Hormone therapy in breast cancer

Diagrammatic representation for the Hypothalamic/Pituitary-Gonadal Axis and therapy used to interrupt this circuit.

Rational:
Some cancer cells originating from these organs express receptors to female hormones. Thus, the female hormones estrogen and progesterone can stimulate the growth of some types of breast cancer cells. These types are known as hormone responsive. Thus, hormone therapy can be used to block this effect.

Types:
There are two main types of hormone therapy for breast cancer.
1. Drugs that block estrogen and progesterone growth stimulating effect:
• Selective estrogen receptor modulators (SERMs).
• Aromatase inhibitors.
• Estrogen receptor antagonists.

2. Drugs or surgery to stop the production of female hormones from the ovaries:
• Pituitary down regulators

1. Drugs that block estrogen and progesterone growth stimulating effect:
• Selective estrogen receptor modulators (SERMs): Tamoxifen
Tamoxifen (Nolvadex) blocks estrogen receptors in breast cells; as such, it blocks the estrogen-stimulated tumor growth effect. Tamoxifen is the most common hormone therapy used in breast cancer for 25 years.

• Aromatase inhibitors
After menopause women, produce estrogen from their precursors outside the gonadal system (ovaries) at peripheral tissues like fat, liver, and muscle. Aromatase is the enzyme responsible for the conversion of estrogen precursors into estrogen in these tissues. Aromatase inhibitors are relatively new drugs in the treatment of hormone responsive breast cancer in postmenopausal women or premenopausal women after effective ovarian castration.

Aromatase inhibitors are further divided into:
- Irreversible suicide inhibitors: e.g. Exemestane (Aromasin)
They cause complete destruction of the enzymes; consequently, the enzyme is irreversibly inactivated.

- Reversible competitive inhibitors: e.g. Anastrozole (Arimidex®) and Letrozole (Femara)

They bind reversibly to the active site of the enzyme and compete with the active substrate. Consequently, the inhibition they produce is reversible and lasts as long as they occupy the enzyme active site.


2. Drugs used to stop the production of female hormones from the ovaries:

• Pituitary down regulators:e.g. Leuprolide or Zoladex
LH and FSH are hormones released from the pituitary to regulate the function of the gonads (ovaries in females and tests in males). Medical castration with LHRH analogues is used to treat premenopausal women with hormone sensitive breast cancer. The term medical castration refers to decrease in circulating LH and FSH in addition to down-regulation of gonadal receptors for LH and FSH. In such way a complete inhibition of gonadal (ovarian) function and a decline in sex hormones occur; estrogen and progesterone.