Gene defect may yield cancer prognosis.

Following a routine mammogram and biopsy of a suspect area in her breast, a 55-year-old woman learns she has breast cancer. After removing the tumor, her doctor tells her the cancer was at a very early stage and has not spread, so she stands a good chance of beating the disease.

Nonetheless, the cancer quickly and aggressively reappears.

Physicians caring for breast cancer patients know this scenario only too well: Cancers can recur with a vengeance, even when all indicators give a good prognosis.

Researchers from Minnesota and California have found that breast cancer tumors with mutations in the p53 gene recur more quickly, and prove more deadly, than tumors with normal copies of the gene. This finding could one day help "physicians identify patients who, despite lack of conventional indicators of poor prognosis, are at high risk of early recurrence and death," says study collaborator Arndt Hartmann of the Mayo Clinic and Foundation in Rochester, Minn.

Tumors with a mutated p53 gene produce an inactive version of the p53 tumor suppressor protein. Scientists suspected that such tumors could be very aggressive. In fact, previous studies have indicated that tumors with p53 mutations tend to resist radiation treatment and many anticancer drugs.

Hartmann and his colleagues followed 97 women with breast cancer for an average of 2 years. The researchers compared recurrence and survival rates to conventional indicators, such as the spread of tumors to lymph nodes and the absence of estrogen receptors, as well as to the presence of p53 mutations. Mutations provided the only reliable predictor of poor prognosis.

Hartmann points out that the researchers need to confirm their findings in a much larger group of patients before p53 mutations should be used to determine prognosis.