10321401&dopt=AbstractGoogle Scholar 106. Fletcher SW, Elmore JG. Clinical practice: mammographic screening for breast cancer. N Engl J Med.2003;348:1672-1680.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12711743&dopt=AbstractGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Does This Patient Have a Family History of Cancer?: An Evidence-Based Analysis of the Accuracy of Family Cancer History

JAMA , Volume 292 (12) – Sep 22, 2004

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References (111)

Publisher
American Medical Association
Copyright
Copyright © 2004 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.292.12.1480
Publisher site
See Article on Publisher Site

Abstract

Abstract Context A family history of certain cancers is associated with an increased risk of developing cancer. Both cancer screening and genetic services referral decisions are often based on self-reported pedigree information. Objective To determine the accuracy of self-reported family cancer history information. Data Sources English-language articles were retrieved by searching MEDLINE (1966-June 2004) using Medical Subject Headings family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. Additional articles were identified through bibliography searches. Study Selection Original studies in which investigators validated self-reported family history by reviewing the identified relatives' medical records, death certificate, or cancer registry information were included, as well as studies that evaluated breast, colon, ovarian, endometrial, and prostate cancers. Data Extraction Two of the 3 investigators independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of self-reported family cancer history information. Only data from studies that evaluated both positive and negative family cancer histories were included within the analyses. A total of 14 studies met the search criteria and were included in the review. Data Synthesis For patients without a personal history of cancer, the positive and negative LRs of a family history of the following cancers in a first-degree relative were 23.0 (95% confidence interval [CI], 6.4-81.0) and 0.25 (95% CI, 0.10-0.63) for colon cancer; 8.9 (95% CI, 5.4-15.0) and 0.20 (95% CI, 0.08-0.49) for breast cancer; 14.0 (95% CI, 2.2-83.4) and 0.68 (95% CI, 0.31-1.52) for endometrial cancer; 34.0 (95% CI, 5.7-202.0) and 0.51 (95% CI, 0.13-2.10) for ovarian cancer; and 12.3 (95% CI, 6.5-24.0) and 0.32 (95% CI, 0.18-0.55) for prostate cancer, respectively. Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives. Conclusions Patient-reported family cancer histories for first-degree relatives are accurate and valuable for breast and colon cancer risk assessments. Negative family history reports for ovarian and endometrial cancers are less useful, although the prevalence of these malignancies within families is low. Clinical scenario A 35-year-old woman presents for an initial visit and during the medical interview mentions that her mother and grandmother had breast cancer. She reports that her mother's cancer was diagnosed at age 42 years and she believes that her grandmother, on her mother's side, was diagnosed in her 30s. Because of her family history, she is concerned about her risk of developing breast cancer. Despite having no symptoms of breast cancer, she wonders at what age she should start having mammograms and whether she should have genetic testing. Why is it important to record an accurate family history of cancer? Quiz Ref IDIndividuals with a positive family history for certain kinds of cancers can have an increased risk of developing cancer themselves.1,2 Two meta-analyses found relative risks of 2.1 (95% confidence interval [CI], 2.0-2.2) for breast cancer3 and 3.1 (95% CI, 2.6-3.7) for ovarian cancer4 in women with affected first-degree relatives. Similar higher risks have been noted for endometrial cancer,5-7 colon cancer,7-10 and prostate cancer.11-13 Accurate reporting of family history helps risk stratify patients, which in turn determines screening and prevention interventions. Individuals with family histories that are suggestive of a possible hereditary cancer syndrome (Box 1)14-17 are typically considered at high or very high risk of developing cancer; whereas, individuals with positive family cancer histories for certain cancers but not meeting these specified criteria for hereditary cancer are generally at a moderately increased risk of developing cancer when compared with the general population. Several organizations have recommended initiating screening earlier, more frequently, or both in patients at moderately increased risk of developing cancer based on their family history.18-27 Guidelines have also been published regarding the management of individuals who are at high cancer risk.26,28-30Quiz Ref IDA family history of malignancy will not only influence cancer screening initiation and frequency but also can affect treatment strategies. Family histories affect decisions about cancer chemoprevention31,32 and those individuals identified as being at very high risk may also be considered for risk-reducing surgeries.33 Likewise, algorithms that predict individuals who might be candidates for genetic testing rely almost exclusively on family history information.14,16 Box 1. Examples of Clinical Diagnostic Criteria for 2 Familial Cancer Syndromes and Recommendations Regarding Genetic Testing for Cancer Susceptibility Hereditary Nonpolyposis Colon Cancer (HNPCC)14,15 All of the following criteria should be present: At least 3 relatives must have a cancer associated with HNPCC (colon, endometrial, ovarian, stomach, small bowel, hepatobiliary, ureter, renal-pelvis, brain). One should be a first-degree relative of the other 2. At least 2 successive generations should