Background Identification of families at risk for ovarian cancer offers the
opportunity to consider prophylactic surgery thus reducing ovarian cancer
mortality. So far, identification of potentially affected families in Germany
was solely performed via family history and numbers of affected family members
with breast or ovarian cancer. However, neither the prevalence of deleterious
variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family
history as trigger for genetic counselling has ever been evaluated. Methods
Prospective counseling and germline testing of consecutive patients with
primary diagnosis or with platinum-sensitive relapse of an invasive epithelial
ovarian cancer. Testing included 25 candidate and established risk genes.
Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2,
MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53) were defined as
established cancer risk genes. A positive family history was defined as at
least one relative with breast cancer or ovarian cancer or breast cancer in
personal history. Results In total, we analyzed 523 patients: 281 patients
with primary diagnosis of ovarian cancer and 242 patients with relapsed
disease. Median age at primary diagnosis was 58 years (range 16–93) and 406
patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of
the patients showed at least one deleterious variant in all 25 investigated
genes and 26.4% in the defined 16 risk genes. Deleterious variants were most
prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2 (1.1%)
genes. The prevalence of deleterious variants did not differ significantly
between patients at primary diagnosis and relapse. The prevalence of
deleterious variants in BRCA1/2 (and in all 16 risk genes) in patients <60
years was 30.2% (33.2%) versus 10.6% (18.9%) in patients ≥60 years. Family
history was positive in 43% of all patients. Patients with a positive family
history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4%
(17.6%) and histologic subtype of high grade serous ovarian cancer versus
other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2%
(14.8%), respectively. Testing only for BRCA1/2 would miss in our series more
than 5% of the patients with a deleterious variant in established risk genes.
Conclusions 26.4% of all patients harbor at least one deleterious variant in
established risk genes. The threshold of 10% mutation rate which is accepted
for reimbursement by health care providers in Germany was observed in all
subgroups analyzed and neither age at primary diagnosis nor histo-type or
family history sufficiently enough could identify a subgroup not eligible for
genetic counselling and testing. Genetic testing should therefore be offered
to every patient with invasive epithelial ovarian cancer and limiting testing
to BRCA1/2 seems to be not sufficient
