Background Predicated on its cytologic features and its co-occurrence with atypical

Background Predicated on its cytologic features and its co-occurrence with atypical hyperplasia and breast cancer flat epithelial atypia (FEA) has been proposed as a precursor lesion on the pathway to breast OSU-03012 cancer development. Epidemiology and End Results registry. Results FEA was identified in 282 women (2.4%); 130 had associated AH (46%) and 152 (54%) were classified as proliferative disease without atypia (PDWA). With median follow-up of 16.8 years the SIR for breast cancer in AH + FEA was 4.74 (95% CI: 3.17-6.81) versus 4.23 (3.44-5.13) for AH without FEA (p=0.59). The SIR for PDWA + FEA was 2.04 (95% CI: 1.23-3.19) versus 1.90 (1.72-2.09) for PDWA without FEA (p=0.76). Conclusions FEA is an uncommon finding in women with BBD. FEA does not convey independent risk of breast cancer beyond that of the associated PDWA or AH. Igf1 Keywords: OSU-03012 atypia breast cancer flat epithelial atypia columnar cell lesion of breast proliferative disease without atypia Introduction Flat epithelial atypia (FEA) is a benign proliferative breast lesion characterized by columnar cell changes with cytologic atypia. It is often referred to as an “atypical” lesion or a high-risk lesion. However FEA is distinct from classical atypical hyperplasia (that includes atypical ductal hyperplasia [ADH] and atypical lobular hyperplasia [ALH]). Atypical hyperplasia (AH) is a long-established premalignant lesion with a four-fold increased risk of later breast cancer which demonstrates not only cytologic atypia but also architectural abnormalities.1-4 FEA is the most advanced subset of a group of breast lesions called “columnar cell alteration of lobules” which exhibit abnormal polarization of luminal epithelium.5 Some molecular data support a possible role for FEA as a precursor lesion in a pathway of low-grade malignancy.6-8 However the association between FEA and subsequent breast cancer (BC) risk remains undefined. Thus there is significant uncertainty regarding the optimal clinical management of women with FEA.9-11 Using the Mayo Clinic Benign Breast Disease Cohort our primary goal was to investigate the independent BC risk associated with FEA by evaluating its impact on BC risk within well-established risk groups of benign breast disease- 1) AH plus coexistent FEA versus AH without FEA and 2) proliferative disease plus coexistent FEA versus proliferative disease without FEA. We explored the impact of FEA on BC risk in relation to other BC risk factors such as family history of BC patient’s age at biopsy and associated lobular involution. Also OSU-03012 we characterized the breast cancers that occurred among women with FEA in order to address the low-grade malignancy hypothesis. Materials and Methods Study Population The Mayo BBD Cohort includes 13 434 women ages 18-85 who had a breast biopsy with benign findings between January 1967 and December 2001.4 In this report we focused on the 11 591 women who had an excisional breast biopsy or needle biopsy followed by excision for several reasons. Excision of lesions with atypia has been and remains the OSU-03012 current standard of practice.12 Furthermore inclusion of women with core-only biopsies would introduce selection bias and could result in missed cancers that would alter results on cumulative cancer risk.13 Demographic information clinical findings family history follow-up and BC events (both invasive cancer and ductal carcinoma in situ) were obtained from the patients’ medical records Mayo Tumor Registry and a study-specific questionnaire. We categorized the family history of BC into three groups: 1) strong = at least 1 first degree relative with BC before the age of 50 years; or 2 or more relatives with BC with at least 1 being a first degree relative; 2) weak = any family history less than the definition of strong; and 3) none = no family history of BC. The study protocol including patient contact and follow-up methods on ascertainment of later breast cancers was approved by the Mayo Clinic Institutional Review Board with methods previously described.1 Breast Histology Original archived slides of breast biopsy tissues (hematoxylin and eosin stain) for the entire cohort were characterized with an independent re-review by a single breast pathologist (DWV) who was blinded to both the original diagnosis and later patient outcomes. Histologic findings of the breast biopsy tissues were recorded and classified using Dupont and Page criteria2 into the three primary histologic groups of benign breast disease: nonproliferative disease (NP) proliferative.