Prostacyclin and thromboxane in breast cancer: Relationship between steroid receptor status and medroxyprogesterone acetate

Abstract

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.