Women with atypical hyperplasia at higher risk of breast cancer

Volume 4, Issue 1, 2015


Findings may spur recommendations for screening MRI, medications.

Photograph of Lynn C. Hartmann, M.D.

Lynn C. Hartmann, M.D.

Women with atypical hyperplasia of the breast have a higher risk of developing breast cancer than previously thought, a Mayo Clinic Cancer Center study has found — findings that could have implications for breast cancer screening and prevention.

Results of the study were published in a special report on breast cancer in the New England Journal of Medicine.

Atypical hyperplasia of the breast, also known as atypia, is a precancerous condition found in about one-tenth of the over 1 million breast biopsies with benign findings performed annually in the United States.

Atypia lesions contain breast cells that are beginning to grow out of control (hyperplasia) and cluster into abnormal patterns (atypical). Although atypia lesions are considered benign, they exhibit some of the early features of cancer because of their appearance and genetic changes.

Data from hundreds of women with these benign atypia lesions indicate that their absolute risk of developing breast cancer grows by more than 1 percent a year.

The study found that after five years, 7 percent of these women had developed breast cancer. After 10 years, that number had increased to 13 percent, and after 25 years, to 30 percent.

These data place the more than 100,000 women diagnosed each year with atypical hyperplasia into a high-risk category, where they may be more likely to benefit from intense screening and use of medications to reduce risk.

"By providing better risk prediction for this group, we can tailor a woman's clinical care to her individual level of risk," said Lynn C. Hartmann, M.D., an oncologist at the Mayo Clinic Cancer Center and lead author of the study. "We need to do more for this population of women who are at higher risk, such as providing the option of MRI screenings in addition to mammograms and encouraging consideration of anti-estrogen therapies that could reduce their risk of developing cancer."

Previous research has shown that a woman with atypia has a fourfold to fivefold increased relative risk — meaning that she is four to five times more likely to develop breast cancer than is a woman who doesn't have these lesions. But few studies have had the patient numbers and follow-up time to report the absolute risk — the chance that a woman will develop breast cancer over a certain period of time.

To clearly define absolute risk, the Mayo Clinic team followed 698 women with atypia who had biopsies at Mayo Clinic between 1967 and 2001. The researchers reviewed pathology and medical records and used patient follow-up questionnaires to determine which women developed breast cancer and when.

The researchers found that after an average follow up of 12.5 years, 143 women had developed breast cancer.

Importantly, the Mayo Clinic findings were validated by researchers at Vanderbilt University using biopsies from a separate cohort of women with atypia. Both data sets revealed that at 25 years after biopsy, 25 to 30 percent of these women had developed breast cancer.

The Mayo Clinic team had previously showed that two common statistical breast cancer risk prediction models — the BCRAT and the IBIS models — performed poorly in women with atypical hyperplasia, underscoring the need to provide alternative approaches for predicting risk in this population.

"Instead of relying on a statistical model, our study provides actual data of breast cancer cases that occurred in a population of women with atypia. These absolute risk data are preferable to a hypothetical model," said Amy C. Degnim, M.D., co-lead author of the study and a breast surgeon at the Mayo Clinic Cancer Center.

Based on these results, the research team recommends that women with atypical hyperplasia be recognized as having a significantly increased lifetime risk of breast cancer. This means they should be possible candidates for screening MRI and medications.

Anti-estrogen medications such as tamoxifen have already been tested in clinical trials in women with atypia and shown to lower the risk of breast cancer by 50 percent or more. Yet many women with atypia don't take these kinds of medications, in part because they and their physicians have not had solid estimates of their breast cancer risk to guide them.