Human
breast neoplasms can be divided into
hormone-dependent and
hormone-independent subtypes.
Estrogen is the major hormonal stimulus for growth of the dependent
tumors. Failure to respond to
estrogen suppression
therapy could reflect either an incomplete lowering of
estrogens or the hormonal independence of the
tumor. To address this issue, we compared the levels of several
estrogens and other
hormones in women experiencing objective responses (the responders) and
disease progression (the progression group) during
therapy with the
aromatase-steroidogenesis inhibitor,
aminoglutethimide, and replacement
hydrocortisone. Pretreatment hormonal profiles of the
estrogens, and
androgens,
ketosteroids,
thyroxine,
polypeptide hormones, and
carcinoembryonic antigen did not differ significantly among response groups. During treatment, the levels of all
estrogens were suppressed to a similar degree in the progression group and in the responders. Urinary
estrone, for example, fell to 16.7 +/- 3.2% of basal in the responders versus 16.3 +/- 3.8% of basal in the progression group. These data suggested that lack of
estrogen suppression did not explain the response to treatment in the patients receiving
aminoglutethimide-
hydrocortisone. This finding differs from our results in a similarly analyzed control group of patients treated with surgical
adrenalectomy. Levels of the weak
androgens,
dehydroepiandrosterone sulfate and
androstenedione, were found to be higher in the progression group compared to the responders. This observation could not be explained by differences in
duration of treatment between groups. Analysis at 1 to 12 weeks, 13 to 24 weeks, and 25 to 36 weeks after initiating treatment indicated higher
androgen levels at each time point in the progression group. In addition, the results were not attributable to differing serum levels of
aminoglutethimide among responder groups. While the finding of higher
androgen levels in the responder group remains unexplained, this study indicates that incomplete
estrogen suppression is not responsible for lack of
tumor response in patients with progressive disease during amino-
glutethimide-
hydrocortisone therapy.