What types of hormone therapy are used for breast cancer?
Several strategies are used to treat hormone-sensitive breast cancer:
Blocking ovarian function: Because the ovaries are the main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.
Ovarian ablation can be done surgically in an operation to remove the ovaries (called oophorectomy) or by treatment with radiation. This type of ovarian ablation is usually permanent.
Alternatively, ovarian function can be suppressed temporarily by treatment with drugs called gonadotropin-releasing hormone (GnRH) agonists, which are also known as luteinizing hormone-releasing hormone (LH-RH) agonists. These medicines interfere with signals from the pituitary gland that stimulate the ovaries to produce estrogen.
Examples of ovarian suppression drugs that have been approved by the U.S. Food and Drug Administration (FDA) are goserelin (Zoladex®) and leuprolide (Lupron®).
Blocking estrogen production: Drugs called aromatase inhibitors are used to block the activity of an enzyme called aromatase, which the body uses to make estrogen in the ovaries and in other tissues. Aromatase inhibitors are used primarily in postmenopausal women because the ovaries in premenopausal women produce too much aromatase for the inhibitors to block effectively. However, these drugs can be used in premenopausal women if they are given together with a drug that suppresses ovarian function.
Examples of aromatase inhibitors approved by the FDA are anastrozole (Arimidex®) and letrozole (Femara®), both of which temporarily inactivate aromatase, and exemestane (Aromasin®), which permanently inactivates aromatase.
Blocking estrogen’s effects: Several types of drugs interfere with estrogen’s ability to stimulate the growth of breast cancer cells:
• Selective estrogen receptor modulators (SERMs) bind to estrogen receptors, preventing estrogen from binding. Examples of SERMs approved by the FDA for treatment of breast cancer are tamoxifen(Nolvadex®) and toremifene (Fareston®). Tamoxifen has been used for more than 30 years to treat HR+hormone receptor–positive breast cancer.
Because SERMs bind to estrogen receptors, they can potentially not only block estrogen activity (i.e., serve as estrogen antagonists) but also mimic estrogen effects (i.e., serve as estrogen agonists). SERMs can behave as estrogen antagonists in some tissues and as estrogen agonists in other tissues. For example, tamoxifen blocks the effects of estrogen in breast tissue but acts like estrogen in the uterus and bone.
• Other antiestrogen drugs, such as fulvestrant (Faslodex), work in a somewhat different way to block estrogen’s effects. Like SERMs, fulvestrant binds to the estrogen receptor and functions as an estrogen antagonist. However, unlike SERMs, fulvestrant has no estrogen agonist effects. It is a pure antiestrogen. In addition, when fulvestrant binds to the estrogen receptor, the receptor is targeted for destruction.
How is hormone therapy used to treat breast cancer?
There are three main ways that hormone therapy is used to treat hormone-sensitive breast cancer:
Adjuvant therapy for early-stage breast cancer: Research has shown that women who receive at least 5 years of adjuvant therapy with tamoxifen after having surgery for early-stage ER-positive breast cancer have reduced risks of breast cancer recurrence, including a new breast cancer in the other breast, and death at 15 years.2
Tamoxifen is approved by the FDA for adjuvant hormone treatment of premenopausal and postmenopausal women (and men) with ER-positive early-stage breast cancer, and the aromatase inhibitor anastrozole andletrozole are approved for this use in postmenopausal women.
A third aromatase inhibitor, exemestane, is approved for adjuvant treatment of early-stage breast cancer in postmenopausal women who have received tamoxifen previously.
Until recently, most women who received adjuvant hormone therapy to reduce the chance of a breast cancer recurrence took tamoxifen every day for 5 years. However, with the introduction of newer hormone therapies, some of which have been compared with tamoxifen in clinical trials, additional approaches to hormone therapy have become common.3–5 For example, some women may take an aromatase inhibitor every day for 5 years, instead of tamoxifen. Other women may receive additional treatment with an aromatase inhibitor after 5 years of tamoxifen. Finally, some women may switch to an aromatase inhibitor after 2 or 3 years of tamoxifen, for a total of 5 or more years of hormone therapy. Research has shown that for postmenopausal women who have been treated for early-stage breast cancer, adjuvant therapy with an aromatase inhibitor reduces the risk of recurrence and improves overall survival, compared with adjuvant tamoxifen.6
Decisions about the type and duration of adjuvant hormone therapy must be made on an individual basis. This complicated decision-making process is best carried out by talking with an oncologist, a doctor who specializes in cancer treatment.