Preventing ovarian cancer through genetic testing: a population‐based study

Finch, Amy; Bacopulos, Stephanie; Rosen, Barry P.; Fan, Isabel; Bradley, Linda; Risch, Harvey A.; McLaughlin, John; Lerner‐Ellis, Jordan; Narod, Steven A.

doi:10.1111/cge.12313

Cited by 18 publications

(18 citation statements)

References 7 publications

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“…By testing healthy relatives of ovarian cancer patients identified to carry a BRCA1 or BRCA2 mutation, the incidence of breast/ovarian cancer in the family can be reduced. However, we have estimated that only 4% of ovarian cancer cases in Ontario are potentially preventable through genetic testing under current guidelines [40]. For RAD51C, the preventable fraction under the current paradigm would be far less.…”

Section: Who Should Be Tested?mentioning

confidence: 98%

Genetic testing for RAD51C mutations: in the clinic and community

2015

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Much of the observed familial clustering of breast and ovarian cancer cannot be explained by mutations in BRCA1 and BRCA2. Several other cancer susceptibility genes have been identified, but their value in routine clinical genetic testing is still unclear. Germline mutations in RAD51C have been identified in about 1% of hereditary breast and ovarian cancer families. RAD51C mutations are predominantly found in families with a history of ovarian cancer and are rare in families with a history of breast cancer alone. RAD51C is primarily an ovarian cancer susceptibility gene. A mutation is present in approximately 1% of unselected ovarian cancers. Among mutation carriers, the lifetime risk of ovarian cancer is approximately 9%. The average age at onset is approximately 60 years; this suggests that preventive oophorectomy can be delayed until after natural menopause. Under current guidelines, genetic testing for RAD51C is expected to have a limited impact on ovarian cancer incidence at a population level. This is because the penetrance is 9% to age 80; the great majority of families with mutations would be represented by a single case of ovarian cancer, these are potentially preventable through population screening but not through screening of established ovarian cancer families.

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Section: Who Should Be Tested?mentioning

confidence: 98%

Genetic testing for RAD51C mutations: in the clinic and community

2015

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“…■ First, a significant proportion of BRCA mutation carriers do not reach the 10% threshold; they therefore represent missed opportunities for identification 12 . ■ Very few patients with prostate cancer or pancreatic cancer are being tested.…”

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confidence: 99%

“…■ Very few patients with prostate cancer or pancreatic cancer are being tested. In addition, many individuals who do qualify for genetic testing fail to be identified and referred by their health care provider 12 . Many physicians do not take an adequate family history and might not be well-apprised of the criteria for testing or of the referral process.…”

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confidence: 99%

Coming of Age in Canada: A Study of Population-Based Genetic Testing for Breast and Ovarian Cancer

2017

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The BRCA1 and BRCA2 genes are the two most commonly mutated in hereditary breast and ovarian cancer, and they are the canonical pair when it comes to cancer testing 1 . There are many other candidate genes, and large-panel testing is increasingly the norm even though not all practitioners are in agreement 2 that testing for 20 genes is better than testing for 2. Mutations are associated with lifetime risks of 80% for breast cancer and 15%-40% for cancer of the ovary or fallopian tube for BRCA2 and BRCA1 respectively 3 . BRCA2 is the most frequently mutated gene in both prostate cancer 4,5 and pancreatic cancer [6][7][8] , and patients with BRCA2 mutations can benefit from novel therapies such as cis-platinum 9 . Annually, about 8500 cases of prostate cancer and 2150 cases of pancreatic cancer are diagnosed in Ontario, but very few of those patients are being tested for BRCA2.Genetic screening is now mainstream as a consequence of diminished sequencing costs, increased public awareness, celebrity endorsement, and the now wide availability to women of preventive surgery through public and private health insurance. Intensified screening for mutation carriers with annual magnetic resonance imaging is advocated and is increasingly available 10 . Additionally, women with hereditary breast cancer can benefit from personalized treatment (both surgical and medical), which might include bilateral mastectomy, salpingo-oophorectomy, and tailored chemotherapy (cis-platinum or olaparib) 11 .The current model of delivering genetic testing for the BRCA genes in North America dates to the mid-1990s, at a time when genetic testing was expensive and the clinical benefits were largely unproven. Because of the high cost, public and private insurers were not willing to pay for testing for all comers. In the resulting model, a women is referred by her physician to a specialized cancer genetics clinic, where a formal assessment is conducted. If the risk estimate for carrying a mutation exceeds a threshold value (usually 10%), then genetic testing for the BRCA genes ensues. If not, then the woman is reassured and sent off with a number of recommendations based on her personal and family history of cancer. In many clinics, the volume of patient requests now exceeds the number of available appointments, and triage is conducted by mail or telephone. The genetics counsellor serves two purposes: informing women about cancer risk, management options, and the testing process; and ensuring that testing is rationed first to the women who are the most suitable candidates.We believe that the current model is outdated, and here we propose an alternative model based on direct-toconsumer population-based testing. The reasons are these:■ First, a significant proportion of BRCA mutation carriers do not reach the 10% threshold; they therefore represent missed opportunities for identification 12 . ■ Very few patients with prostate cancer or pancreatic cancer are being tested. In addition, many individuals who do qualify for genetic testing fail to be ide...

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“…However, at present, few women who carry a mutation are identified before they develop ovarian cancer and few are given an opportunity for prevention. Despite the fact that genetic testing for BRCA1 and BRCA2 has been available since 1995, under the current testing protocol in Ontario, fewer than 4% of all ovarian cancers are potentially preventable (of a possible 13%) [18]. Realistically, only 1% of ovarian cancers are prevented [18].…”

Section: Genetic Testing: High-risk Womenmentioning

confidence: 99%

“…Despite the fact that genetic testing for BRCA1 and BRCA2 has been available since 1995, under the current testing protocol in Ontario, fewer than 4% of all ovarian cancers are potentially preventable (of a possible 13%) [18]. Realistically, only 1% of ovarian cancers are prevented [18]. Achieving maximum impact will require population-based genetic testing to identify women at high risk of ovarian cancer, followed by a recommendation for prophylactic bilateral salpingo-oophorectomy.…”

Section: Genetic Testing: High-risk Womenmentioning

confidence: 99%