Women with ovarian cancer who have a family history of breast or ovarian cancer, and are younger than 45 if breast cancer in a near relative makes up that history, are more likely to have inherited BRCA mutations and could benefit from a genetic test to see if they are carriers, a study reports.
Using data covering more than 2,000 patients, researchers built a decision tree to identify those at greater risk of carrying the mutations. They propose the tool could serve as a reasonable and cost-effective way of selecting patients for BRCA testing rather than a widespread screening of all — an issue of considerable debate.
The study, “BRCA germline mutation test for all woman with ovarian cancer?,” was published in the journal BMC Cancer.
Specific inherited mutations in the genes BRCA1 and BRCA2 increase a person’s risk of breast and ovarian cancers, and are also associated with increased risks of several other cancers.
A person’s likelihood of ovarian-fallopian cancer ranges from 39% to 63% for carriers of BRCA1, and 16% to 27% for those with BRCA2 mutations. Both are considerably higher than the 1% to 2% mean risk in the overall population.
Knowing a patient’s BRCA status can provide useful information in estimating prognosis and guiding treatment decisions. But no general agreement exists as to which patients are most likely to be carriers and should receive a BRCA test.
Identifying such patients is not straightforward. According to several studies, an important fraction (about 40%) of BRCA-mutated ovarian cancer patients may not have a family history. Age of onset, family history of breast and/or ovarian cancer, and tumor histology seem to be the three most important factors for referring women for a BRCA test.
But some argue that women not meeting these criteria can still have a substantial probability of carrying a BRCA mutation. This has prompted several researchers, professional societies, and patients organizations to propose widespread BRCA testing of all ovarian cancer patients.
Cost-benefit of such an approach, compared to standard practice, is yet to be demonstrated.
In an effort to provide new insights and develop testing criteria, researchers analyzed a database comprising clinical and molecular information — including germline (inherited) BRCA analysis — of 2,222 women diagnosed with ovarian cancer in the U.K. and the U.S.
Overall, 178 (8.1%) of the patients had a disease-associated BRCA mutation, 84 in BRCA1 gene and 94 in BRCA2.
Additional analysis showed that BRCA mutations were more common in women who had epithelial tumors (10.7% patients), less differentiated tumors (11.0%), and who were younger (13.4%).
Based on this data, researchers build a decision tree to identify women with a greater or lesser likelihood of being BRCA mutation carriers.
They found that probability was high (40% of BRCA mutation carriers) in patients younger than 46 with a family history of breast cancer in a first-degree relative. Patients with a family history of ovarian cancer, irrespective of age, were the second group at highest risk (29% of carriers).
In contrast, that probability was very limited (lower than 1% of carriers) in people without a family history of ovarian or breast cancer, earlier stage disease (stage I-II), and with tumors with a differentiation grade I-II.
Taken together, researchers identified a larger group (66%) of patients who were less likely to carry a mutation (3.5% of carriers), and another group of women (24%) who were at higher risk — with a probability greater than 17% — of carrying a malignant mutation.
“The possibility to better select candidates to the test is a feasible approach and, from this perspective, our regression tree analysis could represent a reasonable practical approach,” the researchers wrote.
They are now comparing their approach with a genetic risk prediction model (BRCAPRO) to see which provides a more reliable way of selecting candidates for a BRCA test.
“While some countries are already considering national wide roadmaps to facilitate and improve BRCA genetic testing rates, we suggest that there is no evidence that delivering a widespread BRCA testing for OC [ovarian cancer] patients is cost effective with respect to standard practice for preventive and therapeutic purposes,” the researchers said.
“A better selection of patients to be tested together with new predictive biomarkers … are urgently needed,” they concluded.