be affected. At least 1 of the relatives with cancer associated with HNPCC should have received the diagnosis before age 50 years. Hereditary Breast/Ovarian Cancer16* Any of the following criteria should be present: Two breast cancers in a first- or second-degree relative and mean age at diagnosis of 40 years. One breast cancer and 1 ovarian cancer in a first- or second-degree relative and mean age at diagnosis of 41 to 50 years. Two or more breast cancers and 1 ovarian cancer in a first- or second-degree relative. Ovarian cancer in 2 relatives. American Society of Clinical Oncologists Policy Statement on Genetic Testing17 Indications for genetic testing: The individual has personal or family history features suggestive of a genetic cancer susceptibility condition. The test can be adequately interpreted. The results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. *Identified relatives must be on the same side of the family (either maternal or paternal relatives). Because many screening and prevention strategies for cancer rely on self-reported family history information, inaccurate information could potentially result in inappropriate care. A false-negative family cancer history results in an underestimation of cancer risk and missed opportunities for cancer screening. Failure to collect adequate family history information and appropriate management of a patient's cancer risk may result in substandard care and in some cases has resulted in malpractice litigation.34 Conversely, a patient's false belief in a positive family cancer history can cause stress35 and when compounded by the physician's overestimation of risk may lead to unnecessary procedures or surgeries.36 The overestimation of cancer risk based on pedigree data creates unneeded referrals for genetic testing or cancer risk counseling.37,38 The increased availability and demand for genetic services require an even more important role for primary care physicians in recording an accurate family history39,40; however, many physicians lack adequate training in genetics to accurately identify and refer appropriate candidates for genetic services.41,42 Additionally, with direct-to-consumer advertising for genetic testing now a reality,43 accurate family history collection and cancer risk assessment by primary care physicians might help decrease the likelihood of inappropriate referrals for genetic counseling and testing. Few data exist describing how often inaccurate risk assessments are made based on faulty pedigree data. In 1 retrospective study35 that examined patients referred to 2 cancer genetic clinics, patient management was changed in 23 (11%) of 213 patients after their previously reported family history information was found to be inaccurate. In 15 of these patients, screening was thought to be unnecessary, although in 8 patients cancer risk was determined to be greater than initially believed. Further studies have supported these findings, with 1 study44 determining that 6 (5%) of 120 patients referred to a cancer clinic had changes in management after confirmation of the family cancer history revealed discrepancies. In most of these patients, the cancer risk had been overestimated. Prevalence of a Positive Family History of Specific Familial Cancers The prevalence of a family history of cancer varies depending on the cancer type. The prevalence of a family history of breast cancer has been estimated to range from 5% to 22%,45-48 colon cancer 2.0% to 9.4%,8,45,46 ovarian cancer 1.1% to 3.5%,45,46,48 endometrial cancer 0.5% to 1.4%,45,46 and prostate cancer 4.6% to 9.5%.11,13,46,49 Most of this variation is due to methodology and study population. Some studies included distant relatives in the definition of a positive family history, while other studies have focused only on first-degree relatives. Variability in rates also occurs when the results are derived from the general population as opposed to patients referred to cancer or genetic centers, which have higher prevalence rates. How to Elicit a Family History Family history information is important for risk assessment in numerous chronic medical conditions in addition to cancer, such as diabetes mellitus and cardiovascular disease; therefore, eliciting a family cancer history can serve as a model for collecting family history information for other disorders. Typically, family history information is collected directly from the patient or from screening questionnaires filled out by the patient. Alternatively, the patient's parent or another family member may provide the information. Screening questionnaires are often either a list of relatives, with space to provide information on overall health, age, and cause of death, or a list of adult-onset diseases with space to list the affected relative. Disease history should be collected on both first-degree relatives (mother, father, sisters, brothers, children) and second-degree relatives (maternal and paternal grandparents, aunts, uncles, nieces, and nephews). It is important to inquire about various types of cancers as certain hereditary cancer syndromes can be identified by specific cancers that cluster together within families (Box 1), such as endometrial with colon50 and breast with ovarian.51,52 If the initial screening interview or questionnaire reveals a potential familial predisposition to a particular disease, the family history should be expanded. Although establishing the numbers of both affected and unaffected relatives is important for determining penetrance and predicting the likelihood of gene mutations, this information for primary care physicians would seldom influence cancer screening decisions. Quiz Ref IDFor affected relatives, documenting the age at cancer diagnosis is important as patients developing cancer at ages significantly