- Ask every patient: ”Has anyone in your family had breast cancer under the age of 35, or colorectal, uterine, or ovarian cancer?
- Genetic testing is appropriate only when pre- and post-test counseling is available, the test can be interpreted, and the results will help in medical and surgical management.
- Oral contraceptives may reduce risk by 10% per year for up to 5 to 7 years of use.
- Bilateral salpingo-oophorectomy in BRCA carriers reduces the risk of ovarian cancer by more than 90% and the risk of breast cancer by more than 50%.
A 42-year-old woman of Ashkenazi Jewish ancestry, whose mother had a diagnosis of ovarian cancer a year earlier, is worried that she may also be at risk.
Her family has experienced no other cases of breast, colorectal, or ovarian cancer. She has 2 children and has used oral contraceptives for 9 years.
Primary prevention is an alternative to diagnosis of ovarian cancer at an early stage—a goal that is all too often unattainable.
If we identify women with increased risk based on their family history, environmental exposure, hormone use, or reproductive experiences, we can counsel them about lifestyle changes, chemoprophylaxis, or preventive surgery, depending on their reproductive desires and overall ovarian cancer risk.
Using 2 hypothetical cases, this article describes a quick history to screen for potential high risk, and summarizes what we can advise concerned patients, based on findings to date.
- genetic risk assessment
- when to refer to a genetic counselor
- risk factors
- oral contraceptives for primary prevention
- prophylactic surgery
Despite advances in medical and surgical therapies, ovarian cancer remains the deadliest gynecologic malignancy and the fifth leading cause of cancer deaths among women in the United States. This year the disease will strike an estimated 25,400 women in this country and kill more than 14,000.1
Early detection versus primary prevention
One of the biggest problems is well known: In its early stages, ovarian cancer often is asymptomatic. Even when advanced, symptoms tend to be vague and are often dismissed by patients and their doctors. By the time the diagnosis is suspected, most women have disease beyond the ovary.
Because curability greatly depends on stage at presentation, much research is directed toward early detection. Advances in high-resolution imaging and novel blood or urine tumor markers may one day offer effective screening, but at present these methods are unproven.
3 genetic syndromes
Three genetic syndromes account for the vast majority of familial ovarian cancer and approximately 10% of all ovarian cancers. They are:
- breast-ovarian cancer syndrome,
- site-specific ovarian cancer syndrome, and
- hereditary nonpolyposis colorectal cancer syndrome (HNPCC) (Lynch II).2
HNPCC is caused by mutations in a series of genes responsible for repairing errors in DNA replication. Inactivation of these so-called mismatch repair genes results in a high incidence of right-sided colon cancer, endometrial cancer, and ovarian cancer.3
Gene mutations in different populations
The lifetime risk of developing ovarian cancer in the United States is about 1.4%. However, among women with BRCA1 or BRCA2 mutations, the risk rises to 20% to 60%.4
These genes also impart a significant lifetime risk of breast cancer in women and, in the case of BRCA2, in men as well.
Less than 0.15% of the general population carries BRCA1 or BRCA2 mutations. However, the carrier rate is dependent on ethnic background.5 Founder mutations have been identified among multiple unrelated families in Iceland, the Netherlands, and Sweden, and among Jews of Central or Eastern European descent (Ashkenazi).
The best described founder mutations are the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2, occurring in Ashkenazi Jews at a carrier rate of 2%.6
Ovarian cancer in Ashkenazi women more likely genetic than sporadic
Although an Ashkenazi woman is no more likely to develop ovarian cancer than a noncarrier, if she does develop the disease, it is far more likely to be genetic rather than sporadic.
Consequently, if a woman of Ashkenazi Jewish descent develops ovarian cancer, there is a 40% chance she carries a mutation in one of these 2 genes.7 Her first-degree relatives (mother, sisters, daughters) have a 20% risk of being gene carriers (50% in autosomal dominant transmission).
Therefore, an Ashkenazi Jewish woman needs only 1 first-degree relative with ovarian cancer to be considered for further genetic counseling.