BRCA1/2 testing in newly diagnosed breast and ovarian cancer patients without prior genetic counselling: the DNA-BONus study

Abstract

Germline BRCA1/2 testing of breast and ovarian cancer patients is growing rapidly as the result affects both treatment and cancer prevention in patients and relatives. Through the DNA-BONus study we offered BRCA1/2 testing and familial risk assessment to all new patients with breast (N = 893) or ovarian (N = 122) cancer diagnosed between September 2012 and April 2015, irrespective of family history or age, and without prior face-to-face genetic counselling. BRCA1/2 testing was accepted by 405 (45.4%) and 83 (68.0%) of the patients with breast or ovarian cancer, respectively. A pathogenic BRCA1/2 variant was found in 7 (1.7%) of the breast cancer patients and 19 (22.3%) of the ovarian cancer patients. In retrospect, all BRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2 testing. Hospital Anxiety and Depression Scale (HADS) scores showed that the mean levels of anxiety and depression were comparable to those reported for breast and gynecological cancer patients in general, with a significant drop in anxiety symptoms during a 6-month follow-up period, during which the test result was forwarded to the patients. These results show that BRCA1/2 testing is well accepted in newly diagnosed breast and ovarian cancer patients. Current test criteria based on age and family history are sufficient to identify most BRCA1/2 mutation carriers among breast cancer patients. We recommend germline BRCA1/2 testing in all patients with epithelial ovarian cancer because of the high prevalence of pathogenic BRCA1/2 variants. INTRODUCTIONBreast cancer is by far the most common cancer in women worldwide, with more than 1.6 million new cases diagnosed each year. Ovarian cancer is substantially less common, with ∼ 240 000 new cases each year, but with higher mortality. 1 Most cases of breast and ovarian cancer are sporadic, but a minor fraction (2-8% and 8-15%, respectively) is caused by inheritance of pathogenic germline variants in BRCA1 or BRCA2, with variation in prevalence and relative contribution of BRCA1 and BRCA2 in different populations. [2][3][4][5][6][7][8] It is important to identify these patients because the presence of such germline variants affects treatment, follow-up and further cancer prevention in patients with breast or ovarian cancer. 9,10 In addition, it may strongly influence upon their close relatives, as BRCA1/2 testing can identify healthy BRCA1/2 mutation carriers at high risk and thereby prevent cancer and cancer-related deaths through increased surveillance and prophylactic surgery. [10][11][12][13][14][15][16] The most common current practice of BRCA1/2 testing is based on referral of suspected high-risk patients to clinical genetics services for specialized face-to-face genetic counselling. This procedure traditionally includes collection and confirmation of family history, risk

New paradigms forBRCA1/BRCA2testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

“…These findings are therefore likely to be widely applicable, and similar new approaches have been trialled in other countries, such as Norway7 and the Netherlands 27. Even though overall numbers tested are relatively small, the participation rate was high and the mutation yield is consistent with those reported in other studies in heterogeneous populations lacking founder mutations.…”

“…At present there is no proven clinical screening for EOC 2 and unaffected women with completed families who carry BRCA1/BRCA2 mutations typically elect to have a prophylactic bilateral salpingooophorectomy that reduces the risk of EOC by 80-96%. [3][4][5] The prevalence of BRCA1/BRCA2 mutations in unselected women with ovarian cancers ranges from 8% to 22%, [6][7][8][9][10] and this variation can in part be explained by the presence or absence of founder mutations in the study populations. In one study of 1342 unselected patients with invasive ovarian cancer, 161 BRCA1/BRCA2 carriers were identified in 1038 women diagnosed with high-grade serous or endometrioid ovarian cancer (overall frequency 15.5%), confirming that inherited mutations in these genes account for a significant minority of all ovarian cancer cases.…”

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap

“…The majority of patients (59%) chose the DNA-Direct model, of whom 100% completed genetic testing and 89% stated they would choose the DNA-Direct model again 46. A similar ‘DNA BONus’ model in Norway offered genetic testing to all newly diagnosed patients with breast and ovarian cancer using an information sheet in lieu of pre-test genetic counselling, with 68% of patients with ovarian cancer accepting genetic testing 39. Variations of these mainstreamed genetic testing models have been adopted by hospitals in several Canadian provinces and studies are ongoing to evaluate the effectiveness and acceptability of this process in Canada.…”

BRCA1/2 germline testing in non-mucinous epithelial ovarian carcinoma: changing international practice and implications for service provision

“…Hoberg-Vetti et al, 9 in EJHG September 2015, detailed the high acceptability of germline mutation status testing to patients, and further recommended germline BRCA1/2 testing in all patients with epithelial ovarian cancer owing to the high prevalence of pathogenic BRCA1/2 variants in this group.…”