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Researchers and patients join forces against Li-Fraumeni syndrome

  • John Berkeley's family has endured multiple cancers, some at a very early age. But as testing has revealed, bad luck is not to blame.

    Berkeley, his brother, and his father inherited a very rare condition conferring an extremely high risk of cancer — sometimes several tumors over a lifetime. The cause is a rare mutation in the TP53 gene, a master gene that normally suppresses cancer development.

    "The whole family went to Dana-Farber," recalls Berkeley, now 41 and in good health. "We were told that my father, my brother, and I had the gene for Li-Fraumeni syndrome. We took it with a grain of salt — we were, like, 'Hey, we beat cancer before, we'll get through it.'"

    The Berkeleys are one of about 60 Li-Fraumeni syndrome families followed in Dana-Farber's Cancer Genetics and Prevention Program, headed by Judy Garber, MD, MPH. The program provides counseling about reproductive options, which is critical since each child of a parent who carries the altered TP53 gene has a 50 percent risk of inheriting the mutant gene.

    Li-Fraumeni Syndrome raises a patient's lifetime cancer risk to as high as 85 percent — and half of cases are diagnosed before age 30.

    "I have a patient who's on her sixth cancer — but at least she has survived all the others," says Garber.

    Only about 400 Li-Fraumeni syndrome-affected families have been identified in the United States, along with an unknown number who haven't been diagnosed.

    Cancers typically diagnosed in Li-Fraumeni syndrome patients include breast cancer, soft tissue sarcomas, osteosarcoma, brain tumors, acute leukemia, and adrenal cortical carcinoma. Recently, the list has been expanded to include colon cancer and stomach cancer, following discoveries by Dana-Farber researchers Sapna Syngal, MD, MPH, Serena Masciari, MD, Garber, and others.

    The top priority for researchers and patients is to develop screening methods to detect cancers in their earliest, most treatable stages.

    "If we could identify all the families and have an effective way of screening their whole body, that would be ideal," says Syngal, clinical director of the Cancer Genetics and Prevention Program.

    In an encouraging study published in 2008 by Masciari, Garber, Syngal, and other Dana-Farber physician-scientists, examination with PET-CT scanning detected three cancers in 15 asymptomatic Li-Fraumeni syndrome patients. Turning to methods that don't expose patients to radiation, the Dana-Farber scientists are now testing full-body MRI scans and working toward a national study.

    In addition, Garber is pursuing leads suggesting that breast cancers in Li-Fraumeni syndrome tend to be the type that can be effectively treated by a targeted drug, Herceptin. "Our hope is that these patients should do better in the future," she says.

    Another boost for the Li-Fraumeni syndrome community was a meeting last November in Washington, DC, that brought together about 80 Li-Fraumeni syndrome patients for the first time with a group of physician-scientists doing research on the syndrome.

    The meeting also served as a launch pad for a national Li-Fraumeni syndrome support organization. Berkeley spearheaded and is president of the new Li-Fraumeni Syndrome Association.

    "The main thing we want to say is that you're not the only one out there with this; we're all in this together," Berkeley says. "Our goal is to reach the entire world, and bring all the patients with Li-Fraumeni syndrome to one location for support, advocacy, and medical information."