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The potential synergism of sequential combinations of tamoxifen (TMX) or estradiol benzoate (E2B) with medroxyprogesterone acetate (MPA) in inhibiting the growth of 7.12-dimethylbenz(a)anthracene(DMBA) - induced rat mammary tumors has been investigated. In addition, the effect of TMX and E2B on estrogen and progesterone receptors' (ERs and PgRs) synthesis has been evaluated in the attempt to elucidate possible mechanisms involved. Previous treatment both with TMX and E2B has been shown to strongly enhance the antitumor activity of MPA. A priming on PgR synthesis has been observed only after E2B administration, TMX producing a sharp decrease in PgR levels. It is concluded that, while the priming action exerted by E2B on PgRs might explain the potentiating effect shown by E2B on MPA activity, the synergism observed between TMX and MPA should be explained on an extrareceptorial basis, an induction on PgR synthesis by TMX not being evident at the dosage and priming time employed in this study.

Intracranial metastases represent 7-17% of all brain tumours, their incidence at autopsy varying between 5.8 and 22% in different series. The neoplasms most commonly metastasizing to the brain are those of lung, breast, renal and skin (melanoma) origin. In two-thirds of cases, intracranial metastases are located within the brain parenchyma, while the remaining third involves the pachymeningeal envelopes. Leptomeningeal metastases are rare and develop mainly from leukemia, lymphomas and breast carcinoma. The route of spread to the central nervous system is usually hematogenous but occasionally direct involvement from adjacent bone or pachymeningeal metastases can occur. Median survival from clinical presentation usually doesn't exceed a few months. However brain metastases are the cause of death only in about 15% of patients. This is probably due because they occur late in the course of the natural history of the disease, when metastatic deposits in other viable organs have already developed. Due to this reason, systematic assessment of metastases to the brain is not advisable in all patients but it should be restricted to symptomatic patients and to asymptomatic patients affected by small cell carcinoma and adenocarcinoma of the lung, who could benefit from prophylactic brain irradiation. In symptomatic patients, plain skull X-ray, electroencephalography and computed tomography represent appropriate diagnostic tools to provide accurate informations about number, size, site and morphological characteristics of brain metastases.