Living with Li-Fraumeni Syndrome is Using Knowledge as Power

Breast cancer survivor Jennifer Perry is at high risk of additional cancers during her lifetime because she carries an inherited mutation for Li-Fraumeni syndrome (LFS). But experts at the new Li-Fraumeni Syndrome and TP53+ Center at Dana-Farber Cancer Institute can help her manage that risk.

While there is no treatment for LFS — a familial cancer predisposition syndrome thought to affect as many as 1 in 5,500 people — Perry’s care team is providing her and other patients with a combination of personalized cancer risk management plans and social support. Under that guidance, Perry can cope with LFS and even thrive as a patient advocate.

“As stressful as it is, I would rather find something early and deal with it,” says Perry, 52. “Knowledge is power.”

Jennifer Perry.

An inherited mutation in a tumor-suppressor gene called TP53 robs individuals with LFS of a cellular mechanism that normally services to prevent cancers from developing. Multi-generational families diagnosed as having Li-Fraumeni syndrome typically have many members diagnosed with different cancers, often early in life.

Some individuals have been found to have a mutated TP53 gene, increasing their cancer risk, but their family histories don’t show the typical clustering of cancer cases seen in Li-Fraumeni syndrome. To serve and support people in either of these categories, Dana-Farber developed the Li-Fraumeni Syndrome and TP53 Center. It is the first comprehensive, multidisciplinary center in the world that specializes in coordinating the care of people with LFS and TP53 mutations. The center also provides reproductive counseling and psychological and social support for patients and their families.

Managing risk

People with Li-Fraumeni syndrome, or LFS, are prone to developing an unpredictable variety of cancers at any time during their life, often at a young age. Typical estimates of risk are about 50 percent of developing cancer by age 40 and up to 90 percent by age 60. These cancers can range from bone or soft-tissue sarcomas to breast cancer, brain tumors, adrenal cortical carcinoma, gastrointestinal cancers, or leukemia.

“In the early days, we estimated that the lifetime risk of cancer was almost 100 percent, but as testing is offered more broadly, we’ve learned that isn’t the case at all — some families won’t have as high a risk,” says Judy Garber, MD, director of the Li-Fraumeni and TP53 center and director of Dana-Farber’s Center for Cancer Genetics and Prevention.

Any child of someone with LFS has a 50-50 chance of inheriting the LFS mutation. One of Perry’s two sisters has LFS, as do both of her daughters, who are 25 and 16.

Like her mother, Perry was diagnosed with breast cancer at age 36. Although she knew that a lot of her family members had been treated for cancer, it wasn’t until several years after her breast cancer diagnosis that she learned she had Li-Fraumeni syndrome as a result of genetic testing at Dana-Farber. (One of the two scientists for whom the syndrome is named, Frederick Li, MD, was a Dana-Farber researcher.)

Perry underwent a double mastectomy and other surgeries to remove tissue that might become cancerous. Today, she is on a regimen of annual skin cancer checks, periodic blood tests and gynecologic exams, and a colonoscopy every three years. Her physicians, including Garber, have told Perry to contact them if she experiences any unusual pains or symptoms.

Judy Garber, MD.

Cancer screening starts early

A difficult issue in families carrying the Li-Fraumeni mutation centers on the decision to test young children who have not been diagnosed with cancer, to determine if they have inherited the mutant TP53 gene. Perry’s daughters were 10 and 19 when she learned she had the Li-Fraumeni mutation.

“It was a challenge,” Perry recalls. “But I wanted to make sure I could protect them as much as possible” by having them learn their genetic status and undergoing appropriate screening, she says.

Because of the risk of early-onset cancers, exams and screening, such as breast MRI, mammograms, and colonoscopies, are recommended beginning in the early to mid-20s.

Perry has thrown herself into work aimed at raising awareness and providing support for other LFS patients and families. She is the cofounder and president of the Li-Fraumeni Syndrome Association (LFSA), which sponsors a conference every other year. The LFSA, besides sponsoring conferences, uses social media and one-to-one conversations to connect with patients and share resources. The LFSA has also organized events and conferences to support children and young adults.

She says she is extremely grateful for the support of Dana-Farber and especially Garber: “She’s been our guardian angel and an incredible mentor,” Perry says.

How does someone with LFS, living with such a relentless likelihood of cancer, avoid dwelling on the uncertain future? For Perry, it’s a combination of passions in her life — she’s a competitive equestrian — and helping other people, and keeping in mind, she says, “that Li-Fraumeni doesn’t define me.” She adds that having a support system is critical, along with “staying healthy — the healthier we stay, the better — exercise, hobbies, and things that make you feel great.”