Hormonal Therapy for Early-Stage Hormone Receptor-Positive Breast Cancer

February 16, 2016

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) provides recommendations on the use of hormonal therapy for early-stage breast cancer. This guide for patients is based on the most recent recommendations.

Understanding hormonal therapy

Hormonal therapy, also called endocrine therapy, for hormone receptor-positive breast cancer is an adjuvant therapy. Adjuvant therapy is treatment given after surgery, chemotherapy, and/or radiation therapy to lower the chance of the cancer coming back.

Hormone receptor-positive breast cancer is the most common type of breast cancer. This kind of cancer depends on hormones called estrogen and/or progesterone to grow. The goal of adjuvant hormonal therapy is to lower the levels of these hormones in the body or to block the hormones from getting to any remaining cancer cells. If the hormones cannot get to the cancer cells, the cancer cannot use them to grow.

The hormonal therapy options for hormone receptor-positive breast cancer depend on whether a woman has been through menopause before diagnosis. Menopause usually begins in a woman’s mid-40s or early to mid-50s when her ovaries stop releasing eggs and her body makes less estrogen and progesterone. Women who have not been through menopause are considered premenopausal. Woman who have been through menopause are considered postmenopausal. It is important to note that some women may still be premenopausal even if they stop menstruating.

Hormonal therapy for hormone receptor-positive breast cancer includes the following options:

  • Aromatase inhibitors (AIs) reduce the amount of estrogen in a woman's body by stopping tissues and organs other than the ovaries from making estrogen. AIs are not used for women who are premenopausal because of the way AIs work. In women who are premenopausal, the ovaries are still producing estrogen. AIs stimulate estrogen production in the ovaries of women who have not been through menopause. Therefore, it is important that women have gone through menopause before using AIs. AIs include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). All work the same way even though they are three different brands, and research suggests that they are equally effective and have similar side effects.

  • Tamoxifen blocks a cell’s ability to use estrogen, which stops or slows the growth of cells that depend on it. Tamoxifen is effective both for women who are premenopausal and for those who are postmenopausal.

  • Ovarian suppression refers to the use of drugs or surgery to stop the ovaries from producing estrogen. It may be used in addition to another type of hormonal therapy for women who have not been through menopause. There are 2 methods used for ovarian suppression:

    • Drugs called gonadotropin or luteinizing releasing hormone (GnRH or LHRH) analogs that stop the ovaries from making estrogen, causing temporary menopause. Goserelin (Zoladex) and leuprolide (Lupron) are GnRH agonists given by injection that stop the ovaries from making estrogen for 1 to 3 months.

    • Surgery to remove the ovaries, which also stops estrogen production. However, this is permanent.

Recommendations for women who are premenopausal

Women who have hormone receptor-positive breast cancer who are premenopausal before diagnosis or are going through menopause when they are diagnosed have the following options:

  • Tamoxifen for 5 years. Then, treatment is based on whether or not they have been through menopause in those 5 years.

    • If a woman has not been through menopause after the first 5 years of treatment, she can continue tamoxifen for another 5 years, for a total of 10 years of tamoxifen.

    • If a woman has been through menopause after the first 5 years of treatment, she can continue tamoxifen for an additional 5 years or switch to an AI for 5 more years. This would be a total of 10 years of hormonal therapy. Only women who are clearly postmenopausal should consider taking an AI.

  • Ovarian suppression for 5 years along with additional hormonal therapy, such as tamoxifen, may be recommended in the following situations, depending on a woman’s age and risk of recurrence:

    • For women who have a high risk of cancer recurrence.

    • For women with stage II or stage III cancer when chemotherapy is also recommended.

    • For women with stage I or stage II cancer with a higher risk of recurrence who may consider also having chemotherapy.

  • Ovarian suppression is not recommended in addition to another type of hormonal therapy in the following situations:

    • For women with cancer that is not likely to recur.

    • For women with stage I cancer when chemotherapy is not recommended.

    • For women with a tumor less than 1 cm in size that has not spread to the lymph nodes.

Recommendations for women who are postmenopausal

Women with hormone receptor-positive breast cancer who are postmenopausal before diagnosis have the hormonal therapy options listed below. All of these options have been tested in clinical trials and are considered good options for women who have been through menopause. Talk with your doctor about how each of these may affect your quality of life to find the option that is best for you.

  • Tamoxifen for 10 years

  • An AI for 5 years

  • Tamoxifen for 5 years, followed by an AI for up to 5 years. This would be a total of 10 years of hormonal therapy.

  • Tamoxifen for 2 to 3 years, followed by up to 5 years of an AI for a total of 7 to 8 years of hormonal therapy.

What This Means for Patients

Women with breast cancer should discuss options for hormonal treatment with their doctor. This conversation should cover the risks and benefits of different treatment options, including the risk that the cancer will return with or without hormonal therapy, the likely side effects, how long treatment will last, and the costs of treatment. Each woman's specific medical circumstances should be carefully considered when discussing treatment options. Because AIs work only in women who have been through menopause, it is important that a woman is actually postmenopausal before evaluating hormonal therapy options.

At this time, it is not known which treatment option is better at reducing the risk of the cancer returning. AIs and tamoxifen have slightly different side effects, although they are often similar in severity. The side effects of AIs include joint pain and stiffness, vaginal dryness, increased cholesterol, heart disease, and weakening bones. The side effects of tamoxifen include hot flashes, vaginal discharge or dryness, leg cramps, and, rarely, blood clots and a slightly increased risk of uterine cancer. Women who experience too many or too severe side effects from one of the hormonal therapy options should talk with their doctors about changing to a different hormonal treatment.

Questions to Ask the Doctor

For women who are considering adjuvant hormonal therapy:

  • Is my breast cancer hormone receptor-positive or hormone receptor-negative? What does this mean?

  • Why may I need hormonal therapy?

  • How many years of hormonal therapy do I need?

  • Are there any reasons to believe I might not benefit from hormonal therapy?

  • What are the benefits and risks of AIs?

  • What are the benefits and risks of tamoxifen?

  • How do the side effects of AIs compare with tamoxifen?

  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?

For women who were premenopausal when diagnosed:

  • What is my menopausal status now, and how does this affect my options for treatment?

  • Do you recommend ovarian suppression? Why?

For women who have completed 2 to 3 years of either tamoxifen or AI therapy:

  • Is there a reason I should switch to a different hormonal therapy?

  • How many more years of hormonal therapy do I need if I continue to take my current hormonal therapy? If I switch to a different hormonal therapy?

  • How will the side effects change if I switch to a different hormonal therapy?

For women who have completed 5 years of either tamoxifen or AI therapy:

  • Do you recommend further hormonal therapy? If so, with what drug and how long would I continue treatment?

  • If I start a different drug, what are the possible side effects?

Helpful Links

Read the entire clinical practice guideline at www.asco.org/guidelines/endocrinebreast

Guide to Breast Cancer

Estrogen and Progesterone Receptor Testing for Breast Cancer

Follow-Up Care for Breast Cancer