earlier than typically expected increases the possibility of a hereditary cancer syndrome. Inaccurate reporting of ages at diagnosis for breast cancer can have a considerable influence on risk prediction in families with fewer than 4 affected relatives.53 A 3-generation pedigree, displayed graphically in the Figure 1, offers a convenient symbolic method of summarizing information. Because of prior inconsistencies in pedigree symbol usage, the Pedigree Standardization Task Force, organized through the National Society of Genetic Counselors, has proposed recommendations for a standardized pedigree nomenclature.54 When recording a pedigree, particularly for breast and gynecological cancers, it is important to inquire about disease in both maternal and paternal lineages as mutations can be transmitted through either parent. When collecting information on second-degree relatives, it is important to note the lineage to which the relative belongs (such as paternal vs maternal grandparents) as the degree of risk might vary if affected relatives do not belong to the same lineage. A brief reference for physicians on the family medical history has been prepared by the American Medical Association and is available at http://www.ama-assn.org/ama/pub/category/2380.html. For a more detailed account, the authors recommend consulting The Practical Guide to the Genetic Family History by Bennett.55 Family history information can be collected during a patient care visit or outside of the clinical encounter. Methods of collecting family history information outside of the clinical encounter can include paper questionnaires,56 computer questionnaires in kiosks within a clinic waiting area,37 Web-based electronic collection, and interviews by health care professionals. The optimal means of collection has not been determined. Methods Two of the authors (H.J.M. and D.R.S.) performed independent searches of the MEDLINE database for English-language articles dated 1966 to June 2004 from the PubMed search engine. The following Medical Subject Headings were used: family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. We also searched using textwords accuracy, sensitivity, specificity, and family history combined with the conditions breast cancer, colon cancer, ovarian cancer, prostate cancer, endometrial cancer, or uterine cancer. We specifically included cancers that were likely to be commonly encountered by primary care physicians and whose management might be altered based on family history information. The reviewers evaluated article abstracts and chose studies for full-text review based on the abstract. We searched the bibliographies of all retrieved articles to identify additional sources. Articles were included if they were original articles describing the accuracy of the site-specific family history for the prespecified cancers and contained a criterion standard. Studies presenting aggregate data (all cancer types combined into a single measure) for self-reported family cancer history information were excluded. For purposes of this study, the criterion standard for a positive family history of cancer required verification from the identified relative's medical record, physician, or death certificate, and/or verification within a population cancer registry. For studies to be included in our analysis, verification of a negative family history for cancer had to have been performed. Thus, if a study participant reported that a relative had no history of breast cancer, the relative's medical records, death certificate, if applicable, or local cancer registry were examined for verification of this report. The completeness of case-findings within tumor registries varied, with 83% to 99% of cancers identified through medical record reviews and patient interviews also being present within the registry.57-61 Specific cancer sites are correctly recorded within the registry in 93% to 97% of cases. Forty-nine percent of discrepancies within tumor registries result from changes in an initial diagnosis with a failure to update registry information.61 For breast cancer, the sensitivity and specificity of tumor registries are high.62 Other tumors listed within registries have similar high sensitivities.63,64 The National Program of Cancer Registries of the Centers for Disease Control and Prevention has created a system that provides the rationale for accepting these data in studies that attempt validation of the patient's family history.65 Although death certificates probably lack the accuracy of tumor registries, the poorer performance of death certificates is more likely attributed to poor sensitivity (the death certificates do not record the information when in fact the decedent had cancer).66 Based on autopsy studies, the death certificate is estimated to have a sensitivity of 87% for identifying cancer.67 We identified 22 studies from our search using the listed criteria.44,68-88 Of these, only 7 provided information on both the test characteristics of a positive and negative report of a family history.71,73,74,76,78-80 One study specifically assessed pedigrees suggestive of hereditary nonpolyposis colorectal cancer (HNPCC)76 and was included within the analysis. Sensitivity and specificity were determined for the family history interview for HNPCC but this information was not combined with other colon cancer studies. We used techniques described from previous "Rational Clinical Examination" articles to determine study quality and all 7 evaluated studies were assigned a quality score of C,89 which reflects a study with an independent blind comparison of sign or symptom and a criterion standard of diagnosis among nonconsecutive patients suspected of having the target condition. Because the population studied could influence reporting