Estrogen Receptors (ERs) and Cancer

Estrogen and the ERs are implicated in breast cancer, ovarian cancer, colon cancer, prostate cancer and endometrial cancer - Advanced colon cancer is associated with a loss of ER-β, the predominant ER in colon tissue, and colon cancer is treated with ER-β-specific agonists.

Harris HA, Albert LM, Leathurby Y, Malamas MS, Mewshaw RE, Miller CP, Kharode YP, Marzolf J, Komm BS, Winneker RC, Frail DE, Henderson RA, Zhu Y, Keith JC (2003). "Evaluation of an estrogen receptor-beta agonist in animal models of human disease". Endocrinology 144 (10): 4241-9.

A test result of ER-positive (ER+) - means that ERs are “over-expressed” and that estrogen is causing a tumor to grow. ER+ tumors are slightly slower-growing than ER- tumors, and the cancer should respond well to hormone suppression treatments.

▪ 0 is no receptors found,

▪ 1+ is a small number,

▪ 2+ is a medium number, and

▪ 3+ is a large number of receptors.

ERs and Breast Cancer.     Test results show ER+ in ~ 70% of breast cancer cases

(1) Estrogen binding to ER stimulates proliferation of mammary cells  (increases cell division/DNA replication) leading to mutations.

(2) Estrogen metabolism may produce genotoxic waste.

-   ER-α is associated with more differentiated tumors.    ER-β involvement is controversial.

-   Different versions of the ESR1 gene associated with different risks of developing breast cancer.

Deroo BJ, Korach KS (2006). "Estrogen receptors and human disease". J. Clin. Invest. 116(3): 561-7.

-   Mainstream endocrine therapy.    Anti-estrogen therapy works by blocking the hormone receptors, preventing them from signaling the cancer cells to grow.

•  Some commonly used ER antagonists in breast tissue:

Selective estrogen receptor modulators (SERMS):

▪Tamoxifen - antagonist at breast /agonist at bone and uterus

▪Raloxifene (Evista) - antagonist at breast and uterus / agonist at bone

Selective estrogen receptor down-regulator (SERD):

▪Faslodex (chemical name: fulvestrant) - antagonistic in all tissues

•  Some common aromatase inhibitor drugs (prevent conversion of androgens to estrogen) - only useful for postmenopausal women, because postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme, while premenopausal women get most of their estrogen directly from their ovaries.

▪Femora (chemical name: letrozole)

▪Aromasin (chemical name: exemestane)

▪Arimidex (chemical name: anastrozole)

▪PROGESTERONE is a natural aromatase inhibitor

References

Leslie Baumann. Cosmetic Dermatology: Principles and Practice, Second EditionMcGraw Hill Professional,Apr 8, 2009