Oestrogen receptor expression in the normal and pre-cancerous breast

As oestrogen is associated with most of the epidemiological risk factors fo r breast cancer, the number and distribution of oestrogen receptor positive (ER +) cells could have a bearing on the development of the disease. ER cells were thus studied in the normal breast and in the spectrum of in situ proliferations which range from non-atypical hyperplasia to in situ carcin oma and are associated with different levels of risk for developing breast cancer. In the normal pre-menopausal breast, ER + cells comprised the minor ity and were distributed singly, being surrounded by oestrogen receptor neg ative (ER -)cells, ER + cells showed a statistically significant increase w ith age, reaching a plateau after the menopause, and the increase was assoc iated with a tendency for positive cells to become contiguous in patches of variable size. A small proportion of lobules showing involutional change c omprised over 90 per cent ER + cells, The significance of this feature is n ot dear but no evidence mas found that it was pre-cancerous. The percentage of ER + cells was slightly increased in hyperplasia of usual type (non-aty pical hyperplasia, HUT) and the relationship to age was maintained. The sta ining pattern was variable; in some lesions ER + cells were surrounded by E R - cells whereas in others there mere contiguous groups of positive cells sometimes accounting for more than 90 per cent of cells in the lesion. In c ontrast, all cases of atypical ductal hyperplasia (ADH), lobular in situ ne oplasia (LIN) and ductal carcinoma in situ (DCIS) exhibited positivity of c ontiguous cells accounting for the majority in the lesions. Furthermore, th e relationship between ER + cell numbers and age was lost in these lesions, indicating autonomy of ER expression or of proliferation of cells ex-press ing the receptor, It is hypothesized that this dysregulation of receptor ex pression or of ER + cell numbers at the ADH stage may be the precursor of a bnormal expression of cyclins and other cell cycle control proteins which h ave been shown first to appear in DCIS, Copyright (C) 1999 John Wiley & Son s, Ltd.