accuracy, test characteristics were calculated separately for individuals with a personal history of cancer as well as individuals without a personal history of cancer. Sensitivity and specificity of patient self-report of a family history of cancer and likelihood ratios (LRs) of a positive or negative report were calculated based on raw data supplied by the original articles that met our search criteria. Confidence intervals for LRs were computed using previously described methods.90 We used random effects summary measures for combining the data because this provided a broad range of possible data that display the uncertainty around the point estimates. The summary measures described this uncertainty better than the simple range of possible data from the original studies. For colon cancer, 1 study76 was not included within the summary LRs because it specifically evaluated the family history for HNPCC rather than colon cancer in general. Results Precision Precision reflects the reproducibility of a measurement. Assessing the precision of the family history interview is challenging as it can be influenced by both patient and physician factors. Although we were unable to identify any studies assessing health care physician interrater or intrarater reliability for the family history assessment, 1 study91 in breast cancer examined the reliability of patient self-report. In this nested case-control study,91 comparisons were made between self-reported family history information in women before the development of the disease and after the development of the disease. Follow-up surveys were completed 2 years after the initial survey. Both women who had developed breast cancer and women who had not developed breast cancer were surveyed. The agreement for maternal history of breast cancer was κ = 0.92 and κ = 1.00 for cases and controls, respectively; and for a history of breast cancer in a sister, κ = 0.65 and κ = 0.88, respectively. Although the study did not assess whether a real change in family history might have occurred during the study period, these results suggest that self-reported family breast cancer history is probably only slightly influenced by recall bias. Patient precision regarding the family history interview for other cancers has not been reported. Accuracy Accuracy represents how well a particular test measures the value it is intending to measure. Seven studies concerning family history were ultimately included in this analysis (Table 1).71,73,74,76,78-80 Three studies collected family history from personal patient interviews,73,74,79 while the other 4 relied on a self-completed survey.71,76,78,80 Four studies solely relied on cancer registry data as their criterion standard73,74,79,80; 2 studies used a combination of medical records and death certificates,71,78 while the remaining study used all 3 sources as its criterion standard.76 Only information for first-degree relatives was extracted. For individuals affected with cancer (Table 2), the positive and negative LR of a self-reported family cancer history in a first-degree relative were 23.0 (95% CI, 8.1-64.0) and 0.29 (95% CI, 0.13-0.67) for colon; 41 (95% CI, 23-75) and 0.07 (95% CI, 0.03-0.13) for breast; 20.0 (95% CI, 4.3-89.0) and 0.55 (95% CI, 0.35-0.86) for endometrial; 44 (95% CI, 15-132) and 0.21 (95% CI, 0.12-0.37) for ovarian; and 24.0 (95% CI, 2.3-262.0) and 0.25 (95% CI, 0.16-0.39) for prostate cancers, respectively. For patients without a personal history of cancer (Table 3), the positive and negative LRs of a family history for the following cancers in a first-degree relative were 23.0 (95% CI, 6.4-81.0) and 0.25 (95% CI, 0.10-0.63) for colon; 8.9 (95% CI, 5.4-15.0) and 0.20 (95% CI, 0.08-0.49) for breast; 14.0 (95% CI, 2.2-83.4) and 0.68 (95% CI, 0.31-1.52) for endometrial; 34.0 (95% CI, 5.7-202.0) and 0.51 (95% CI, 0.13-2.10) for ovarian; and 12.3 (95% CI, 6.5-24.0) and 0.32 (95% CI, 0.18-0.55) for prostate cancers, respectively. The estimates for sensitivity, specificity, and LRs for unaffected individuals for prostate, breast, endometrial, and ovarian cancers are based on data from a single study by Kerber and Slattery.74 Of the remaining 15 studies, we excluded 8 studies81-88 because the tumor data were presented in aggregate (ie, family history of any cancer) or were unclear; therefore, we were unable to extrapolate site-specific numbers. Seven studies evaluated only the positive predictive value of self-reported family history information for breast, colon, ovarian, prostate, and endometrial cancers (Table 4). Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives. Individuals with personal histories of cancer tended to report family histories with a greater positive predictive value, although the number of studies evaluating unaffected individuals was limited. Common Reasons for False-Positive or False-Negative Reports In cancers in which patients are likely to be accurate in their report, such as breast cancer, case reports have indicated that false-positive reports are associated with malingering, problems with patient-physician communication, or prior history of benign breast disease being reported as malignant.36 Other common reasons for false-positive reports of family cancer history result from confusion based on primary vs metastatic disease.68,92 This confusion has been described with false reports of primary liver cancer as well as central nervous system cancers. Cancers that are frequently overreported include melanoma, which is incorrectly reported in almost half of reports,93 and non–colonic gastrointestinal malignancies.35 Quiz Ref IDSeveral factors relate to a false-negative report of a family history of cancer. In 1 study,94 older patients and non–white respondents were more likely to underreport a family