MODULATION OF BCL-2 AND KI-67 EXPRESSION IN ESTROGEN RECEPTOR-POSITIVE HUMAN BREAST-CANCER BY TAMOXIFEN

The expression of the bcl-2 proto-oncogene, which is associated with p rolonged cell survival and prevention of programmed cell death, was in vestigated in human primary breast carcinomas prior to and following e ndocrine therapy with the anti-oestrogen, tamoxifen. Using the BCL-2-1 00 antibody, a 26-kD protein was detected by western immunoblot in the cytosols of oestrogen receptor (ER)+ve human breast cancers. In a cro ss-sectional study, the immunohistochemical expression of Bcl-2 was ob served in 32% of invasive breast cancers, but in 65% of tumours treate d with tamoxifen (P = 0.009). There was a significant association of B cl-2 with ER status, with 64% of untreated and 88% of tamoxifen-treate d Bcl-2-positive tumours being ER+ve. A significantly lower Ki-67 scor e was found in tamoxifen-treated tumours which were Bcl-2-positive com pared with Bcl-2-negative (9.3 versus 24.6%, P = 0.01). In a separate series of sequential Trucut biopsies from 18 patients, the frequency o f Bcl-2 expression was increased in ER+ve tumours from 3/12 to 8/11 fo llowing tamoxifen (P = 0.04). This was also associated with a signific ant reduction in mean Ki-67 score from 32 to 12% (P = 0.0004). The obs ervations from this study clearly indicate that Bcl-2 in human breast cancer is associated with ER status, and that expression is enhanced i n ER+ve tumours following tamoxifen, in association with reduced cell proliferation.