Overview of Hormonal Therapy for Breast Cancer

Hormonal therapies work against breast cancer tumors that are hormonal receptor positive (ER positive) by limiting the supply of estrogen or progesterone that is available to help the cancer cells grow. The more strongly receptor positive the tumor is, the greater the effectiveness of hormonal therapies.

What are Estrogen and Progesterone?

Estrogen, a hormone produced primarily by the ovaries, promotes growth and maintenance of the female reproductive system, including breasts. Progesterone is a similar hormone. These hormones stimulate the growth of both normal and abnormal breast cells, including some cancerous cells, by interacting with specific regions, known as receptors, on the surface of cancer cells.

What does "ER positive" mean?

About two out of every three breast cancers have estrogen receptors and are called estrogen receptor positive or ER positive. Nearly half of all breast cancers have progesterone receptors. These tumors are called progesterone receptor positive or PR positive. Together they are referred to as hormone receptor-positive or hormone receptor-negative tumors.

How do hormonal therapies work?

Hormonal therapies reduce the impact of estrogen in the body in 1 of 3 ways.

• They occupy the cell surface receptors so that estrogen cannot get to the cancer cells.

• They reduce the level of estrogen in the body by preventing it from being converted from other hormones, or

• They shut down estrogen production by the ovaries.

Selective Estrogen Receptor Modulators (SERMs)

A class of drugs called selective estrogen receptor modulators or SERMs blocks estrogen's ability to stimulate cell growth by occupying the cell surface receptors so that estrogen cannot get to the cancer cells. SERMs block the actions of estrogen in breast tissues by occupying the estrogen receptors on the cells. With a SERM drug in the estrogen receptor, there is no place for the real estrogen to stimulate growth of the cell. Unlike real estrogen, the SERM drugs do NOT send messages to the breast cell nucleus to grow and divide, and yet they DO send estrogen-like signals when they go to the estrogen receptors in bone cells, liver cells and other cells in the body.

What are some commonly used hormonal therapies?

The most commonly used hormonal therapy is the selective estrogen receptor modulator, or SERM, called tamoxifen.

Another drug, called raloxifene, brand name Evista®, has been shown to be as effective as tamoxifen for reducing the risk of breast cancer in postmenopausal women. The drug is not yet recommended as a treatment option.

What are aromatase inhibitors?

Aromatase inhibitors work by preventing an enzyme called aromatase found in the adrenal glands, ovaries, body fat and muscles from converting 2 hormones, testosterone and androstenedione, to estrogen. Thus, it interferes with the body's ability to make estrogen. By limiting the amount of estrogen in the body, tumor growth may be delayed or limited in tumors that are hormone-receptor positive.

Two aromatase inhibitors have been approved for treatment in postmenopausal women: Arimidex® and Femara®.

Shutting Down Estrogen Production

The third way to reduce the impact of estrogen is to stop the ovaries from making estrogen and progesterone in the body. This is done in one of two ways: by surgically removing the ovaries, called an oophorectomy, or by shutting them down with a drug called an LHRH agonist. LHRH stands for luteinizing hormone-releasing hormone. Luteinizing hormone, which is produced by the pituitary gland, stimulates production of hormones that promote estrogen production by the ovaries. An LHRH agonist such as Zoladex® blocks LHRH so LH and follicle stimulating hormone are not produced by the pituitary gland. When these hormones are not produced estrogen production by the ovaries shuts down.

Hormone Therapy and Menopause

For younger women, Zoladex® may produce a reversible menopause. When the drug is stopped, the ovaries may begin to function again. Surgical removal of the ovaries produces permanent menopause.