history of cancer. Another study74 demonstrated that older patients were more likely to falsely report a negative family history of cancer, while patient sex and education level have little effect on the accuracy of reporting. Specific cancers with high rates of false-negative reporting include central nervous system tumors and hematological malignancies.94 Other Means for Collecting Family History Information and Ways to Improve Family History Data Collection Several barriers exist for the collection of family history information. Patient specific factors that might result in poor pedigree collection include poor family communication, family myths, or individual spiritual beliefs. For physicians, probably the most significant barrier is time. Although a comprehensive family history assessment can take 15 to 30 minutes,95 the average primary care visit lasts only 16 minutes.96 Several alternative methods that involve collecting this information outside the context of the clinical visit may facilitate the collection of family history information. These other methods include self-completed patient paper surveys, computer-based tools, and personal visits arranged solely for pedigree collection. Family history questionnaires offered outside of a clinical visit confer several theoretical advantages to visit-based pedigree assessment.97 Besides saving clinic time, patients can consult with family members to check the accuracy of the information, which can then be reviewed and integrated into a clinic appointment when relevant. The data from a questionnaire developed in Switzerland compared with information found within 2 population-based cancer registries exhibited sensitivities of 74% and 85% and specificities of 97%.56 Family history assessment tools (Box 2) have also been developed to assist physicians in determining which individuals might be candidates for genetic testing.98 Box 2. Selected Web Sites for Cancer Risk Calculators Methods for Estimating Cancer Risk Various cancer sites: http://www.yourcancerrisk.harvard.edu Breast Cancer Risk Assessment tools: http://bcra.nci.nih.gov/brc/start.htm; http://www.halls.md/breast/risk.htm Methods for Estimating the Likelihood of aBRCAMutation BRCAPRO statistical model: http://www3.utsouthwestern.edu/cancergene/ Mutation prevalence tables: http://www.myriadtests.com/provider/mutprev.htm Computerized genograms can also be effective and convenient tools for both patients and physicians.99-101 These tools offer the benefits of paper-based systems and, through clinical decision support, educate patients and offer guidance to physicians.102-104 Sweet et al37 compared family history information obtained by physicians at a comprehensive cancer clinic with those directly entered by patients into a computer program. Patients were then determined to be "high risk" for cancer based on pedigree information collected from either the computer program or information recorded within the medical record. Of 362 computer entries, 69% had some form of family history information recorded within their medical record. A total of 101 patients were considered high-risk based on their pedigree information collected from the computer program but only 69 of these patients had information recorded within their medical record to confirm this high risk. Special visits outside of the clinical encounter have also been evaluated as a means to obtain family history information. In 1 study,105 patients observed at a single primary care practice were invited to a special visit designed to collect detailed family history information. Ten percent of patients observed in the pedigree clinic had a family history of cancer (breast, colon, melanoma, or thyroid) and some patients were referred for further care based on their pedigree. Patients were less anxious about their family history after the special visit, but this effect was not sustained beyond 12 weeks. A major limitation of the study was the poor attendance to the special clinic; only 16% of invited patients attended. Scenario resolution This patient's pretest probability of having a positive family history of breast cancer before her clinical interview can be estimated at 22%.48 After considering her self-reported pedigree, her posttest probability for a family history of breast cancer increased to 71% (95% CI, 60%-81%) (Table 5). Based on the family history information presented, it is likely that this woman does in fact have a positive family history for breast cancer and that seeking confirmatory evidence is unlikely to offer any additional gain. This patient has 2 relatives affected with breast cancer, both diagnosed before 50 years and 1 a first-degree relative. Using online mutation prevalence tables (Box 2), this woman's risk estimate of harboring a deleterious mutation for either BRCA1 or BRCA2 was 10% and a referral was recommended to a specialized cancer risk assessment program for counseling on genetic testing.106 During pretesting counseling, she learned of the potential limitations of testing on a presymptomatic individual without a known deleterious mutation. The genetic counselor suggested testing 1 of her affected relatives first to produce a more informative test. The patient noted that her maternal grandmother is no longer alive and she is not particularly close to her mother and unsure if her mother would be willing to undergo testing. After pretesting genetic counseling, the patient decided not to be tested for a BRCA1 or BRCA2 mutation and plans to broach the subject of testing with her mother. 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Journal

JAMAAmerican Medical Association

Published: Sep 22, 2004

Keywords: cancer,family history,genetic pedigree,breast cancer,breast

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