Hormone Therapy for Breast Cancer Treatment

Most cases of breast cancer are fueled by the hormones estrogen and progesterone. Hormone therapy, also called endocrine therapy, is used to remove or block hormones and stop or slow down the growth of cancer cells. If your cancer is hormone-sensitive, then hormone therapy may be part of your treatment plan.

If your doctor prescribes this for your early-stage breast cancer, plan on taking hormonal therapy for five years (and sometimes up to 10 years) after completing your primary treatments. The main benefit of this type of therapy is to prevent estrogen from fueling estrogen-responsive positive cancer cells, thus reducing your risk of recurrence. For breast cancer that is estrogen receptor-negative, hormonal therapy is not effective.

Anti-Estrogen Hormone Drugs

Hormones can be lowered by drugs and/or by surgery. Two classes of drugs are used for hormone therapy: selective estrogen receptor modulators (SERMs) such as tamoxifen and aromatase inhibitors (AIs). These are given based on your menopausal status and your breast cancer diagnosis.

A SERM or an aromatase inhibitor may be used with or without ovarian suppression therapy. Ovarian suppression therapy shuts down the ovaries (so they cannot produce estrogen) and may be accomplished surgically (by removing the ovaries), or medically (with injections of medication that will temporarily shut down the ovaries).

Tamoxifen works, simplistically, by binding to the estrogen receptors on breast cancer cells so that natural estrogen cannot bind (and allow the cells to grow and divide). Aromatase inhibitors, in contrast, block the enzyme (aromatase) that converts androgens produced by the adrenal glands into estrogen.

Below are commonly-used prescription drugs, plus information on how long they need to be taken.

Early-Stage Breast Cancer in Women

Menopausal
Status
Anti-Estrogen Drug Dosage Duration
Pre- Tamoxifen 5 years (and up to 10 years)
Pre- Combination of aromatase inhibitor and ovarian-suppression drugs  5 years (and up to 10 years)
Post- Aromatase inhibitor or tamoxifen 5 years (and up to 10 years)

The treatment of early stage breast cancer depends on menopausal status and characteristics of your tumor.

Premenopausal Women

For pre-menopausal women, tamoxifen is often given after primary treatment for breast cancer (surgery and possible chemotherapy and/or radiation). Since the primary source of estrogen before menopause is the ovaries, an aromatase inhibitor alone would be insufficient for reducing estrogen levels.

Because aromatase inhibitors may reduce the risk of recurrence somewhat more effectively than tamoxifen, they are sometimes recommended for premenopausal women who have a higher risk of recurrence. When this is done, the aromatase inhibitor must be combined with ovarian suppression therapy unless menopause (which sometimes occurs with chemotherapy) can be documented with a blood test. It's important to note that an absence of periods after chemotherapy does not necessarily mean a woman is truly menopausal.

Tamoxifen may also be combined with ovarian suppression therapy, and for those who are high risk, the combination may reduce recurrence (and improve survival) somewhat more than tamoxifen alone. This is particularly true for younger women who have larger or node positive tumors (see below).

Tamoxifen or an aromatase inhibitor plus ovarian suppression therapy is most often recommended for five years. For those who are high risk, extending hormone therapy for another five years (for a total of 10 years) may further reduce the risk of recurrence.

Menopausal Women

After menopause, the primary source of estrogen in the body is the peripheral conversion of androgens (produced in the adrenal gland) to estrogen, and therefore an aromatase inhibitor is often used after primary treatment. Tamoxifen is an alternative for those who are unable to use an aromatase inhibitor.

Treatment Duration

Hormonal therapy is most commonly recommended for five years to lower the risk of recurrence. In those who have a high risk of recurrence, however, extending hormonal therapy for another five years (for a total of 10 years) may be recommended. Treatment beyond five years reduces the risk of recurrence, but also increases the risk of side effects, and the choice must be weighed individually for each woman.

Relative Reduction in Recurrence Risk

When facing choices (such as whether to use tamoxifen or an aromatase inhibitor or whether to add in ovarian suppression therapy), it can be helpful to look at the relative effectiveness of these treatments.

In general, for smaller, node negative tumors, the risks of more aggressive therapy may outweigh the benefits. In contrast, for women who have a high risk of recurrence, more aggressive or combination therapy may justify a higher incidence of side effects.

Both tamoxifen and aromatase inhibitors reduce the risk of recurrence by roughly half. According to a 2020 study, combining tamoxifen with ovarian suppression therapy improved overall survival more than tamoxifen alone (but with increased side effects).

