Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic tests

Pujol, Pascal; Lyonnet, Dominique Stoppa; Frébourg, Thierry; Blin, Joël; Picot, Marie‐Christine; Lasset, Christine; Dugast, Catherine; Berthet, Pascaline; Paillerets, Brigitte Bressac-de; Sobol, H.; Grandjouan, S.; Soubrier, Florent; Bruno, Benedetto; Guimbaud, Rosine; Lidereau, Rosette; Jonveaux, Philippe; Houdayer, Claude; Giraud, Sophie; Olschwang, Sylviane; Nogué, Erika; Galibert, Virginie; Bara, Csilla Iuliana; Nowak, Frédérique; Khayat, D.; Noguès, Catherine

doi:10.1007/s10549-013-2669-9

Cited by 35 publications

(47 citation statements)

References 36 publications

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“…A recent survey in the United States revealed that only 19% of primary care physicians accurately assessed family history for BRCA1/BRCA2 testing (25). In BRCA1/ BRCA2 families in France, most eligible relatives are not referred for testing (26). In the present study in Israel, only 35% (29 of 82) of high-cancer-incidence families had been referred previously for genetic counseling, despite its availability within the Israeli universal single-payer health care system.…”

Section: Discussioncontrasting

confidence: 58%

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

Gabai-Kapara

Lahad

Kaufman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

318

275

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In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingooophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations. genomics I nherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Among female mutation carriers, presymptomatic surgical measures significantly reduce morbidity and mortality (1, 2). In particular, risk-reducing salpingo-oophorectomy (i.e., the removal of ovaries and fallopian tubes from a woman without ovarian cancer) reduces risk both of breast cancer and of ovarian cancer, as well as overall mortality (1). However, for many mutation carriers identified following their first cancer diagnosis, genetic testing was not previously indicated because family history did not suggest inherited cancer predisposition (3)(4)(5)6). From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.Among Ashkenazi (European) Jews (AJ), three mutations, BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, account for the great majority of inherited cancer risk due to BRCA1 and BRCA2 (7). In the AJ population, 2.5% of persons carry one of these three mutations (8), and the mutations account for 11% of breast cancer (3) and 40% of ovarian cancer (9, 10). These observations suggest that genetic testing in the AJ population for these mutations fulfills WHO criteria for population screening (11, 12): The disease is an important public health burden to the target popu...

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Section: Discussioncontrasting

confidence: 58%

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

Gabai-Kapara

Lahad

Kaufman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

318

275

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“…Breast, ovarian and colorectal cancer referrals made up over 90% of cancer in a descriptive study of referrals to cancer genetics services in the UK 26 with a figure of 82.2% in a similar analysis of French services. 27 In both reports, breast and bowel cancer accounted for around 60% and 20% of referrals, respectively. Breast, colorectal and NMSC were among the five most frequent tumours, an observation that is also seen in the UK population.…”

Section: Discussionmentioning

confidence: 95%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

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Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n ¼ 62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.

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“…In addition, there may be differences in rates of referral depending on the syndrome itself or the organ primarily affected by the syndrome. Previous studies assessing other hereditary cancer syndromes have suggested under-referral for Lynch syndrome genetic counseling versus BRCA1/2 genetic testing in patients with gynecologic cancer (20). Additionally, the uptake of genetic counseling has been shown to be lower in patients with EC versus those with ovarian cancer (21).…”

Section: Discussionmentioning

confidence: 99%

Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome

Batte

Bruegl

Daniels

et al. 2014

Gynecologic Oncology

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Objective Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. Methods The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6, or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. Results In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome. 42% were seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome. 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel, and limited insurance coverage. Conclusions There are several barriers to genetic counseling and testing follow up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

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Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic tests

Cited by 35 publications

References 36 publications

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome

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