For Families of Children with Cancer, A New Focus on Hereditary Risk

Key Takeaways:

  • Genetic counselors help families navigate hereditary cancer risk, prevention, and early detection.
    The Pediatric Cancer Genetic Risk Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center offers every patient family the opportunity to meet with a genetic counselor.

Widespread testing of pediatric tumors has confirmed a long-held suspicion: far more of them have hereditary roots than was once thought.

Physicians and researchers now estimate that at least 10% of cancers in children and adolescents, and probably many more, are linked to hereditary genetic mutations that increase cancer risk. The findings have changed the way young people at risk for cancer are monitored for the disease and expanded the role of genetic counseling for family members who also might be at risk.   

At Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, the family of every patient diagnosed with a solid tumor, brain tumor, or hematologic malignancy has the opportunity to meet with a genetic counselor. The counselor will draw a medical family tree to look for patterns of cancer within its branches and discuss the kinds of questions that genetic testing can help answer. If the family decides to go ahead with testing and the test reveals a mutation in a hereditary cancer-risk gene, the counselor can discuss what this might mean for other members of the family and what they can do to minimize their risk.

“The need for a program for families with heredity risk has long been recognized by Dana-Farber’s Cancer Genetics and Prevention Program for adults,” says Junne Kamihara, MD, PhD, co-director of the Pediatric Cancer Genetic Risk Program at Dana-Farber/Boston Children’s. “As testing of childhood tumors for genetic abnormalities increased, it became clear that such a program can benefit the families of pediatric patients as well.

“By identifying children and other family members with an inherited predisposition to cancer, we can follow them closely over the long term — a journey we feel privileged to take alongside families,” she continues. “The hope is that, if a child does develop cancer, we can catch it at its earliest stages, when it’s often easiest to treat.”

Junne Kamihara, MD, PhD.

The type of testing that can reveal a hereditary risk of cancer is known as germline testing. It involves analyzing the DNA in a person’s normal, healthy cells — often, blood cells — for mutations or other abnormalities associated with cancer. This type of testing differs from somatic testing, which looks for mutations specifically within tumor tissue.

At Dana-Farber/Boston Children’s, every patient with a solid tumor can have his or her tumor tissue analyzed for hundreds of somatic mutations as part of the Profile project. In many cases, mutations uncovered in these tests provide clues as to whether the patient carries certain germline mutations. In the most recent fiscal year, solid tumors from more than 1,000 pediatric patients underwent genetic testing at Dana-Farber/Boston Children’s.

Researchers have identified more than 100 genes that, if present in an abnormal form in a person’s germline, may increase the risk of certain cancers. Two examples:

  • RB1, which carries of high risk of a cancer of the eye. “If we have information that a parent harbors this mutation, we screen for this cancer as soon as a baby is born, or even before,” Kamihara says. About 20% of infants carrying this mutation go on to develop other cancers, including bone cancers and soft tissue sarcomas later in life. An even higher percentage may be at risk of developing a sarcoma if they had previous treatment with radiation therapy.
  • TP53, which is associated with Li-Fraumeni syndrome, a condition linked to a wide range of cancers, including bone and soft tissue sarcomas, adrenal cortical carcinomas, young-onset breast cancer, brain cancer, leukemia, and others.

Coming to terms with risk

Genetic counselors help families make sense of testing results and understand its potential impact on their lives and how they can protect themselves. Discussions often cover the uncertainties involved in genetic testing.

Doctors know, for example, that people born with a specific mutation are at heightened risk for certain cancers at various stages of life, but which cancer a particular individual may develop, and when, can’t be foreseen.

“Ultimately, the family wants to know whether their child will develop another cancer and when — and what type of cancer it will be,” says Jaclyn Schienda, ScM, CGC, the lead genetic counselor at the Pediatric Cancer Genetic Risk Program. “We explain that each condition is associated with different cancers and a different levels of risk, even within the same family. We talk about the different types of cancer linked to their condition and what symptoms to watch for. Our goal is to help the family adjust to living with risk without making it the predominant focus of their life.”

Conversations with young patients and their siblings are conducted at an age-appropriate level.

“For children who carry a mutation but haven’t had cancer, we spend a lot of time assuring them that they’re healthy now and our job is to keep them healthy,” Schienda states.

Multi-disciplinary approach

In addition to oncologists and genetic counselors, the Pediatric Cancer Genetic Risk Program includes nurse practitioners, and psychosocial specialists to work with patients and families. The program also supports research studies, including one led by Jennifer Mack, MD, MPH, on how to communicate the finding of a cancer risk to adolescents and young adults, and one led by Yana Pikman, MD, that involves genetically profiling patients’ leukemias to learn more about their cancers and how to treat them.

 “Our commitment to providing patients with the knowledge, support, and longitudinal cancer surveillance they need is a unique aspect of our program,” says Jessica Pollard, MD, who manages children with leukemia or lymphoma who possess an underlying heritable cancer risk. “We are optimistic that programs like ours will help improve outcomes for children identified with heritable risk for malignancies.”