Change in oestrogen receptor expression and function in tamoxifen-resistant breast cancer

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Abstract
Loss of oestrogen-receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. In 72 paired biopsies the immunohistochemical expression of ERs was reduced from 51% before tamoxifen treatment to 29% at progression or relapse, with a reduction in mean H-score from 90 to 61 (Pt-test). However, there was no significant change in progesterone receptor (PgR) or pS2 expression, markers of ER function. Tumours which developed acquired resistance after primary tamoxifen treatment frequently remained ER+ve at relapse (61%) and continued to express PgR or pS2. In contrast, those which progressed with de novo resistance were all ER−ve, although 6 of these tumours expressed high levels of PgR and/or pS2. In tumours which recurred during adjuvant tamoxifen therapy, the frequency and quantitative level both of ERs and of PgR were significantly reduced. These data imply that separate mechanisms of tamoxifen resistance may exist in these clinical subgroups.

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