A Historical Overview of the Evolving Landscape of Genetic Counseling

Genetic counseling as a profession began in 1969 with the establishment of the first master’s level graduate program in genetic counseling; as a process, however, it has evolved over a longer period of time. The term “genetic counseling” was coined in 1947 by Sheldon Reed, a geneticist, who used the term to describe the process of providing genetic information and support to families. He believed that an “important requirement of the counselor was to have a deep respect for the sensitivities, attitudes and reactions of the patients.”¹ Physicians who worked in early medical genetics clinics hoped to gain an understanding of the genetics involved in disease. At that time, however, laboratory tests for genetic conditions did not exist and the practice of genetic counseling was limited.

During the 1950s and 1960s, cytogenetics advanced and amniocentesis emerged, making it possible for physicians to diagnose chromosomal abnormalities in their patients. Additionally, amniocentesis could be used to detect Barr bodies in fetal cells, allowing the prediction of fetal sex.² This information could then be applied to families at risk for a sex-linked genetic disorder. Eventually, by the mid-1960s, amniocentesis was used to construct a human karyotype of the fetus.³ Amniocentesis did not come without risks, however; not only did the information from amniocentesis have to be conveyed to the family but the risks, limitations, and benefits of the procedure had to be explained to them as well. Medical professionals realized that conveying genetic information required a particular subset of skills, and the first genetic counseling programs came into being. With the expanded use of genetics in medicine, genetic counseling was no longer limited to a few specialty centers, and the number of centers offering genetic counseling services grew from 10 in 1951 to 287 in 1977.4

As science progressed into the 1980s, advances were seen in cytogenetics, molecular genetics, and biochemical genetics. The role of the genetic counselor in the prenatal setting expanded to include providing information obtained from examining enzymes in amniotic fluid.⁵ Additionally, genetic counselors entered predisposition testing when the gene for Huntington’s disease was mapped with DNA markers.⁶ Predisposition testing continued to grow in the 1990s as several cancer-predisposing genes were cloned. Mutations in these genes were shown to cause an increased risk for cancers, such as colon, breast, and ovarian.⁷ As centers began offering predictive DNA testing to affected individuals and family members at risk, genetic counselors entered a new sector: cancer counseling.

The sequencing of the human genome and identification of cancer predisposition genes, such as BRCA1 and BRCA2, rapidly increased the need for individuals with cancer genetic expertise and experience in genetic counseling. Additionally, direct-to-consumer marketing of hereditary cancer genetic testing and celebrities announcing their own BRCA status have furthered society’s awareness of genetic testing. In turn, healthcare professionals have faced increased pressure to incorporate genetic testing into their practice—either by providing in-house genetic counseling or referring to experts for consultation. Over the last decade, genetic testing has increasingly been performed through community practitioners without the involvement of a trained genetics professional.⁸ In addition to increased awareness, the landscape of cancer genetic testing has also been impacted by technological advances and policy decisions.

Since the discovery of BRCA1/2, there have been tremendous advances in DNA sequencing technologies. In 2003, the Human Genome Project completed its version of the human genome sequence, which took approximately 15 years of research and cost $2.7 billion.^9,10 However, over the last few years, the cost of generating sequencing data has dropped to less than $10,000 and takes a matter of a few weeks.¹¹ It is anticipated that costs will drop below $1000 and take just days (potentially hours) to complete, recognizing, of course, that this does not factor in the time and cost needed for interpretation and return of the results to the patient. Such changes have resulted in expanded testing options for inherited cancer, with the paradigm for genetic testing expected to change as well.

Since 2012, multigene tests have been available on a clinical basis. These tests allow for multiple genes to be analyzed for mutations simultaneously, at a cost that is often comparable to testing for a single inherited condition. No longer does a clinician have to rely on a genetic testing strategy focused on eliminating differential diagnoses, but he or she can begin with a multigene test incorporating many genes linked to a particular cancer site. However, at the same time, the clinician will also be faced with a higher likelihood of receiving a variant of unknown significance, an incidental finding, and/or a gene mutation for which medical guidelines have not yet been determined.

As a result of technological changes, cancer genetic counseling continues to evolve. Multigene tests allow a clinician to cast a wider net and analyze several to hundreds of genes. Clinicians can even opt to select for genes outside of the inherited cancer arena. The traditional model for delivering cancer genetic counseling services begins with an in-person pretest genetic counseling session followed by a results disclosure session, both conducted by a certified or credentialed genetics professional trained to provide a detailed risk assessment that includes a differential diagnosis, education, and medical management options for hereditary cancer.¹² Such an approach is often not feasible when genetic testing involves a multigene test, and the optimal approach is currently unknown.¹³ Counseling strategies appear to be shifting toward one that relies on a broad pretest session that covers topics essential for informed consent, such as conditions being tested for and possible genetic test results, but that defers detailed discussion of specific conditions to the posttest session, during the disclosure of genetic test results.¹⁴

The ruling in June 2013 by the Supreme Court of the United States, which concluded that genes could not be patented,¹⁵ further changed the marketplace for genetic testing. At the time, approximately 20% of human genes were patented,¹⁶ including BRCA1 and BRCA2. Upon the Supreme Court’s decision, several laboratories immediately added BRCA1/2 to their testing menu and included it on their multigene panels. As a result, clinicians were able to use a single panel to search for mutations in multiple genes linked to inherited breast and/or ovarian cancer rather than relying on multiple laboratories and tests for comprehensive analysis.

It is interesting to note that multigene panels are providing more insight into the phenotypes of hereditary cancer syndromes. Indeed, several studies have found patients with germline mutations that do not meet classic testing criteria and which would likely have been missed if testing relied on a single-gene testing approach.^17-20

With the significant decreases in the cost of genotyping, it is not unreasonable to postulate that individuals may one day undergo full exome or genome analysis not only to determine which medical conditions they are at risk for, but also for pharmacogenomic applications. It is important to remember that genetics is different from other topics in medicine as it underlies all of pathophysiology and will likely increasingly influence healthcare as technology continues to evolve. The shift to multigene testing options is the first step in that direction. With these technological advances enabling more individuals to be identified as being at risk, however, the complexities of delivering genetic services and managing genetic risk will also be magnified. As such, genetic counseling for inherited disease, such as cancer, must continue to evolve.

References
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