In premenopausal women, aromatase inhibitors appear to be slightly more effective than tamoxifen with an overall reduction in recurrence of around 30% and improved survival of 15% after fivew years.

In one study, the greatest reduction in recurrence among premenopausal women was in those who used a combination of an aromatase inhibitor and ovarian suppression therapy. It's important to note that, despite these apparent large differences, when survival rates are already very high, say with smaller and node negative tumors, the relative benefit may be small relative to the increase in side effects.

It's also important to briefly discuss the risk of late recurrence. For women who have estrogen receptor positive tumors, the risk of recurrence after five years is significant. In fact, for many women with these tumors, the cancer is more likely to recur after five years than in the first five years following treatments, and the risk of recurrence remains roughly the same every year for 20 years.

While chemotherapy lowers the risk of recurrence in the first five years, it has little effect in reducing late recurrences. Hormone therapy, by contrast, may reduce the risk of late recurrences, with a 2019 study showing that tamoxifen appears to reduce recurrence risk for at least 15 years after diagnosis.

Early-Stage Breast Cancer in Men

As for women, hormonal therapy is usually recommended after primary therapy (surgery with or without chemotherapy or radiation) for men with estrogen-receptor positive breast cancers. Since 99% of breast cancers in men are estrogen receptor positive, this includes the majority of men with the disease.

According to 2020 guidelines by the American Society of Clinical Oncology, tamoxifen is the preferred treatment. An aromatase inhibitor plus ovarian suppression therapy may be used for men who are unable to take tamoxifen.

It's recommended that tamoxifen be continued for five years to lower the risk of recurrence. Men who have tumors that have a high risk of recurrence may continue hormonal therapy another five years for a total of 10 years.

Men who have had breast cancer should not take testosterone or androgen supplements.

Metastatic Disease

Hormonal therapy for metastatic breast cancer depends on menopausal status (in women) and may include tamoxifen or an aromatase inhibitor (with or without ovarian suppression therapy) or Faslodex (fulvestrant) which can be used sequentially.

If recurrence or progression occurs during the course of one category of hormonal therapy, a different category is often used. For example, if recurrence occurs while taking tamoxifen, an aromatase inhibitor (with ovarian suppression therapy for premenopausal women) may be suggested.

Unlike early stage breast cancer, in which the goal of treatment is a cure, with metastatic disease the goal is usually to control the disease while minimizing side effects. Therefore, your doctor will carefully discuss options while keeping in mind your quality of life during treatment.

Menopausal
Status
Anti-Estrogen Drug Dosage Duration
Any Tamoxifen Until no longer effective (or side effects are unacceptable)
Any Intermediate and high-dose estrogens Until no longer effective (or side effects are unacceptable)
Any Aromatase inhibitors Until no longer effective (or side effects are unacceptable)
Post- Toremifene Until no longer effective (or side effects are unacceptable)
Post- Faslodex injection Until no longer effective (or side effects are unacceptable)
Any Megace Until no longer effective (or side effects are unacceptable)
Any Androgens (male hormones) Until no longer effective (or side effects are unacceptable)
Pre- Combination of ovarian-suppression drugs (SERMs and AIs) Until no longer effective (or side effects are unacceptable)

Drug Side Effects

There are both common and less frequent but serious side effects that may occur with hormone therapy.

Common Side Effects

Having your ovaries shut down or removed or taking hormone therapy can bring on medical menopause. You may not get all of the symptoms of natural menopause, but here are some common side effects you may experience from this type of therapy:

  • Hot flashes
  • Night sweats
  • Mood swings
  • Vaginal dryness
  • Fatigue

Muscle and joint pains (arthralgia) are also quite common, especially with aromatase inhibitors.

Serious Side Effects

Serious side effects may also occur with hormonal therapy, and differ between tamoxifen and aromatase inhibitors.

Tamoxifen has anti-estrogen effects on some tissues and pro-estrogen effects in others. Infrequent side effects with tamoxifen may include blood clots (deep venous thrombosis with the potential of pulmonary emboli) as well as increased risk of uterine cancer.

Aromatase Inhibitors can lead to a decrease in bone density resulting in osteopenia or osteoporosis. Combining a bisphosphonate (medications traditionally used for used for osteoporosis) with aromatase inhibitors for some postmenopausal women may reduce this concern for some women.

A Word From Verywell

Knowing the hormone receptor status of your breast cancer is a critical factor when determining the appropriate treatment. Fortunately, there are effective hormonal treatments for both early-stage cancer as well as metastatic disease.

Since there are so many options now, it's very important to work actively with your oncologist to determine what is right for you as an individual with your specific tumor.

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