Consider Genetic Testing for Hereditary Cancers


WASHINGTON — Clinical genetic testing for the BRCA1 and BRCA2 genes allows physicians to more precisely identify who is at high risk for certain cancers, Dr. Karen H. Lu said at the annual meeting of the American College of Obstetricians and Gynecologists.

Armed with this knowledge, physicians can recommend risk-reducing strategies including prophylactic surgery, said Dr. Lu, associate professor of gynecologic oncology and co-clinical medical director of the Clinical Cancer Genetics program at the MD Anderson Cancer Center in Houston.

For example, performing a bilateral salpingo-oophorectomy in someone who is a BRCA mutation carrier decreases their risk for ovarian cancer by 85%–95%, she said.

“In someone who is at such high risk for developing a disease for which we have no current effective screening, performing this surgery effectively saves their lives,” Dr. Lu said.

In terms of breast cancer management, a 35-year-old woman with breast cancer and a strong family history might otherwise be advised to undergo a lumpectomy, radiation, and chemotherapy.

However, if she knew she carried either a BRCA1 or BRCA2 mutation, she might choose to undergo a bilateral mastectomy with reconstruction upfront to decrease her risk of developing a second cancer, Dr. Lu said.

Physicians can identify women who may be good candidates for genetic testing by asking a few targeted questions during the annual visit, Dr. Lu said.

The hallmarks of hereditary cancers are generally a younger age of onset, more than one cancer in a single family member, and multiple individuals in a family who have developed cancer, she said.

Consider asking these three questions:

▸ Do you have multiple members of your family who have had breast, ovarian, colon, or uterine cancer?

▸ Is there anyone in your family who has had both breast and ovarian cancer?

▸ Is there anyone in your family who has had these cancers under the age of 50?

Keep in mind that these cancers can be inherited through both maternal and paternal relatives, so ask about cancer on the father's side as well, Dr. Lu said.

Also consider ethnicity, she said. The prevalence of BRCA genes in the general population is about 1 per 500, or 0.2%.

However, some populations have “founder” mutations in the BRCA1 and BRCA2 genes that increase their risk. For example, the Ashkenazi Jewish population has three founder mutations that put them at about a 10-fold increased risk for having a BRCA1 or BRCA2 gene mutation. So instead of a 0.2% risk of having the mutation, there is a 2%–3% frequency of the mutation among this population.

Overall, about 5%–10% of all cancers are hereditary. For breast cancer, that translates into about 10,000 to 20,000 cases a year in the United States and about 2,000 cases each year of ovarian cancer.

The frequency of BRCA1 or BRCA2 carriers in the United States is about 1 in 500 in the general U.S. population. “Individuals who carry these mutations have staggering risks of cancer,” Dr. Lu said.

The BRCA1 mutation carries a lifetime risk of 50% to 85% for breast cancer and a 40% to 60% risk of developing a second breast cancer. And there is a 20%–50% lifetime risk for ovarian cancer with the BRCA1 gene. This is significantly higher than the lifetime risk in the general population of about 11% for breast cancer and 1.7% for ovarian cancer.

In addition, the BRCA2 gene carries a lifetime risk of 50%–85% for breast cancer and a 10%–25% risk for ovarian cancer.

Genetic testing can be useful both for cancer patients who want to find out if they face an increased risk of a second cancer and for women unaffected by cancer but with a strong family history.

The ideal person to test in a family is someone who has had ovarian or breast cancer, Dr. Lu said. In the case of a patient unaffected by cancer with a strong family history, advise them to be tested with someone in their family who has had cancer. The person who has had cancer must be tested first.

Pretest counseling is critical, Dr. Lu commented. Patients need to be aware of the range of possible results and the limitations of the test. They may also have questions about genetic discrimination, she said.

The test itself is a simple blood test and does not require fasting. It generally costs about $3,000 to do a full analysis with complete sequencing of both the BRCA1 and BRCA2 genes. The cost of predictive tests on a previously identified familial mutation is about $200–$400.


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