Résumé
This study was undertaken to investigate the mechanism[s] underlying the use of tamoxifen [TAM], a selective estrogen receptor modulator [SERM], in estrogen receptor [ER] negative breast cancer and to assess the role of TAM on lymphokine activated killer [LAK] cells reactive to autologous breast cancer cells. Twenty female breast cancer patients attending the outpatient clinic of the Medical Research Institute were enrolled in this study. All patients had modified radical mastectomy. Pieces of fresh breast tumor cells and their in vitro generated autologous LAK were treated with different doses of TAM prior to or during the cytotoxicity assay. Estrogen receptors were measured using the enzyme immunoassay kit. Treatment of effector cells with TAM did not affect their lytic function against their autologous breast cancer cells, irrespective of their ER state. However, TAM pretreatment of ER positive breast cancer cells resulted in their significant lysis by their autologous LAK cells. The degree of enhancement was directly proportional to the dose of TAM. On the other hand, pretreatment of ER negative breast cancer cells with TAM did not affect their lytic response to autologous LAK cells. An enhanced cytolytic effect was only observed for ER negative breast cancer cells when TAM was directly added to the cytotoxicity assay, indicating an indirect mode of action through the release of mediators. The data provide an evidence of a dual mechanism of action of TAM, one direct, which is evident against ER positive cancer cells while the other is indirect through the release of mediators. This might explain the usefulness of selective estrogen receptor modulators in ER negative breast cancer patients