Expression of ERalpha and ERbeta in lobular carcinoma in situ

Oestrogen is a modulator of cell growth and differentiation in the breast. It mediates most of its function through members of the oestrogen receptor (ER) family, ERalpha and ERbeta. Lobular carcinoma in situ (LCIS) is a known risk factor for the development of breast cancer; however, the use of tamoxifen for prevention is based upon data for ER+ (ERalpha) LCIS associated with invasion, but limited data exist on the use of tamoxifen in cases of ER+ (ERalpha) LCIS occurring in the absence of invasive carcinoma. The aim of this study was to examine ER expression in LCIS to determine the relationship of ERalpha to ERbeta and, thereby, to determine whether it is of clinical value to measure ERbeta along with ERalpha.

Core biopsy specimens from 50 patients were examined retrospectively. Histology was reviewed and histological parameters were assessed. Formalin-fixed paraffin-embedded tissue was available for E-cadherin, ERalpha and ERbeta immunohistochemistry. The degree of ERalpha and ERbeta nuclear reactivity was quantified. The patients' mean age was 55 years. The mean follow-up duration was 48 months. All 50 cases of LCIS were E-cadherin-negative. All cases were ERalpha+ and ERbeta+. The staining intensity of ERbeta was strong and included staining of periductal stromal cells. The median percentage of cells immunoreactive for ERalpha was 75% and for ERbeta 70% (range 10% weak positive to 100% strong positive). There was a statistically significant relationship between ERbeta staining intensity and incidence of ipsilateral breast cancer (P = 0.010).

The presence and intensity of both stromal and glandular ERbeta immunoreactivity suggest that the action of oestrogen on LCIS is on both stromal and glandular cells. Future studies are needed to determine whether the presence of ERbeta in LCIS could be targeted to influence the treatment of this disease and perhaps alter its natural history.