Advances in genetic counseling,
testing and other services

Breast cancer affects one in eight women over their lifetime. Women with additional family members also affected with breast cancer raise special concerns regarding the possibility of hereditary breast cancer. Individuals in these high-risk families may have up to a 65 percent risk of developing breast cancer by age 70 years. Deleterious changes in several different genes, including BRCA1 and BRCA2, are found in a significant portion of individuals with early-onset cancer or a strong family history of cancer.

Evaluating individuals most appropriate for genetic testing is aided by careful analysis of the family history. For example, if a patient has had breast cancer before she is 50 years old, and she also has a first- or second-degree relative who also had breast cancer at a young age, we would estimate that her risk of carrying a genetic alteration in either the BRCA1/2 genes to be approximately 30 percent. Medical and family histories that include both breast and ovarian cancer may indicate an even higher risk for carrying a mutation in the BRCA1/2 genes, maybe as high as 79 percent. However, less than 7 percent of women with breast cancer over age 50 are carriers of a BRCA1/2 mutation, even with another single family member with breast or ovarian cancer.

All cancer originates from genetic changes, i.e., changes in the DNA molecules that make up genes. However, individuals with hereditary cancer syndromes have increased cancer risks due to genetic changes that were inherited from either parent. Six different genes have been extensively characterized, in which mutations within these genes confer substantial risk for breast cancer. The most studied of these genes are BRCA1 and BRCA2, which were first identified in 1994. Clinical testing for changes in these two large genes has been available since 1996 using DNA sequencing technology. In 2006, the testing laboratory Myriad Genetics began offering an additional test to identify large deletions or rearrangements of the BRCA genes. Myriad recently released data from more than five years of rearrangement testing, called BART testing. Surprisingly, this data reports significant variability of the incidence of rearrangements among different ancestries. For example, among BRCA families with Latin American and Caribbean ancestry, 20.5 percent of mutations were found to be large rearrangements, as compared to 9.7 percent from families with European ancestry. This study demonstrates the expanding list of contributing factors that should be considered when ordering BRCA testing, as BART testing is not automatically included in the standard genetic testing panel for these two genes.

Research continues to identify additional genes and genetic regions that can confer small additional risks for breast cancer, separate from BRCA1/2. Single length polymorphisms or SNPs are an emerging area of cancer genetics investigations. Many distinct regions have been identified and they can either increase or decrease cancer risk by 1 to 3 percent. However, the clinical significance and utility of these genetic regions have not yet materialized. The risk assessments based on these newest genetic tests are drawn from population studies and are difficult to apply to a given woman's specific cancer risks.

Pharmacogenetic testing to improve breast cancer treatment is continuing to emerge. Genes that influence the metabolism and efficacy of tamoxifen have been characterized and genetic testing is available. Until more confirmatory research has been done, many clinicians are hesitant to change widely accepted practice patterns around tamoxifen based on a single genetic test for CYP2D6 genotype. The outcome of such changes in therapy has not been validated in prospective clinical trials.

Genetic counseling for cancer family histories is limited by access to the service. In the state of Indiana, there are fewer than 60 licensed genetic counselors and medical geneticists. In order to improve access, Community Health Network and The Center for Genetic Counseling are developing a telemedicine program. Patients can receive genetic counseling via remote computer access. Alternate service delivery models of genetic counseling using telephone counseling are available commercially. However, most cancer genetic counseling requires visual aids which enhance the patient and their families' understanding of the genetics of cancer and its heritability. Without visual aids and a pedigree, the counselor may be hampered in effectively communicating the risk for cancer in the family. The Community Health Network web-based system will use web-based videoconferencing technology to blend the effectiveness of face-to-face counseling with the convenience of telephone counseling. We believe that this innovative service will greatly improve access to cancer genetic counseling services.

Patients within hereditary cancer syndrome families present unique challenges and opportunities for the health care team. Community Health Network and The Center for Genetic Counseling continue to bring the latest knowledge, testing strategies and innovative use of technology to optimize our patient's outcomes and health.

—Glenn J. Bingle, M.D., Ph.D., FACP, and Renee Jones, M.S., CGC