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Progestins and breast cancer.

Jorge R Pasqualini1

  • 1Hormones and Cancer Research Unit, Institut de Puériculture et de Périnatalogie, Paris, France. Jorge.Pasqualini@wanadoo.fr

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
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PubMed
Summary

Progestins impact various tissues and biological systems. Some progestins can inhibit estradiol bioformation in breast cancer cells, but their overall effect on breast cancer remains controversial and requires further clinical investigation.

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Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Progestins bind to progesterone receptors and can interact with other steroid receptors, influencing numerous physiological processes.
  • Breast cancer tissue locally synthesizes estradiol (E2) via aromatase and sulfatase pathways, crucial for tumor growth.
  • The role of progestins in breast cancer is complex and debated, with conflicting evidence regarding incidence and mortality.

Purpose of the Study:

  • To investigate the mechanisms by which progestins affect estradiol bioformation in breast cancer cells.
  • To explore the controversial effects of progestins on breast cancer incidence and outcomes.
  • To highlight the need for further clinical trials to clarify progestin therapy in breast cancer and hormone-related conditions.

Main Methods:

  • Review of existing evidence on progestin interactions with steroid receptors and their systemic effects.
  • Analysis of pathways involved in local estradiol biosynthesis in breast cancer.
  • Examination of studies on progestin and tibolone metabolites' effects on key enzymes (sulfatase, 17beta-hydroxysteroid dehydrogenase) and sulfotransferase activity in breast cancer cells.

Main Results:

  • Certain progestins and tibolone metabolites inhibit enzymes essential for estradiol production in breast cancer cells.
  • These compounds can also enhance the activity of sulfotransferases, leading to estrogen inactivation.
  • Evidence regarding progestin's impact on breast cancer incidence is contradictory, with studies showing increases, no change, or decreases.

Conclusions:

  • Progestins exhibit multifaceted biological activities beyond the endometrium, affecting tissues like the breast, liver, bone, and brain.
  • Specific progestins demonstrate potential to modulate local estradiol synthesis in breast cancer, but their clinical impact is unclear.
  • Further well-designed clinical trials are necessary to elucidate the precise role of progestins in breast cancer treatment and hormone replacement therapy.