domingo, 13 de septiembre de 2015

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

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


European Journal of Human Genetics advance online publication 9 September 2015; doi: 10.1038/ejhg.2015.196

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

Hildegunn Høberg-Vetti1,2, Cathrine Bjorvatn1,2,3, Bent E Fiane4, Turid Aas5, Kathrine Woie6, Helge Espelid7, Tone Rusken8, Hans Petter Eikesdal3,9, Wenche Listøl1,2, Marianne T Haavind1, Per M Knappskog2,3, Bjørn Ivar Haukanes2, Vidar M Steen1,2,3,11 and Nicoline Hoogerbrugge1,10,11
  1. 1Western Norway Familial Cancer Center, Haukeland University Hospital, Bergen, Norway
  2. 2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
  3. 3Department of Clinical Science, University of Bergen, Bergen, Norway
  4. 4Department of Gynecology and Obstetrics, Stavanger University Hospital, Stavanger, Norway
  5. 5Department of Surgery, Haukeland University Hospital, Bergen, Norway
  6. 6Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
  7. 7Department of Surgery, Haugesund Hospital, Haugesund, Norway
  8. 8Department of Surgery, Førde Central Hospital, Førde, Norway
  9. 9Department of Oncology, Haukeland University Hospital, Bergen, Norway
  10. 10Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
Correspondence: Dr H Høberg-Vetti, Western Norway Familial Cancer Center, Haukeland University Hospital, N-5021 Bergen, Norway. Tel: +47 5 5975475; Fax: +47 5 5977878;
11These authors contributed equally to this work.
Received 2 April 2015; Revised 7 July 2015; Accepted 4 August 2015
Advance online publication 9 September 2015


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 BRCA1/2testing 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, allBRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2testing. 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.


Breast 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 ~240000 new cases each year, but with higher mortality.1Most 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.2345678 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.910 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.10111213141516
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 assessment and eventually BRCA1/2 testing followed by a post-test counselling with dissemination of test results and advice concerning surveillance and follow-up.171819 Based on family history,BRCA1/2-negative families with increased risk of familial breast cancer can also be identified.1820
However, this traditional approach is time consuming and resource demanding for both the patient and the health-care system, with an inherent risk of focusing too much on healthy relatives and not reaching all the cancer patients in question. Moreover, the discovery that BRCA1/2 status can inform treatment decisions in breast and ovarian cancer patients has led to an increased demand for BRCA1/2 testing at the time of cancer diagnosis.921 New approaches toBRCA1/2 testing and genetic counselling may be needed to meet this situation. The aim of this project was therefore to assess the feasibility and impact of offering BRCA1/2 testing to all newly diagnosed patients with breast or ovarian cancer without prior face-to-face genetic counselling. We here report the uptake of BRCA1/2 testing, the incidence of pathogenic BRCA1/2 variants and the individual risk profiles among these unselected breast and ovarian cancer patients. As the psychosocial impact of such BRCA1/2 testing in newly diagnosed cancer patients without prior genetic counselling is scarcely described,22 we also examined the symptoms of anxiety and depression at inclusion and during the follow-up period of 6 months.

Patients and methods

Recruitment of patients

The patients were recruited from four hospitals in Western Norway (Haukeland University Hospital, Stavanger University Hospital, Haugesund Hospital and Førde Central Hospital), including three surgical departments and two gynecological departments, from September 2012 to April 2015. All patients with newly diagnosed breast or ovarian cancer were invited to participate in the study (for overview, see Figure 1). The patients received written information on the project and general information on hereditary breast and ovarian cancer, including the mode of inheritance and the potential consequences of a positive test results; such as the elevated cancer risk, recommended follow-up and risk-reducing strategies for the patient and healthy relatives. They were also informed that a positive test result could affect the surgical treatment of breast cancer patients, whereas specific information on novel therapies, like PARP-inhibitors, was not given. In addition, the patients had the opportunity to contact a genetic counselor on telephone for any further questions. All participants signed informed consent and filled in a structured questionnaire on personal and family medical history. The patients could choose BRCA1/2 testing with or without participating in an associated study of psychosocial aspects (see below). A blood sample was then collected at the local hospital and sent to a central laboratory for BRCA1/2analysis. The study protocol was approved by the Regional Committee for Medical and Health Research Ethics (reference number REK Vest 2012-60).

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