Abstract Background: Fibroadenoma (FA) is a common benign breast lesion known to have a high incidence rate in younger women. There are controversial reports whether FA elevates the risk of developing breast cancers. In clinical practice, FA may be surgically removed due to multiple reasons making it complicated to study its impact on the development of breast cancers that have a higher incidence rate in older women. Fibroadenomatoid change (FAC), also known as fibroadenomatous hyperplasia, is an uncommon lesion with histologic features similar to that of FA but lacking well-defined borders and usually discovered incidentally on breast biopsy specimens. FAC is not surgically targeted. The Walter Reed Army Medical Center, through the Clinical Breast Care Project, has enrolled over 2000 subjects undergoing a biopsy; all the pathology was reviewed by a single pathologist. These subjects provide an opportunity to study the age-dependent pattern of FAC in different patient populations. Methods: Subjects were enrolled following IRB-approved protocols with data collected through two comprehensive questionnaires, a Core Questionnaire and a Pathology Checklist. A total of 1964 female subjects were identified for this study, including 1135 benign/atypical, 192 in situ, and 637 invasive cancer patients. Patients were divided into three age groups: <=45 years, 46–65 years, and >=66 years. Chi-Square test in the SAS was used for statistical analysis. Results: As shown in the table, FA occurrence rate decreases significantly with increasing age in benign disease patients. FAC, on the other hand, shows a significantly higher occurrence rate in middle-aged patients with benign findings, and this trend is retained in the invasive or in situ cancer populations. FAC rate is also significantly higher in patients with cancer (invasive, or invasive and in situ combined) compared to benign patients in each age group with p-values ranging from 0.0001 to 0.019 (not shown). Discussion: Our preliminary results suggest that FAC occurs more often in middle-aged patients. It's significantly lower occurrence in patients with benign findings may be partially explained by the fact that breast cancer patients undergo more extensive surgeries, thus providing more breast tissue for pathologic evaluation. Otherwise, the increased FAC rate may suggest its role as a risk factor for cancer development. Since FAC may be considered a miniature FA that is not surgically targeted, it may be used as a window for the study of FA on its impact in cancer development. Further study needs to be performed to explain why FA and FAC have different age-dependent patterns and whether FA or FAC is a risk factor for breast cancer development. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-03-06.