Genetic Counseling Clinic at AIIMS (New Delhi)

Abstract

The field of genetic counseling in India has enormously transformed over the past few years. Genetic counseling is a communication process which deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. Genetic counseling is not merely having a conversation based on genomic data. It addresses the “information needs” of a particular patient, and customizes a session according to each patient’s individual circumstances, thereby aiding in decision-making. In 2012, AIIMS (New Delhi) became the first tertiary care center in North India to provide genetic counseling for cancer. Among 200 cases that were referred for genetic counseling to the AIIMS clinic at the Department of Surgical Disciplines, about 30% of patients chose to undergo testing. Five cases of BRCA1/2 mutation were found conforming to the hereditary breast and ovarian cancer syndrome. There was one case of TP53 mutation conforming to Li-Fraumeni syndrome. One case each of Xeroderma Pigmentosum (XP) and Cowden’s syndrome was also detected. All these cases were offered risk-reducing measures and put under life-long surveillance as per protocol. Their family members were also offered genetic counseling and subsequent testing if they agreed. Cancer genetic counseling service was a new exercise, and hence, several challenges were faced. The clinical utility of genetic testing, coupled with counseling, should be established by trials. Documenting the achievements of counseling by surrogate parameters like “improved recruitment rate of patients for genetic tests” and “improved patient satisfaction levels” will go a long way in garnering the much needed institutional support.

The field of genetic counseling in India has enormously transformed over the past few years. From a handful of genetic counselors a decade ago, currently, the field has blossomed with almost about 100 trained and certified counselors spread across the country. This growth was triggered and aided by a growing awareness among clinicians about genetic counseling and testing, more affordable tests, widespread availability, and a wider range of options of risk reduction being offered.

Now, what is genetic counseling?

The art of genetic counseling involves combining the knowledge of genetics, traits of compassion, and empathy along with skills of listening and communicating.

The formal definition of counseling as cited and published in the American Journal of Human Genetics, in 1974, by FC Fraser is:

“Genetic counseling is a communication process which deals with the human problems associated with the occurrence, or risk of occurrence of a genetic disorder in a family. This process involves an attempt by one or more appropriately trained person(s) to help the individual or the family to comprehend the medical facts, including the diagnosis, the probable course of the disorder and available management, to appreciate the way heredity contributes to the disorder and the risk of recurrence in specified relatives, to understand the options for dealing with the risk of recurrence, to choose the course of action which seems appropriate to them in view of their risk and their family goals and act in accordance with that decision, and to make the best possible adjustment to the disorder in an affected family member and to the risk of recurrence of that disorder.”

Though it may seem to some that genetic counseling is merely having a conversation based on genomic data, it actually involves much more than that. It addresses the “information needs” of a particular patient, and customizes the session according to each patient’s individual circumstances, thereby aiding in decision-making.

An ideal genetic session is composed of the following aspects:

• Assessing an individual’s risk of a genetic disorder

• Preparing the individual for genetic testing

• Communication of results

• Assisting in management of disease

• Reaching out to the extended family members

Genetic Counseling Clinic at AIIMS Surgical Unit

In 2012, Department of Surgical Disciplines, AIIMS (New Delhi) became the first tertiary care center in North India to provide genetic counseling for cancer. Since 2013, after the famous Hollywood actress Mrs. Angelina Jolie underwent bilateral risk-reducing mastectomy and bilateral prophylactic salpingo-oophorectomy after being detected with BRCA gene mutation; the awareness about genetic tests was on the rise by virtue of this so called “Angelina Jolie effect”. That, coupled with affordable tests gradually becoming available in India, led to an appreciable increase in both the demand and feasibility of genetic counseling. This led to a greater need felt for more trained counselors.

In oncological settings, genetic counseling was offered to all cases with:

• Sporadic early onset breast cancer (< 45 years) or a triple negative breast cancer (< 60 years)

• Male breast cancer at any age

• Early onset colon, ovarian, uterine, pancreatic, diffuse gastric, or renal cancer (< 50 years)

• Medullary thyroid cancer or adrenocortical carcinoma at any age

• Multiple primary cancers in one individual (e.g., bilateral breast cancer, breast/ovarian, colon/uterine, uterine/renal/thyroid, or multiple primary melanomas)

• Individual with multiple and/or early onset gastrointestinal polyps (multiple polyps, > 15 GI polyps, or > 5 hamartomatous or juvenile polyps)

• Hereditary cancer syndrome identified

• Hereditary family-specific mutation identified

• Family history of any cancer

Each genetic counseling session involved two sections—(1) pre-test counseling session and (2) post-test counseling session.

Pre-test genetic counseling was offered to all patients referred to the clinic. The following aspects were discussed in depth:

1. What are genes and how a change/mutation in them results in cancer:

Genes and DNA sequence as a basic unit of heredity and protein coding, presence of genes as part of the chromosomes inside the cell nuclei, and meaning and role of oncogenes and tumor suppressor genes would all be discussed along with the meaning of genetic mutations and the role of mutations in cancer.

• 2.What are hereditary cancers:

Discussions would include gene mutations in sporadic cancers, inherited mutations through germline cells, and increased risk in cases with inherited mutations.

• 3.Autosomal type of inheritance:

Diploid cells and pattern of inheritance, autosomal dominant traits, inherited mutations, and two-hit hypothesis would be explained to the patients.

