Hormonal Therapy and Breast Cancer

Hormonal (really anti-hormonal) therapies for breast cancer change the balance of estrogen in the body. The effect of these treatments is to block hormones that can stimulate growth of breast cancer cells in breast cancers with hormone receptors. Hormonal therapies can prevent cancer from coming back (recurrence) in early breast cancer or control disease in advanced breast cancer.

When a breast cancer is removed or a biopsy is done, one of the tests in the laboratory determines whether or not there are estrogen and/or progesterone receptors on your breast cancer cells. These receptors are like “docking stations” that the hormones estrogen and progesterone can connect to and stimulate the growth of breast cancer. When the receptors are present, the breast cancer is estrogen receptor positive (ER+) and /or progesterone receptor positive (PR+). If the breast cancer cells have estrogen and/or progesterone receptors, this predicts that the hormonal therapies will be a useful part of your treatment. If your breast cancer cells have few or no estrogen or progesterone receptors (ER-negative, PR-negative) it is unlikely that the anti-estrogen therapies will benefit you.

If either of the hormone receptors is positive (ER+ or PR+), then the hormone therapies are used as a treatment for early stage breast cancer. Large clinical trials have shown that hormone therapies can prevent recurrence and death from breast cancer. Hormone therapies can also be used to treat a recurrence in the breast and lymph nodes or to treat advanced or metastatic breast cancer (outside the breast in other organs, eg bone).

If you are pre-menopausal (still having periods, menstruating) most of your estrogen is made in your ovaries. If you are post-menopausal (no menstrual periods for a year, often confirmed by blood tests) you still produce small amounts of estrogen in your body - just not in the ovary. The adrenal glands (near your kidneys) produce a hormone, androstenedione (a weak male hormone) that is then changed into estrogen by an enzyme called aromatase. The aromatase enzyme is found in many cells including fat and muscle. Therefore, whether you are pre or post menopausal will effect your treatment options for hormone therapy. Blocking estrogen stimulation of hormone receptor positive breast cancer is the goal in both pre- and post-menopausal women, but the treatment strategies may be different.

The use of anti-hormone medications in early stage breast cancer is called adjuvant therapy (treatment given after surgery or surgery and radiation to decrease the risk of cancer recurrence). It may be the only systemic (system-wide) treatment or it may also be given following chemotherapy. The recommendations that you will hear from your physician(s) take many factors into consideration including: your overall health, your menopausal status, estrogen and progesterone receptors, another receptor called HER2/neu, the stage (how far along the cancer is), the grade (a measure of tumor biology and behavior) and other tests that are done to predict risk. Hormone therapy is usually given for 5 years; some studies are looking at longer term treatment in higher risk cancers.

Once you know that your breast cancer is ER positive and/or PR positive, the issues that you and your physician(s) will consider include:

1. What is the risk of my breast cancer coming back (recurrence) if I do local therapy (surgery, radiation) alone?
2. How much can hormonal therapy lower my risk of the cancer coming back? (recurrence can be in the breast or in other organs)
3. What is /are the best hormone therapy medications for me?
4. What are the risks and side effects of those medicines?
5. Does the benefit outweigh the risk?

The recommendations and your preferences can then lead to a treatment decision.

- Block the action of estrogen by blocking the receptors on the breast cancer cells:

SERMS (selective estrogen receptor modulators) block the receptors (loading docks) so that the growth signals to the cells are interrupted. Tamoxifen (Nolvadex®) is a SERM and is the standard of care for pre-menopausal women. Tamoxifen works in a setting where estrogen is still being produced by the ovaries as well as in post-menopausal women. Tamoxifen reduces the risk of recurrence and death from hormone receptor positive breast cancer; studies have shown that 5 years of treatment still reduces risk at 15 years after diagnosis.

Tamoxifen is a complex medication that has anti-estrogen effects on some tissues and estrogen-like effects on other tissues. The anti-estrogen effects lead to the primary benefit of reducing breast cancer recurrence risk and the menopausal side effects like hot flashes and vaginal dryness. The estrogen-like effects lead to , an added benefit of maintaining bone strength and side effects of an increased risk of blood clots and a small increased risk of developing uterine cancer. Please see the tamoxifen (Nolvadex®) drug sheet more more information.

