Originally published as JCO Early Release 10.1200/JCO.2006.09.0217 on June 11 2007

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Stratification of Breast Cancer Risk in Women With Atypia: A Mayo Cohort Study

Amy C. Degnim, Daniel W. Visscher, Hal K. Berman, Marlene H. Frost, Thomas A. Sellers, Robert A. Vierkant, Shaun D. Maloney, V. Shane Pankratz, Piet C. de Groen, Wilma L. Lingle, Karthik Ghosh, Lois Penheiter, Thea Tlsty, L. Joseph Melton, III, Carol A. Reynolds, Lynn C. Hartmann

From the Divisions of General Surgery, Anatomic Pathology, Medical Oncology, Biostatistics, Gastroenterology and Hepatology, Experimental Pathology, General Internal Medicine, and Epidemiology, Mayo Clinic College of Medicine, Rochester, MN; University of California, San Francisco, San Francisco, CA; and the H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Address reprint requests to Lynn C. Hartmann, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: hartmann.lynn{at}mayo.edu

Purpose Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed.

Patients and Methods Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time.

Results With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (< 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years.

Conclusion Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate "very high risk" status (> 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.

published online ahead of print at www.jco.org on June 11, 2007.

Supported by Department of Defense Center of Excellence Grant No. FEDDAMD17-02-1-0473-1, R01 CA46332, Susan G. Komen Breast Cancer Foundation Grant No. BCTR99-3152, the Breast Cancer Research Foundation, and the Andersen Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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