• 4.Recommendation of specific tests and/or testing protocol involving series of tests based on the outcome of each test in the series
• 5.
  Results which we might get after genetic testing:

  1. Positive—A change is identified and is known to cause the syndrome
  2. Negative—No change identified
  3. Variant of unknown significance—A change is identified; however, its oncogenic potential or role in disease causation, if at all, is unknown.
• 6.Pros and cons of genetic testing:

1. Pros

   • I.
     A sense of relief from uncertainty
   • II.
     In-depth knowledge about one’s cancer risk
   • III.
     Awareness to help make informed medical and lifestyle decisions
   • IV.
     Opportunity to help educate other family members about potential risk
2. Cons

   • I.
     Testing may increase anxiety and stress for some individuals
   • II.
     Testing does not evaluate a person’s risk for sporadic cancers
   • III.
     Results in some cases may turn out to be inconclusive or uncertain

• 7.Predictive testing for at risk relatives:

If the affected person was tested and found positive, the unaffected family members were offered predictive testing.During the post-test session, the outcomes of the report would be discussed. If a mutation was found, management decisions would be made or modified by taking into consideration both the patient’s disease status and the mutation detected. For healthy individuals detected to have genetic mutations, surveillance and options of prophylactic surgery would be discussed. An understanding of the risk for other first-degree relatives would be inculcated, and plans to convey this information to the concerned relatives would be drawn up. A pre-test genetic counseling would be offered to every related individual who would come for their genetic test.

The surveillance protocol and prophylactic surgical measures in individual cases would be adopted from the prevalent NCCN guidelines [1, 2]. The post-test counseling sessions would be done in the presence of the referring clinician as it would involve a detailed discussion about the management of the disease. The disease management would be greatly dependent on the age, disease status, specific mutation, and personal choice of the patient [3].

The key pillars behind the success of the counseling program are[4, 5]:

• Rapport building at the beginning of the session to make the counselee comfortable to open up

• Non-directive counseling in order to help the patient and their families to arrive at a conscious decision based on their own understanding, constraints, and circumstances

• Appreciation, empathy towards, and support for the counselee’s situation and choices

• Summarizing the session along with issuance of a genetic counseling summary letter

Outcomes

Among 200 cases that were referred for genetic counseling to the AIIMS clinic at the Department of Surgical Disciplines, about 30% patients chose to undergo testing. Their samples were sent for hereditary cancer panel on NGS (next generation sequencing). Five cases of BRCA1/2 mutation were found conforming to the hereditary breast and ovarian cancer syndrome. There was one case of TP53 mutation conforming to Li-Fraumeni syndrome. One case of Xeroderma Pigmentosum (XP) was picked up. One case of Cowden syndrome was also detected. All these cases were offered risk-reducing measures and put under life-long surveillance as per protocol [6]. Their family members were also offered genetic counseling and subsequent testing if they agreed.

Challenges and Constraints

The cancer genetic counseling service in the department was a new exercise, and hence, several challenges and constraints had to be put up with, such as:

• Awareness and uptake from clinicians: Being a new and once a week exercise, the service received a lukewarm response, and there were just sporadic referrals from some of the clinicians to begin with. However, over time, it gained momentum and many clinicians became aware of the service and its benefits. Slowly the referral rates went up.

• Infrastructure: An ideal counseling session setting involves a private room without any disturbance. Enough space and adequate chairs are required for a larger family group along with the clinician, counselor, and any assistant. Display charts and computer-based presentations make communication easier. Such ideal setting was not always available in the weekly clinic.

• Testing uptake: The tests offered were often found to be expensive by many of the patients who declined to undergo such tests. Hence, the recruitment rate was poor.

• Post-test counseling/testing follow-ups: Many patients were from other cities and did not come back for post-test counseling or the next test in the series as per protocol.

• Lack of testing facility within AIIMS: The samples had to be sent to a laboratory situated outside AIIMS. This required meticulous coordination. Some of the patients were apprehensive about the choice of laboratories, its credentials, and so on.

Lessons Learnt for the Future

The genetic counseling clinic was eventually appreciated by most of the referring clinicians, patients, and their families. Looking back, the clinic could have achieved greater impact if there was a formal institutional support, a system to address the infrastructural requirements, a formal protocol for referring patients to the clinic, and a free or subsidized testing.

Any service first needs to be marketed to the clinicians. Their belief in the service, confidence about the quality, and necessity of the service towards better patient-care and support are all critical factors for the long-term success of any clinic.

At times, the patients do get confused about what to discuss with the counselor and which questions are to be answered by the clinician. They end up asking treatment-related questions to the counselor and vice versa. So, ideally the patient should have an easy and immediate access, if possible, to the clinician for alleviating any doubts which are not addressed by the counselor. The clinician should also be mindful to not overtly contradict the explanations or concepts provided by the counselor. Ideally the clinician and the counselor should work in tandem [6, 8].

Extra efforts are required for long-term follow-up of the patients. This requires better infrastructure, man-power, and funding.

The clinical utility of genetic testing coupled with counseling should be established by statistics and trials. Documenting the achievements of counseling by parameters like “improved recruitment rate of patients for genetic tests” and “patient satisfaction levels” will go a long way in garnering the much needed institutional support and other resources for making genetic counseling clinics an integral part of any facility providing oncologic service [9, 13].