Better physician education and consultation with genetics professionals when recommending genetic testing for healthy relatives of cancer patients could lower costs and increase the value of the testing, said a cancer geneticist from the NCI-designated Dan L Duncan Cancer Center at Baylor College of Medicine, who surveyed physicians to determine their level of knowledge.

"In the last several years, we have noticed an increase in referrals from physicians ordering comprehensive genetic tests and seeking help for interpretation of results,"said Dr. Sharon E. Plon, director of the Baylor Cancer Genetics Clinic at BCM.

"This made us curious as to how non-genetic physicians interpret familial genetic cancer history and ultimately make decisions about genetic testing."

"What we observed in this study is that physicians are choosing more comprehensive testing for healthy relatives than current guidelines recommend, regardless of their experience or specialty,"said Plon.

The results of her study, which dealt with testing for genes that increase risk for breast and ovarian cancer, appear in the current online issue of Genetics in Medicine. The results will also appear in the February print edition of the journal.

She and her colleagues sought to discover how often doctors would order tests compared to recommendations from the National Comprehensive Cancer Network.

Testing for healthy women

In a survey of 225 Texas physicians, Plon and her team asked doctors about whether and what kind of genetic testing they would order for healthy women between the ages of 41 and 43 who had a relative with breast or ovarian cancer who had had gene testing done already.

In two of the presented cases, the patient with cancer had a known deleterious mutation in the BRCA1 gene that was associated with increased cancer risk. In two, the patient had a gene variant where there was uncertainty about the impact on breast or ovarian cancer risk.

A comprehensive gene test looking for mutations in the BRCA1 and BRCA2 genes that raise the risk of breast and ovarian cancer is recommended for women with the cancers. However, the National Comprehensive Cancer Network recommends that healthy first-degree relatives (siblings and daughters) of women found to have a deleterious BRCA1 or BRCA2 mutation receive a simpler gene test that looks only for the mutation identified in their families. It recommends no gene testing when a patient has a variant with uncertain significance.

Unnecessary genetic testing cost

In the survey, when the physicians considered a case in which a deleterious BRCA1 mutation was identified in a mother with cancer, 98 percent recommended a genetic test, but only 20.4 percent chose the simpler option that looks for the specific mutation found in the mother. In two cases where the gene variant with no known increased cancer risk was found, approximately 82 percent of physicians recommended genetic testing. The comprehensive genetic testing was more commonly recommended in all cases than the simpler option. Only 2 percent of physicians chose the network's recommended testing in all cases.

"In both situations, the comprehensive test was selected most with an almost nine-fold increase in unnecessary genetic testing cost across all cases,"said Plon. The comprehensive genetic test costs $3,340 on average as opposed to $475 for the simpler option. In two cases, no gene testing at all is recommended.

"It's not clear whether physicians understand these differences and follow National Comprehensive Cancer Network guidelines on which type of test, if any, is necessary and appropriate for the cancer patient's relatives,"said Plon.

Survey to assess current recommendation

Plon collaborated with the Texas Medical Association and randomly surveyed physicians in active clinical practice from five different specialties across Texas including family medicine, internal medicine, obstetrics and gynecology, general surgery and hematology and oncology.

In the second part of the survey, physicians answered questions about their own experience and education with genetic testing.

"We found no statistical difference when physicians had experience ordering BRCA 1/2 tests in their own practice versus those who had no experience,"said Plon.

Involvement of genetic counselors

"There was clear misunderstanding about the differences in single site testing and comprehensive testing,"said Plon. "This is an important area where using genetic professionals would be beneficial."

"Utilization of genetic professionals is a requirement in other countries,"said Plon. "It's not in the United States and one reason has been the potential increase in cost by involving genetics professionals. We find involving them may actually save on overall costs, by decreasing the ordering of more expensive test or no test if necessary."

Risk management recommendations

On the other hand, physicians appropriately suggested more intense screening for healthy women with the deleterious BRCA1 mutation than for those with the variant of uncertain significance – although they suggested more intense surveillance in both groups than for women who had not had gene testing.

They were more likely to suggest ovary removal (63 percent) in women with the deleterious BRCA1 mutation than in women with the variation of uncertain significance (13 percent). They suggested regular breast MRI in women with the deleterious BRCA1 mutation more often (76 percent) than in women with the variation (38 percent). However, the suggestions for relatives with a variant were still more intense than a similar woman with no testing.

"This is actually quite positive,"said Plon. "Overall, the majority of physicians understood that women with the deleterious mutation need more risk management, but education is still needed to improve the management of women with variants."

Plon is also a professor of pediatrics – hematology/oncology and molecular and human genetics and the Human Genome Sequencing Center at BCM, director of the BCM M.D./Ph.D. Medical Scientist Training Program, director of the Neurofibromatosis Clinic at BCM and Texas Children's Hospital and a member of the Texas Children's Cancer Center.

Others from BCM involved in this research include Paul Cooper, Bethany Parks, Dr. Shweta Dhar, Dr. P. Adam Kelly, Dr. Armin Weinberg, Tao Wang and Dr. Susan Hilsenbeck. Stephanie Staggs from the Texas Medical Association was also involved.

This projected was funded by a grant from the National Human Genome Research Institute.