Tamoxifen

by National Cancer Institute

1. What is tamoxifen?

Tamoxifen (Nolvadex®) is a medication in pill form that interferes with the activity of estrogen (a hormone). Tamoxifen has been used for more than 20 years to treat patients with advanced breast cancer. It is used as adjuvant, or additional, therapy following primary treatment for early stage breast cancer. In women at high risk of developing breast cancer, tamoxifen reduces the chance of developing the disease. Tamoxifen continues to be studied for the prevention of breast cancer. It is also being studied in the treatment of several other types of cancer. It is important to note that tamoxifen is also used to treat men with breast cancer.

2. How does tamoxifen work on breast cancer?

Estrogen promotes the growth of breast cancer cells. Tamoxifen works against the effects of estrogen on these cells. It is often called an "anti-estrogen." As a treatment for breast cancer, the drug slows or stops the growth of cancer cells that are present in the body. As adjuvant therapy, tamoxifen helps prevent the original breast cancer from returning and also helps prevent the development of new cancers in the other breast.

3. Are there other beneficial effects of tamoxifen?

While tamoxifen acts against the effects of estrogen in breast tissue, it acts like estrogen in other tissue. This means that women who take tamoxifen may derive many of the beneficial effects of menopausal estrogen replacement therapy, such as lower blood cholesterol and slower bone loss (osteoporosis).

4. Can tamoxifen prevent breast cancer?

Research has shown that when tamoxifen is used as adjuvant therapy for early stage breast cancer, it reduces the risk of recurrence of the original cancer and also reduces the risk of developing new cancers in the other breast. Based on these findings, the National Cancer Institute (NCI) funded a large research study to determine the usefulness of tamoxifen in preventing breast cancer in women who have an increased risk of developing the disease. This study, known as the Breast Cancer Prevention Trial (BCPT), was conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a component of the NCI's Clinical Trials Cooperative Group Program. This study found a 49 percent reduction in diagnoses of invasive breast cancer among women who took tamoxifen. Women who took tamoxifen also had 50 percent fewer diagnoses of noninvasive breast tumors, such as ductal or lobular carcinoma in situ. However, there are risks associated with tamoxifen. Some are even life threatening. The decision to take tamoxifen is an individual one: The woman and her doctor must carefully consider the benefits and risks of therapy.

Women with an increased risk of developing breast cancer have the option to consider taking tamoxifen to reduce their chance of developing this disease. They may also consider participating in the Study of Tamoxifen and Raloxifene (see question 5).

At this time, there is no evidence that tamoxifen is beneficial for women who do not have an increased risk of developing breast cancer.

5. What is the Study of Tamoxifen and Raloxifene (STAR), and how can a woman learn more about it?

The Study of Tamoxifen and Raloxifene (STAR) is a clinical trial (a research study conducted with people) designed to see whether the osteoporosis drug raloxifene (Evista®) is more or less effective than tamoxifen in reducing the chance of developing breast cancer in women who are at an increased risk of developing the disease. Raloxifene may have breast cancer risk reduction properties similar to those found in tamoxifen. This study will also examine whether raloxifene has benefits over tamoxifen, such as fewer side effects.

The STAR trial, which began in June 1999, is being conducted by the NSABP. It will involve about 22,000 postmenopausal women who are at least 35 years old and are at increased risk for developing breast cancer.

Women can learn more about the STAR trial in several ways. They can call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The number for deaf and hard of hearing callers with TTY equipment is 1-800-332-8615. Information is also available on NSABP's Web site at http://www.nsabp.pitt.edu or on the Study of Tamoxifen and Raloxifene (STAR) Trial Digest Page on the NCI's Web site at http://www.cancer.gov/star on the Internet.

6. What are some of the more common side effects of taking tamoxifen?

In general, the side effects of tamoxifen are similar to some of the symptoms of menopause. The most common side effects are hot flashes and vaginal discharge. Some women experience irregular menstrual periods, headaches, fatigue, nausea and/or vomiting, vaginal dryness or itching, irritation of the skin around the vagina, and skin rash. As is the case with menopause, not all women who take tamoxifen have these symptoms. Men who take tamoxifen may experience headaches, nausea and/or vomiting, skin rash, impotence, or a decrease in sexual interest.

7. Does tamoxifen cause cancers of the uterus?

Tamoxifen increases the risk of two types of cancer that can develop in the uterus: endometrial cancer, which arises in the lining of the uterus, and uterine sarcoma, which arises in the muscular wall of the uterus. Like all cancers, endometrial cancer and uterine sarcoma are potentially life-threatening. Women who have had a hysterectomy (surgery to remove the uterus) and are taking tamoxifen are not at increased risk for these cancers.

Endometrial cancer

In the BCPT, women who took tamoxifen had more than twice the chance of developing endometrial cancer compared with women who took a placebo (an inactive substance that looks the same as, and is administered in the same way as, tamoxifen). The risk of endometrial cancer in women taking tamoxifen was in the same range as (or less than) the risk in postmenopausal women taking single-agent estrogen replacement therapy. This risk is about 2 cases of endometrial cancer per 1000 women taking tamoxifen each year.

Most of the endometrial cancers that have occurred in women taking tamoxifen have been found in the early stages, and treatment has usually been effective. However, for some breast cancer patients who developed endometrial cancer while taking tamoxifen, the disease was life threatening.

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