Atypical Hyperplasia Risks Grow with the Number of Sites

ROCHESTER, Minn., June 29 -- Women with atypical hyperplasia in three or more places in the breast have a sharply increased risk of developing breast cancer, researchers here said.

Atypical hyperplasia -- also known as atypia -- is well known to increase the risk of breast cancer by about four times that faced by women who don't have the condition, according to Amy Degnim, M.D., of the Mayo Clinic.

But, as she and her colleagues reported in the July 1 issue of the Journal of Clinical Oncology, when atypia is seen in several places in the breast, the risk doubles to eight times.

Other factors tending to increase the risk are younger age at diagnosis and the presence of calcifications, the researchers said.

Their findings come from an analysis of 331 women with atypia -- members of the 9,376-strong Mayo Benign Breast Disease Cohort, who had breast biopsies from 1967 through 1991.

Followed for an average of 13.7 years, 66 developed breast cancer, the researchers reported. Compared to the general population, that works out to a risk ratio of 3.88, with a 95% confidence interval from 3.0 to 4.94 -- in close accord with previous estimates.

But the researchers also found:

• Family history did not appear to make a difference; the risks were much the same whether the women had a strong, weak, or negative family history of breast cancer.
• Women diagnosed at a younger age had significantly higher risk ratios compared to age-matched expected rates - 6.76 for those diagnosed younger than 45, 5.10 for those diagnosed from 45 through 55, and 2.87 for those diagnosed at an older age. The trend was significant at P=0.01.
• The risks increased with the number of foci of atypia - 2.33 for a single focus, 5.26 for two foci, and 7.97 for three or more. The trend was significant at P<0.001.
• A small number of women - 38 -- had both three or more foci and calcifications and their risk was 10.4 times that of the general population.

The analysis also showed that the relative risk of breast cancer for the group was elevated for several years, with 20-year and 25-year cumulative risks of 21% and 29%, respectively.

When the participants were stratified on the basis of the number of foci, the 25-year cumulative risks were 18% for a single focus, 45% for two foci, and 49% for three or more.

The value of the findings to clinicians lies in the ability to stratify risk, Dr. Degnim said.

"We can have more informed discussions with our patients regarding their personal risk," she said. "This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments."

The most commonly used tool to predict risk in women with atypia is the so-called Gail model, Dr. Degnim said, which used such factors as age at onset of menses, age at birth of first child, number of previous breast biopsies, presence of atypia, and number of close relatives with breast cancer.

But that model may not be accurate, she said, because the current study suggests that family history plays little or no role.