Assessment of five serum marker assays in patients with advanced breast cancer treated with medroxyprogesterone acetate.

This study concerns five different tumour marker assays examined in the context of 94 patients with advanced breast cancer treated in a prospectively randomised trial of different doses of medroxyprogesterone acetate (MPA). MPA was administered at doses of 500 or 1000 mg daily and clinical evaluation of patients was carried out according to UICC criteria. Carcinoembryonic antigen (CEA) was selected as a standard marker, with three assays for MUC1 mucins (epithelial mucin core antigens (EMCA), EMCA2 and BR-MA immunoradiometric assay) differing in antibody specificities for different mucin epitopes. An additional novel assay for soluble cytokeratin was also evaluated as an example of an independent marker with a different nature and biology. Sensitivity of individual assays ranged between 44 (EMCA2) and 69% (cytokeratin) and the use of two assays in combination led to sensitivities as high as 84% (cytokeratin+BR-MA). The proportion of patients found to be assessable by each assay ranged between 51 (EMCA2) and 76% (cytokeratin). Of those patients whose marker changes were assessable, those receiving the higher dose of MPA displayed significant falls in marker levels after 12 weeks of treatment. This effect was not observed in patients receiving 500 mg. The change in cytokeratin levels in patients undergoing high dose MPA therapy proved to be most marked. Using the cytokeratin assay, 91% (of 23 patients) of patients with progressive disease showed at least a 25% rise in serum marker levels. Of these, 66% showed increases before disease progression was detected clinically with a mean lead time of 14 weeks. There was very little difference between the responses of the five tumour marker assays in patients with stable or responding disease, the proportion of these patients with stable or falling tumour marker levels ranging between 58% (CEA) and 77% (EMCA). We conclude that the cytokeratin assay has an application in monitoring response to therapy and predicting tumour progression in advanced breast cancer patients with assessable tumour marker profiles, especially if used in combination with a MUC1 mucin assay.