Abnormal regulation of the oestrogen receptor in benign breast lesions

Background-In normal breast tissue the oestrogen receptor (ER) and the prol iferation associated antigen Ki67 are negatively associated, indicating tha t ER+ cells are non-dividing, or that the receptor is downregulated as cell s enter cycle. This relation is completely or partially lost in many ER+ br east cancers and in in situ proliferations associated with an increased can cer risk, where coexpression of the two markers is often found. Aims-To determine whether similar changes can be identified in other risk a ssociated breast lesions. Patients/Methods-Paraffin wax blocks from 12 cases of lactational change, 2 1 apocrine metaplasias, 22 duct ectasias, 20 sclerosing adenosis, 20 fibroa denomas, 19 phyllodes tumours, 20 radial scars, 21 papillomas (15 solitary and six multiple), IS gynaecomastias, and nine postmortem male breast tissu es were retrieved. Immunohistochemistry was used to determine the expressio n of ER and dual labelling immunofluorescence was used to detect cells expr essing both ER and Ki67. Results-Increased numbers of ER+ cells were seen in sclerosing adenosis, ra dial scars, papillomas, fibroadenomas, and phyllodes tumours but not in apo crine cysts (where no ER+ cells were detected) or duct ectasia (where norma l numbers were found). As in the normal breast, the proportion of ER+ cells increased with age in all lesions with the exception of fibroadenomas. Coe xpression of ER and Ki67 was found in an increased proportion of cells of a ll risk associated lesions studied. ER+ cells were less likely to be dividi ng than ER- cells in all cases, although this was significant only for scle rosing adenosis. The data on sclerosing adenosis, radial scars, papillomas, and fibroadenomas are comparable with those reported previously in hyperpl asia of usual type, whereas those in duct ectasia are similar to those of t he normal breast. The findings in all lesions, however, differed from those in ductal carcinoma in situ, where proportions of ER+ and ER+/Ki67+ cells are higher and the relation between ER+ cell numbers and age is lost. Thus, the nature and degree of dysregulation of ER in benign breast lesions is b roadly in accordance with the degree of risk of developing breast cancer wi th which they are associated. In gynaecomastia, the proportions of ER+ and ER+/Ki67+ cells were comparable with those seen in benign female breast les ions, but changes with age were not observed. However, the changes in gynae comastia were similar to those seen in normal male breast. Conclusion-These findings are in keeping with the contention that the disso ciation of ER and Ki67 expression is a very early change in the pathway to many breast cancers. However, this change might only have preneoplastic imp ortance in the hormonal milieu of the female breast.