Treatment of advanced or metastatic breast cancer: Several types of hormone therapy are approved to treat metastatic or recurrent hormone-sensitive breast cancer. Hormone therapy is also a treatment option for ER-positive breast cancer that has come back in the breast, chest wall, or nearby lymph nodes after treatment (also called a locoregional recurrence).

Two SERMs are approved to treat metastatic breast cancer, tamoxifen and toremifene. The antiestrogenfulvestrant is approved for postmenopausal women with metastatic ER-positive breast cancer that has spread after treatment with other antiestrogens.7 It may also be used in premenopausal women who have hadovarian ablation.

The aromatase inhibitors anastrozole and letrozole are approved to be given to postmenopausal women as initial therapy for metastatic or locally advanced hormone-sensitive breast cancer.8,9 These two drugs, as well as the aromatase inhibitor exemestane, are used to treat postmenopausal women with advanced breast cancer whose disease has worsened after treatment with tamoxifen.10

Some women with advanced breast cancer are treated with a combination of hormone therapy and a targeted therapy. For example, the targeted therapy drug lapatinib (Tykerb®) is approved to be used in combination with letrozole to treat hormone receptor–positive, HER2-positive metastatic breast cancer in postmenopausal women for whom hormone therapy is indicated.

Another targeted therapy, palbociclib (Ibrance®), has been granted accelerated approval for use in combination with letrozole as initial therapy for the treatment of hormone receptor–positive, HER2-negativeadvanced breast cancer in postmenopausal women. Palbociclib inhibits two cyclin-dependent kinases (CDK4 and CDK6) that appear to promote the growth of hormone receptor–positive breast cancer cells.

Palbociclib is also approved to be used in combination with fulvestrant for the treatment of women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer whose cancer has gotten worse after treatment with another hormone therapy.

Neoadjuvant treatment of breast cancer: The use of hormone therapy to treat breast cancer before surgery (neoadjuvant therapy) has been studied in clinical trials.11 The goal of neoadjuvant therapy is to reduce the size of a breast tumor to allow breast-conserving surgery. Data from randomized controlled trials have shown that neoadjuvant hormone therapy—in particular, with aromatase inhibitors—can be effective in reducing the size of breast tumors in postmenopausal women. The results in premenopausal women are less clear because only a few small trials involving relatively few premenopausal women have been conducted thus far.

No hormone therapy has yet been approved by the FDA for the neoadjuvant treatment of breast cancer.

Can hormone therapy be used to prevent breast cancer?

Yes. Most breast cancers are ER positive, and clinical trials have tested whether hormone therapy can be used to prevent breast cancer in women who are at increased risk of developing the disease.

A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial found that tamoxifen, taken for 5 years, reduced the risk of developing invasive breast cancer by about 50% in postmenopausal women who were at increased risk.12 Long-term follow-up of another randomized trial, the International Breast Cancer Intervention Study I, found that 5 years of tamoxifen treatment reduces the incidence of breast cancer for at least 20 years.13 A subsequent large randomized trial, the Study of Tamoxifen and Raloxifene, which was also sponsored by NCI, found that 5 years of raloxifene (a SERM) reduces breast cancer risk in such women by about 38%.14

As a result of these trials, both tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for this use regardless of menopausal status. Raloxifene is approved for use only in postmenopausal women.

Two aromatase inhibitors—exemestane and anastrazole—have also been found to reduce the risk of breast cancer in postmenopausal women at increased risk of the disease. After 3 years of follow-up in a randomized trial, women who took exemestane were 65% less likely than those who took a placebo to develop breast cancer.15 After 7 years of follow-up in another randomized trial, women who took anastrozole were 50% less likely than those who took placebo to develop breast cancer.16 Both exemestane and anastrozole are approved by the FDA for treatment of women with ER-positive breast cancer. Although both are also used for breast cancer prevention, neither is approved for that indication specifically.

What are the side effects of hormone therapy?

The side effects of hormone therapy depend largely on the specific drug or the type of treatment.5 The benefits and harms of taking hormone therapy should be carefully weighed for each woman. A common switching strategy used for adjuvant therapy, in which patients take tamoxifen for 2 or 3 years, followed by an aromatase inhibitor for 2 or 3 years, may yield the best balance of benefits and harms of these two types of hormone therapy.17

Hot flashes, night sweats, and vaginal dryness are common side effects of hormone therapy. Hormone therapy also disrupts the menstrual cycle in premenopausal women.

Less common but serious side effects of hormone therapy drugs are listed below.

Tamoxifen

  • Risk of blood clots, especially in the lungs and legs12
  • Stroke17
  • Cataracts18
  • Endometrial and uterine cancers17,19
  • Bone loss in premenopausal women
  • Mood swings, depression, and loss of libido
  • In men: headaches, nausea, vomiting, skin rash, impotence, and decreased sexual interest

Raloxifene

  • Risk of blood clots, especially in the lungs and legs12
  • Stroke in certain subgroups17

Ovarian suppression

  • Bone loss
  • Mood swings, depression, and loss of libido

Aromatase inhibitors

  • Risk of heart attack, angina, heart failure, and hypercholesterolemia20
  • Bone loss
  • Joint pain21–24
  • Mood swings and depression

Fulvestrant

  • Gastrointestinal symptoms25
  • Loss of strength24
  • Pain