In some settings, pre-menopausal women may receive injections of goserelin (Zoladex®), leuprolide (Lupron®), or triptorelin (Decapeptyl®) which are drugs that stop hormones from the pituitary gland in the brain from stimulating the production of estrogen in the ovaries. This treatment, called ovarian suppression, is usually done along with treatment with tamoxifen. Clinical trials are evaluating treatment with ovarian suppression combined with aromatase inhibitors for pre-menopausal women. Ovaries can be surgically removed or radiated to block estrogen, but this is not often done (except for preventative surgery in cases where the risk of ovarian cancer is high).

- Lower the level of hormones in the body that can stimulate breast cancer cell growth. Estrogen stimulates breast cancer growth. If the amount of estrogen is decreased, breast cancer growth is decreased.

Aromatase inhibitors lower the amount of estrogen made outside the ovaries.

Aromatase inhibitors only work in post-menopausal women because they do not block estrogen from the ovaries. Examples of aromatase inhibitors include: anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®). These drugs can be given instead of tamoxifen or after 2 or 3 years of tamoxifen as adjuvant hormone therapy for early stage breast cancer.All are pills taken by mouth on a daily basis (tamoxifen can be taken once or twice per day).

Please see individual drug sheets for specific information for each drug

Decision Making

This area of breast cancer care is evolving and will change over time. Clinical trials are ongoing to determine which hormonal therapy is best in different situations. The American Society of Clinical Oncology (an organization of cancer physicians) updates the state of the knowledge as it changes. Changes can be made if one medicine is producing side effects or as the medical knowledge changes.

Clinical trials

There may be clinical trials available to you and appropriate to your medical story. Your doctor(s) will discuss clinical trials for which you are eligible.Please also visit the clinical trials section of our website.

Hormonal Treatment of Advanced or Metastatic Breast Cancer

Hormonal therapy can be effective in controlling advanced breast cancer in women who have ER+ and /or PR+ disease. The breast cancer will sometimes be retested (by biopsy or surgery) for receptor status because it may change from that of the original breast cancer (usually going from positive to negative), or the original test might have been incorrect.

Treatment choices are similar to those reviewed above for early stage breast cancer, and include tamoxifen (Nolvadex®) or a similar drug called toremifene (Fareston®) and the aromatase inhibitors - anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®).

Again menopausal status affects the choice of therapy. For pre-menopausal women, ovarian suppression is usually used along with either tamoxifen or aromatase inhibitors. In post-menopausal women, the aromatase inhibitors (AI’s) have been shown to be more effective than tamoxifen and are a very good treatment strategy. Tamoxifen may still be effective and is often used after the aromatase inhibitors stop working.

Treatment for advanced breast cancer includes a series of medications used to control the cancer. Typically one medication is given until the cancer is no longer responding, then a switch is made to another effective medication. Additional options for hormone therapy are described below.

There is another drug that is only used to treat advanced breast cancer at this time. Fulvestrant (Faslodex®) is a ‘pure’ estrogen receptor blocker, that works like tamoxifen, to block the receptors in the breast cancer cells. Unlike the other hormonal therapies described above which are oral medicines, fulvestrant is an injection given into the muscle once per month. Fulvestrant can be used either before or after aromatase inhibitor therapy.

Megestrol acetate (Megace®, medroxyprogesterone), acts in a similar way to the hormone progesterone, and is also an effective treatment for advanced breast cancer. Megace is given either as a pill or a liquid and also can also improve appetite in people with poor appetites due to cancer.

Other hormonal therapies are under study, including the use of high dose estrogens. Estrogen can cause blood clots, so this medication must be used with caution and is usually given after the above medications are no longer working to control the cancer.

Please see individual drug sheets for specific information for each drug

Clinical Trials

You may be eligible for treatment on a clinical trial using hormone therapy.

There are ongoing clinical trials that will continue to provide information that will help you and your physician(s) tailor your treatment decisions. New hormonal agents are being studied, new trials will open and this area of therapy, for women with estrogen and or progesterone positive breast cancer, will expand.

Resources to find these trials include the UCSF Cancer Center's Clinical Trial website or the NCI sponsored trial matching program breastcancertrials.org now online in the Bay Area.

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