Questionnaire helps identify women who have inherited genetic mutations that increase their risk for breast or ovarian cancer

A simplified way for patients to report and update their family medical histories could help identify women who have inherited genetic mutations that increase their risk for breast or ovarian cancer.

In the November issue of the journal Cancer, researchers from the Massachusetts General Hospital (MGH) Cancer Center report how a questionnaire completed by women coming to the center for mammograms can detect those at increased risk, which could signal the need for further screening and preventive therapies and allow earlier diagnosis. The study is receiving early online release.

"In order to identify patients at high risk, physicians must take thorough family histories and then accurately interpret that information, something that can be difficult since many nuances can determine risk," says Kevin Hughes, MD, of the MGH Surgical Oncology Division, the study's senior author. "In addition, family history can change over time if a patient's relatives develop cancer. We need an easier way to both update data and reevaluate each patient's situation."

Previous research has shown that about 20 percent of women who develop breast or ovarian cancer have family histories that suggest they may have inherited a mutation that would put them at elevated risk. In comparison, the family histories of only 3 to 6 percent of women who had not developed those cancers indicate elevated risk. The current study was designed to further investigate the extent to which women with these mutations are not being identified and to evaluate a less labor-intensive method of collecting and analyzing family history information.

During the eight-month study period, about 14,000 women who came to the Avon Breast Evaluation Center at MGH completed a questionnaire on their family history of breast or ovarian cancer, whether they had developed any tumors and related factors. The information was gathered either with written questionnaires scanned into a computer or on handheld tablet computers. It was downloaded into a database that was immediately available to the patients' physicians and was later analyzed with a protocol designed to evaluate the risk that the patients carried mutations in BRCA1 or BRCA2, the so-called "breast-cancer genes."

Among the 1,764 participants who had been diagnosed with breast or ovarian cancer, 20.6 percent had family histories indicating elevated risk of one of the tumor-associated mutations. Risk levels were even higher among participants who'd had ovarian cancer and those of Ashkenazi Jewish ancestry, a group known to have higher incidence of the mutations. The earlier study that found similar risk levels used a more complicated risk-assessment procedure conducted by a genetic counselor, a resource not available in many centers.

"We wanted to show we could identify these high-risk women with an automated system that provides accurate information without requiring more work for our staff, an approach that has been tried in very few centers worldwide," says Hughes. "In addition to verifying the utility of this strategy, these results remind us how many women who should be tested for these genetic mutations are not being screened." Hughes is an assistant professor of Surgery at Harvard Medical School.

The researchers note that women diagnosed with the cancer-associated mutations can pursue a number of options. Preventive approaches include treatment with tamoxifen or contraceptive drugs and prophylactic removal of the breasts or ovaries. More frequent screenings with mammograms and MRI imaging can lead to early diagnosis. And for those who develop tumors, mutation status can help determine the best treatment strategies. The team is continuing to administer the questionnaire to patients at the MGH and will begin doing so at Newton-Wellesley Hospital, an affiliated institution, in the near future. They also will investigate methods for informing women of their mutation status and managing the expected increase in patients requiring follow-up care.