Progestins in Breast Cancer Treatment: A Reveiw

Abstract

The two most widely used synthetic progestins in breast cancer treatment, medroxyprogesterone acetate (MPA) and megestrol acetate (MA), are reviewed with regard to pharmacological, endocrinological and clinical aspects. In high oral doses as second- or first-line endocrine therapy in advanced breast cancer, they give a similar response rate as tamoxifen (TAM) and aminoglutethimide (AG). The mechanism of action is probably complex. Considerable changes in serum levels of different hormones are induced by progestin treatment. The decrease of serum estrone sulfate (E1S) may be part of the therapeutic mechanism. Some studies suggest that the two drugs, MPA and MA, have a different mode of action, and possibly a low cross resistance. Randomized studies using the two progestins with a cross-over design may answer these questions. Further studies on the influence of progestin on different receptors and growth factors are warranted. To determine the most effective clinical dose of the two progestins, studies with increasing therapeutic doses are needed.

Endocrine Therapy for Advanced/Metastatic Breast Cancer

“…64,65 Progestins have similar RRs to tamoxifen. 66,67 They represent a useful option in some patients, but are associated with significant weight gain, fluid retention, vaginal bleeding, and risk of thromboembolic events. 65,68 The AIs anastrozole and exemestane were shown to be marginally superior to MA in terms of survival in initial trials, as shown in Table 1.…”

Evaluation of plasma and tissue estrogen suppression with third-generation aromatase inhibitors: Of relevance to clinical understanding?

“…Megestrol acetate was about as effective as aminoglethimide for breast cancer treatment [70]. While the mechanism by which megestrol acetate executed its anti-tumour effects are incompletely understood [71], due to suppression of adrenal steroid synthesis treatment with megestrol acetate suppressed plasma estrogen levels to about the same degree as aminoglutethimide [72] This, however, did not induce cross-resistance between megestrol acetate and aromatase inhibitors [71,73].…”

Cross-resistance to different aromatase inhibitors in breast cancer treatment.

“…Recently, a randomised study revealed treatment with letrozole 2.5 mg daily to be superior to aminoglutethimide 500 mg daily (Gershanovich et al 1998). While the full mechanism of the anti-tumour action of progestins administered in high doses to breast cancer patients is not understood (Lundgren 1992), it is now clear that megestrol acetate 160 mg daily suppresses plasma oestrogen levels by 75-80% in postmenopausal women (Lundgren et al 1996). Recent studies have shown that letrozole given as 2.5 mg daily produces a better response rate compared with megestrol acetate (Dombernowsky et al 1998).…”