Breast Cancer

Targeted Therapy According to ER/PR

Testing for estrogen receptors (ER) and progesterone receptors (PR) is important to determine appropriate treatment options for breast cancer. Because the growth of tumors that produce an excess of ER and/or PR is driven by estrogen, these tumors are more likely to respond to targeted treatment with drugs that lower the amount of estrogen in the body or block its action. Treatment with antiestrogen drugs is known as hormone (endocrine) therapy.

Treatment of ER+/PR+ breast cancer

Hormone therapy may be used for breast cancer of any stage, if testing shows an excess of ER and/or PR. For early-stage ER+/PR+ breast cancer, hormone therapy is given after surgery and may be given in sequence with chemotherapy, depending on a woman’s individual risk of recurrence. For metastatic ER+/PR+ breast cancer, hormone therapy may be given as primary treatment, and often, multiple hormone therapy agents are used before (or after) resorting to chemotherapy.

Hormone therapy drugs are classified as selective estrogen-receptor modulators (SERMs), aromatase inhibitors (AIs), and selective estrogen receptor downregulators (SERDs). These drugs work in different ways and each have different side effects (Table 1). The primary difference among these drugs is whether they can be used for women who are premenopausal or postmenopausal. You and your doctor will consider several additional factors when choosing the best type of hormone therapy.

Table 1. Types of hormone therapy for breast cancer

  Menopause status Action Notes
SERMs*
  tamoxifen 
    (Nolvadex)
 
  toremifene
    (Fareston)
 
Premenopausal and postmenopausal
 
Postmenopausal women with advanced ER+/PR+ cancers or cancers with unknown ER/PR status
 
Temporarily block estrogen receptors on breast cancer cells, preventing estrogen from binding to them
 
Has been traditional adjuvant hormone therapy for more than 30 years
Aromatase inhibitors (AIs)
  anastrozole
    (Arimidex)
  exemestane
    (Aromasin)
  letrozole
    (Femara)
Postmenopausal Prevents the body from making estrogen by blocking the enzyme aromatase Associated with fewer serious side effects than tamoxifen
Estrogen receptor downregulator
  fulvestrant
    (Faslodex)
Postmenopausal Eliminates estrogen receptors on the tumor Approved only for advanced breast cancers that have stopped responding to tamoxifen or toremifene
Luteinizing hormone-releasing Hormone analogs
  goserelin
    (Zoladex)
Premenopausal Eliminates ovarian production of estrogens Indicated for use in the palliative treatment of advanced breast cancer in premenopausal and perimenopausal women
Progestin
  megastrol acetate
    (Megace)
Premenopausal and postmenopausal Modifies the action of other hormones in the body and also has a cytotoxic effect on tumor cells Indicated for the palliative treatment of advanced breast cancer

*SERMs = selective estrogen-receptor modulators

SERMs

Tamoxifen (Nolvadex) has been used for several decades as part of adjuvant breast cancer treatment. Studies have shown that taking tamoxifen for five years after surgery for early-stage breast cancer reduces the chances of recurrence by more than 40 percent. Tamoxifen is also used as part of treatment for metastatic breast cancer. Both premenopausal and postmenopausal women can take tamoxifen. Another SERM, toremifene (Fareston), is used only for postmenopausal women with an advanced ER+/PR+ breast cancer. Raloxifene (Evista) is not indicated for the treatment of breast cancer.

Tamoxifen and toremifene do cause side effects, primarily symptoms similar to menopause: hot flashes, irritability, fluctuations in emotions, etc. Serious side effects, although rare, can occur, including an increased risk of uterine cancer or deep vein thrombosis (blood clots in the leg). For most women, however, the benefits outweigh the risks.

AIs

A newer class of hormone therapy drugs, AIs block the production of estrogen. Because of the way they work, AIs are recommended only for women who were postmenopausal at the time therapy is being considered. Several clinical trials have indicated that AIs offer a significant survival benefit compared with tamoxifen and also shown that AIs substantially reduce the risk of recurrence, whether used as the initial hormone treatment, as sequential treatment (used after a period of treatment with tamoxifen), or as extended treatment (used after the traditional five years of treatment with tamoxifen).

On the basis of these studies, both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend that postmenopausal women with ER+/PR+ breast cancer consider an AI treatment approach. The NCCN recommends the use of tamoxifen alone only for women who do not wish to take an AI or women for whom an AI is not appropriate.

Several clinical trials are being done in an effort to answer many questions that still remain about AIs, such as whether one AI is more effective than another, what the long-term side effects are, and what the optimum length of treatment should be.

Other hormone therapies

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

Removal or inactivation of the ovaries (by surgery or radiation therapy) is another type of hormone therapy. Used for more than 100 years, the procedure substantially reduces the production of estrogens in premenopausal women.

Luteinizing hormone-releasing hormone (LHRH) analogs are drugs that block the mechanism that causes the ovaries to make estrogen. These drugs provide an equivalent alternative to surgical removal of the ovaries in premenopausal women.

Progestins (megestrol acetate [Megace]) probably reduce the production of estrogens by indirect suppression of estrogen-producing tissues and are effective in the management of ER+ metastatic breast cancer. They are only used in the treatment of advanced breast cancer.

High-dose estrogens and synthetic androgens (similar to male hormones) are also successful in managing metastatic breast cancer, although they have been largely replaced by SERMs, AIs and SERDs in clinical practice.

Treatment of ER-/PR- breast cancer

Hormone therapy is not effective for breast cancers that do not express ER/PR. Chemotherapy alone is used for these tumors or in combination with HER2-directed treatments if the tumor is HER2+.

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