Hormone Therapy for Breast Cancer

Whether you receive adjuvant hormone therapy depends on the hormone status of your tumor. Hormone therapy is effective only for tumors that are ER-positive and/or PR-positive. It is important to note that hormone therapy for breast cancer differs from hormone replacement therapy used to reduce the symptoms of menopause. The hormone therapy drugs used for breast cancer treatment are used to reduce the amount of estrogen, which drives the growth of ER-positive/PR-positive tumors. These drugs, known as antiestrogen agents, lower the amount of estrogen in the body or block its action.

The types of hormone therapy drugs are classified as selective estrogen-receptor modulators (SERMs), aromatase inhibitors (AIs), and estrogen receptor downregulators. Hormone therapy drugs differ with respect to how they work, who they can be used for, and what side effects they can cause (Table 1). SERMs and AIs are taken as a once daily pill; an estrogen receptor downregulator is given as a once-monthly injection.

Tamoxifen is a SERM that has been used for over two decades as part of adjuvant breast cancer treatment. Studies have shown that the use of tamoxifen for 5 years after surgery for early-stage breast cancer reduces the chances of cancer recurrence by nearly 40%. The drug can also be used as part of treatment for metastatic breast cancer. Tamoxifen can be used by both premenopausal and postmenopausal women. Another SERM, toremifene (Fareston) is used only for postmenopausal women who have an advanced ER-positive/PR-positive breast cancer or a cancer with an unknown hormone receptor status.

Fulvestrant is an estrogen receptor downregulator, which means that it eliminates estrogen receptors on the tumor cells, rather than just blocking them. The drug is approved only for postmenopausal women who have advanced breast cancer that no longer responds to tamoxifen or toremifene.

Tamoxifen and toremifene are associated with side effects, primarily hot flushes, night sweats and other symptoms usually associated with menopause or estrogen deficit. Serious side effects, although rare, can occur; the drugs may increase the risk of uterine cancer or deep vein thrombosis (blood clots in the leg). For most women, however, the benefit of tamoxifen or toremifene outweighs the risks.

AIs represent a newer class of hormone therapy drugs. Because of the way they work, AIs are recommended only for women who were postmenopausal at the time of the breast cancer diagnosis. The results of some clinical trials have indicated that AIs are better than tamoxifen for lowering the risk of recurrence. AIs have been shown to substantially reduce the risk of recurrence when used as the initial hormone treatment, when used after a period of treatment with tamoxifen (sequential treatment), or when used after the traditional 5 years of treatment with tamoxifen (extended treatment). In addition, AIs are associated with fewer serious side effects than tamoxifen. The most common side effects of AIs are joint stiffness and pain, and the risk for osteoporosis and heart problems may be increased.

There are still many questions surrounding the choice of tamoxifen or an AI for postmenopausal women. Although an AI is better than tamoxifen at reducing the risk of recurrence, it has not been shown to lengthen overall survival. The three available AIs have not been directly compared with each other, so it is not clear if one is more effective than the others. Because AIs have not been in use for as long as tamoxifen, much less is known about their long-term side effects. Also, the optimum length of treatment with an AI has not been clearly defined. Lastly, it is not known whether all women derive greater benefit with the initial use of an AI, compared with sequential or extended use of an AI. The cost of hormone treatment may also be a factor; tamoxifen is less expensive than an AI.

Two studies have demonstrated a survival benefit with the use of tamoxifen followed by an AI, which led the NCCN to recommend that tamoxifen alone be used only for women who do not wish to take an AI or for whom an AI is contraindicated. Several clinical trials are being done in an effort to answer continuing questions about the choice of tamoxifen or an AI and the optimum course of hormone therapy.

Another form of hormone therapy currently being evaluated in clinical trials is the use of drugs to block the mechanism that causes the ovaries to make estrogen. These drugs, called luteinizing hormone-releasing hormone (LHRH) analogs, are an alternative to surgical removal of the ovaries in women who are premenopausal. Goserelin (Zoladex) and leuprolide (Lupron) are two LHRH analogs that are being studied as adjuvant therapy in conjunction with tamoxifen or an AI in premenopausal women.

Table 1. Types of Hormone Therapy for Breast Cancer
 

• American Cancer Society: www.cancer.org, Detailed Guide to Breast Cancer; Breast Cancer Profiler Tool(decision-making tool)
• ASCO's patient Web site: www.cancer.net, Breast Cancer Treatment
• Breastcancer.org: www.breastcancer.org, Treatment and Side Effects
• Susan G. Komen for the Cure: www.komen.org, Understanding Cancer: Treatment

• Breast cancer treatment with Femara (letrozole) and Tamoxifen