A study reported by Hartmann et al. of the Mayo Clinic showed that breast biopsies with atypical hyperplasia were diagnosed as benign, a diagnosis that masked the risk of the lesion. Women with atypical hyperplasia diagnosed as “benign” on breast biopsy have a much higher risk of developing future breast cancer than previously thought. The researchers subdivided 698 cases of atypical hyperplasia (also known as heterogeneous hyperplasia) of the breast. Over 25 years of follow-up, 143 cases developed breast cancer, with a cumulative incidence of breast cancer of 30 percent, 81 percent of which were invasive and 19 percent were ductal breast cancer in situ. The cumulative incidence of breast cancer increased over time for atypical hyperplasia biopsies. 6.6% at 5 years, 12.6% at 10 years, 19.4% at 15 years, 23.1% at 20 years, and 30.3% at 25 years, compared with 8% in the control group. The investigators also analyzed the number of lesions and the cancer rate: at 15 years of observation, the cancer rate was 14.2% for one atypical hyperplasia lesion, 23.3% for two lesions, and 34.4% for three or more lesions. Atypical hyperplasia can be divided into two categories, namely ductal atypical hyperplasia and lobular atypical hyperplasia, both of which have a similar incidence and probability of future breast cancer. The investigators emphasize that the higher cumulative incidence of breast cancer is not widely recognized and accepted, so in many cases women with atypical hyperplasia are overlooked, and this population has a higher risk of breast cancer. Each year, 1 million women in the United States receive a diagnosis of benign breast biopsy results, and atypical hyperplasia accounts for 10% of these benign diagnoses. The relatively high risk of breast cancer in atypical hyperplasia compared to other benign lesions has been known for decades, although it is only recently that the absolute breast cancer risk of atypical hyperplasia has been explored. In addition to the 30% breast cancer incidence reported by the researchers, another unpublished cohort study yielded a 27.5% breast cancer incidence. Clinicians can now apply these absolute risk data rather than using risk prediction models, which have generally not been validated in cases of atypical hyperplasia. The investigators suggest that patients with atypical hyperplasia should be monitored more closely and that patients with atypical hyperplasia should receive annual breast MRI in addition to annual mammograms. Chemopreventive medications, such as selective estrogen receptor modulators and aromatase inhibitors, which have been shown to benefit women with atypical hyperplasia, may also be considered. However, these prophylactic measures have both advantages and disadvantages. For example, the main risk of applying estrogen receptor modulators is venous thrombosis, and the application of tamoxifen increases the risk of endometrial cancer. The American Society of Clinical Oncology (ASCO) guidelines state that chemoprevention should be considered for a 5-year predicted absolute breast cancer risk higher than 1.7%, and it is clear that the risk of breast cancer in patients with atypical hyperplasia meets this criterion.