Clue to the Origin of Sporadic Breast Tumors

Researchers have detected genetic aberrations in healthy tissue of some breast cancer patients who do not seem to possess a genetic predisposition to the cancer. The finding, reported in the current issue of Science, could someday help scientists understand what causes nonhereditary breast tumors, which account for about 90% of all cases, as well as providing guidance for breast cancer treatment.

A team led by cancer researcher Helene Smith of the California Pacific Medical Center in San Francisco looked for a particular type of genetic abnormality called loss of heterozygosity (LOH)--the disappearance of an allele, or copy of a gene from either parent--in tissue samples adjacent to tumors in 30 breast cancer patients. They chose this abnormality, Smith says, because deletion or inactivation of tumor-suppressor genes is thought to contribute to many kinds of cancers, and LOH is a characteristic sign that a suppressor gene has been lost.

The search was successful. Smith's team found LOH in normal tissue samples from 30 patients, including six in which the same allele on chromosome 3 was missing--an indication that this region of the genome might be missing an important tumor-suppressor gene. "These are very interesting findings," says pathologist Craig Allred of the University of Texas, San Antonio. "It's certainly a new twist for research, and we're scratching our heads a bit. We have to rethink some fundamentals now that they've found abnormalities in tissue previously thought of as normal."

The origins of the LOH remain a mystery. "Since these genetic aberrations are not inherited, we must look elsewhere for causes, including diet, early exposure to radiation, or perhaps environmental pollutants," Smith says.

But whatever the cause of the LOH, the discovery could have implications for breast cancer treatment, Smith says: "Once the lump is found, sampling surrounding tissue during a lumpectomy could help identify women who will have local recurrences of breast cancer and could indicate which would benefit from more aggressive treatment." She adds, however, that before this approach can be tried in the clinic, much more work will be needed to establish the prognostic value of the findings.