Women with at least three sites of cellular atypia in breast tissue are nearly eight times more likely than average women to develop breast cancer, according to findings of a Mayo Clinic Cancer Center-led study of women with atypical hyperplasia. The findings are published in the July 1 issue of the Journal of Clinical Oncology.

Several previous studies have shown that atypical hyperplasia (also called atypia) in breast tissue is a major risk factor for breast cancer. Women who have a breast biopsy and are diagnosed with atypia are considered at high risk. Many are counseled to consider preventive medications such as tamoxifen or other risk-reducing approaches. However, questions remained from prior research on whether a positive family history further increases risk in women with atypia and for how long the increased risk in women with atypia lasts.

“The most commonly used tool for risk prediction in women with atypia is the Gail model, which may predict inaccurately because our study shows that family history does not change risk significantly in women with atypia,” says Amy Degnim, M.D., a Mayo Clinic surgeon and study author. “Our findings indicate that women with atypia have a higher absolute risk for breast cancer than previously estimated. This risk is 25 percent over 25 years and is much higher in women with multiple areas of atypia and calcification.” The Gail model predicts risk by using 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.

While the Mayo Clinic study found that family history did not further increase risk, age at diagnosis of atypia did affect risk, with younger women (under age 45) more than twice as likely to develop breast cancer compared to women diagnosed with atypia after 55. The number of areas of atypical hyperplasia was significant as well. With one area of atypia, breast cancer risk was 2.3-fold compared to the general population; this risk more than doubled when two sites were found and increased to nearly eightfold as sites increased to three or more. The group of women with the highest risk had three or more areas of atypia and calcification - with a 10.4-fold risk over the general population.

“With the ability to stratify the risk of breast cancer in women with atypia, we can have more informed discussions with our patients regarding their personal risk,” says Dr. Degnim. “This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments.”

These findings resulted from reviewing the records of 331 women with atypia identified within the Mayo cohort of 9,376 women who had benign breast biopsies surgically obtained between 1967 and 1991. More than half (55.9 percent) of the women were over age 55 when diagnosed with atypia, and 42.9 percent had a family history of breast cancer. The majority (68.6 percent) of women showed calcification in the biopsy tissue, and 40 percent had multiple sites of atypical hyperplasia.

The American Cancer Society reports that more than 240,000 women will be diagnosed in the United States this year with breast cancer, and more than 40,000 will die from it. Dr. Degnim and her fellow researchers have been working to better understand the steps that precede breast cancer and which of them can be recognized in benign breast tissue. The current study contributes to Mayo’s emerging model that seeks to define every woman’s risk more precisely and to tailor screening and risk-reduction measures to women depending on their individual risks.

Other Mayo researchers included senior author Lynn Hartmann, M.D.; Marlene Frost, Ph.D.; Robert Vierkant; Shaun Maloney; V. Shane Pankratz, Ph.D.; Piet de Groen, M.D.; Wilma Lingle, Ph.D.; Karthik Ghosh, M.D.; Lois Penheiter; L. Joseph Melton III, M.D.; and Carol Reynolds, M.D. Collaborators from other institutions included Daniel Visscher, M.D., University of Michigan; Hal Berman, M.D. and Thea Tlsty, Ph.D., University of California, San Francisco; and Thomas Sellers, M.D., Ph.D., H. Lee Moffitt Cancer and Research Institute, Tampa, Fla.

The research was supported in part by a Department of Defense Center of Excellence Grant, the Susan G. Komen Breast Cancer Foundation, the Breast Cancer Research Foundation, and the Fred C. and Katherine B. Andersen Foundation.

Source: Mayo Clinic