Out of 3,765 ovarian cancer patients, 2,793 (74.2%) were treated at an outside institution for ovarian cancer care before presentation to our institution. Individuals who were diagnosed with a BRCA1 or BRCA2 mutation before their initial visit to our institution were included in the analysis as a successful referral. In total over the 9-year study period, 276 of 896 patients (30.8%) who met substantial risk (more than 20–25% chance of having a BRCA1 or BRCA2 mutation) criteria were referred for genetic counseling. Of those 276, 92 (33.3%) patients presented as new patients to our institution having been previously referred for genetic counseling.
In a multivariate analysis performed to predict which patients were referred out of the subset of patients who met criteria for being at substantial risk (more than 20–25% chance of having a BRCA1 or BRCA2 mutation), personal history of breast cancer, positive family history of either premenopausal breast or ovarian cancer at any age, and Jewish religion were associated with an increased odds of referral (Table 3). Other variables with a significantly increased odds of referral include year of initial visit, age at first visit and grade 3 disease.
There was a statistically significant difference in patient type and race between ovarian cancer patients meeting substantial risk who were referred and not referred. Newly diagnosed patients were more often referred for genetic counseling than new patients who presented with recurrent disease or patients seen for a second opinion (P<.001) (Fig. 3). Ovarian cancer patients who transferred their care with recurrent disease were 56% less likely to be referred than women who were being seen with newly diagnosed disease. Those patients with recurrent disease who were seen for a second opinion were 77% less likely to be referred (Table 3). African-American women with ovarian cancer who met substantial risk criteria were less likely to be referred for genetic counseling than white women (OR 0.25, 95% CI 0.09–0.70) (Table 3).
During the 9-year time period, 242 ovarian cancer patients from this cohort were seen for genetic counseling. Of those, 208 chose to undergo germline DNA testing for BRCA1 and BRCA2 mutations. Of the women who underwent genetic testing, 102 (49%) were found to have a deleterious mutation, 78 with a BRCA1 mutation and 24 with a BRCA2 mutation.
Our study suggests that physicians are missing important opportunities to identify ovarian cancer patients with germline BRCA1 and BRCA2 mutations. Interestingly, we found that health care providers were dictating family history in the initial history and physical in a large majority of patients, and there was agreement between the dictated family history and the self-reported questionnaire. However, referral of those high-risk patients to genetic counseling was poor in 1999, and, although improved in 2007, was still below 50%. In addition, we found that African-American women with ovarian cancer who met the substantial risk criteria were less likely to be referred for genetic counseling than white or Hispanic women.
The first step to improving the delivery of health care is to understand and define the deficit. Although this analysis is limited in that it is a single institution study, more than half of the patients were seen elsewhere before being seen as new patients at our tertiary care cancer center. Given the availability of cancer genetics at a tertiary care cancer center, we believe that it is possible that the incidence of referral is even lower in a community setting.
At our institution, the process by which cancer genetic counseling services are provided has evolved. During this study period, we did not have a systematic method for identifying those ovarian cancer patients with high-risk criteria. Individual clinicians had different practice patterns for referring patients to genetic counseling. This lack of a systematic approach likely resulted in our low incidence of referral. However in 2006, genetic counselors were integrated into the gynecology department. Now patients are seen for genetic counseling appointments in the same clinic space where they receive their routine oncology care. Appointments are coordinated with other clinic visits and counselors are available for urgent consults in the outpatient and inpatient setting.
As the medical literature has evolved over the past 10 years, physicians have become more aware of the prevalence of BRCA mutations in ovarian cancer patients. This awareness has likely led to an increased number of referrals. Published guidelines from groups such as the American College of Obstetricians and Gynecologists have been developed which outline criteria for hereditary cancer risk assessment and genetic testing for germline BRCA1 and BRCA2 mutations.13–15 In addition, patients and family members may be requesting BRCA testing more frequently as there has been increased coverage of BRCA mutation testing by the lay press. However, even in recent years our incidence of referral for substantial risk patients has been surprisingly low.
It is not clear when is the best time to refer ovarian cancer patients to genetic counseling. Family history and past medical history are routinely obtained at the initial visit and may not be reviewed during future focused visits. A discussion regarding the need for genetic counseling is rarely an emergency and is thus, often postponed and then overlooked. Our findings suggest that cancer patients at increased risk for a hereditary cancer syndrome were less likely to be referred as time elapsed after their first visit. Patients seen as new patients in the setting of recurrent disease or for second opinions were also less likely to be referred than patients presenting with a new diagnosis of ovarian cancer. We believe that this may be a result of the physician having a more focused approach to those patients and not integrating the family or personal past medical history in the same way as they would with a newly diagnosed ovarian cancer patient. Regardless of when each practice or physician chooses to screen patients for risk of hereditary cancer syndromes, it is most likely to be successful if performed in a systematic fashion.
Evidence suggests that those who already have cancer may be more willing to have genetic testing.24 The traditional barriers to genetic counseling such as financial concerns17,24,25,26 and the fear of genetic discrimination17,27,28 may be decreased when cancer patients are tested. In addition, testing the cancer patient for a germline BRCA mutation is more likely to be covered by insurance.29 Finally, the fear of genetic discrimination may be less of an issue in individuals with cancer as their diagnosis trumps any theoretical predictive risk implied by a germline mutation. Indeed, one recent study found that 89% of ovarian cancer patients would be willing to have genetic testing for BRCA mutations if it would directly affect their cancer therapy and 87% would be willing even if it was solely to benefit family members.30
How many ovarian cancer patients attend genetic counseling after referral, how many decide to undergo testing for germline BRCA1 and BRCA2 mutations, and then ultimately, how many test positive for mutations were not the primary aim of this current analysis. In this study we chose to focus on the physician's role of identifying which patients fulfill published guidelines for hereditary cancer risk assessment as it is the first step in the process and is the only step that is under the full and direct control of the health-care provider. Improving the number of appropriate referrals is an important aspect of cancer prevention efforts. Indeed, 49% of ovarian cancer patients who chose to undergo testing were found to have a deleterious mutation in BRCA1 or BRCA2. This high incidence of positive tests suggests that applying published guidelines such as the American College of Obstetricians and Gynecologists Practice Bulletin on Hereditary Breast and Ovarian Cancer syndrome15 to clinical practice can successfully focus genetic testing efforts in a high-risk population.
In conclusion, failure to identify cancer patients who have an inherited cancer predisposition has many important implications, and standardized interventions are clearly needed to improve the incidence of appropriate referrals of cancer patients at risk for hereditary cancers who may benefit from genetic testing. Given the current and future therapeutic implications, greater attention to developing a systematic process of identifying cancer patients with hereditary cancer syndromes is needed. At-risk individuals should be referred to genetic counseling as an integrated, routine aspect of care. Although physicians traditionally have focused their clinical efforts on cancer therapy, they also have a crucial role in cancer prevention through the identification of individuals with hereditary cancer syndromes.
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Figure. No caption available.