How Tamoxifen Prevents Breast Cancer Recurrence

Benefits and Side Effects of Tamoxifen in Premenopausal Breast Cancer

tamoxifen pills on nightstand used for breast cancer
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Tamoxifen, also known by the brand name Nolvadex, is one of the more commonly prescribed medications to prevent breast cancer recurrence, and when used appropriately, may reduce the risk of recurrence (of breast cancer coming back) by roughly 50 percent. The drug may also be used to reduce the chance that a woman will develop breast cancer in the first place, or to slow the growth of metastatic breast cancer. Tamoxifen works by binding to estrogen receptors on breast cells so that estrogen can't bind and stimulate growth. Learn about the potential side effects, how drug interactions may occur, and how tamoxifen differs from aromatase inhibitors.

Overview

Tamoxifen is a medication which has both anti-estrogen and estrogen-like effects, depending on the particular type of tissue in the body where it acts. It is classified as a selective estrogen receptor modulator (SERM) along with the medication Evista (raloxifene).

Indications

There are three primary uses for tamoxifen:

  • Women and men diagnosed with estrogen receptor-positive, early-stage breast cancer after surgery, chemotherapy, and/or radiation to reduce the risk of recurrence.
  • Women and men diagnosed with advanced stage or metastatic breast cancer which is hormone receptor-positive.
  • Primary breast cancer prevention for those at an increased risk of developing the disease. People who are living with or "surviving" having a susceptibility (genetic predisposition) to breast cancer are now being referred to as "cancer previvors".

Tamoxifen is usually not considered beneficial for those who have estrogen or progesterone negative breast cancer. For those who have estrogen receptor as well as HER2 positive cancer, your doctor may recommend tamoxifen (or an aromatase inhibitor), a HER2 targeted medication such as Herceptin, or both depending on your specific situation.

Tamoxifen comes in both 10 mg or 20 mg tablets with the most common dose being 20 mg once daily. There are several important drug interactions which can greatly reduce the effectiveness of the drug. It is usually taken daily for 5 to 10 years or until a person switches over to an aromatase inhibitor.

Benefits

Tamoxifen was approved in 1998 and has since been found effective in treating breast cancer for millions of people. It is still considered an excellent option if you are premenopausal or are postmenopausal and cannot take an aromatase inhibitor.

When used after primary treatment (eg. surgery) it may reduce your risk of breast cancer recurrence by half if your tumor was estrogen receptor positive. It can also reduce your risk of developing another cancer in the same breast or a new cancer in your other breast by up to 50 percent. This reduced risk holds true both for those who have a high or low risk.

It may be helpful to realize that tamoxifen continues to have benefits in reducing the risk of recurrence even after you stop taking the drug.

In addition to its effects on reducing breast cancer risk or recurrence, tamoxifen has other benefits as well. In contrast to its anti-estrogen effects on breast tissue, tamoxifen has estrogen-like effects on bone. Therefore tamoxifen (as well as Evista) may help slow or stop bone loss. (In contrast, aromatase inhibitors often lead to bone loss). Tamoxifen may also lower cholesterol levels, specifically LDL cholesterol.

How It Works

Breast cancer cells which are estrogen receptor positive are essentially fed by estrogen. Estrogen in the body binds to proteins on the surface of these cells (estrogen receptors) to signal the cell to divide and grow. Tamoxifen binds to this receptor so that estrogen cannot, essentially starving the cancer cells.

In premenopausal women the majority of estrogen in the body is produced by the ovaries. After menopause, the conversion of androgens (produced in the adrenal glands) to estrogen in the primary source of estrogen. Aromatase inhibitors work by blocking this conversion, and hence, reducing estrogen levels. Since aromatase inhibitors do not address estrogen produced by the ovary, they are ineffective before menopause unless a person has received ovarian suppression therapy.

Side Effects and Risks

Many of the common side effects of tamoxifen are essentially the side effects of having a reduced amount of estrogen in the body (menopause). Therefore hot flashes, night sweats, vaginal dryness, discharge, and drainage, and reduced libido are common. As a quick note, if these bother you, hot flashes are linked with better survival from breast cancer. Cataracts may also occur.

Tamoxifen's actions on uterine (endometrial) tissue can raise the risk of uterine cancer. This risk is dependent on the length of time you are on the drug. This risk is highest for women over the age of 50 but is less than one percent.

Tamoxifen can increase your risk of developing blood clots either in your legs (deep vein thrombosis) or lungs (pulmonary embolism). It's not certain at this time, but tamoxifen may also increase the risk of heart attack or stroke.

When to Call Your Doctor

It's important to call your doctor if you have any symptoms you are concerned about, but in particular, you should call if you develop any of the following:

  • Abnormal vaginal bleeding
  • Pain in your pelvis
  • Leg pain and/or swelling
  • Chest pain
  • Shortness of breath
  • Weakness, numbness or tingling
  • Vision issues

Tamoxifen vs. Aromatase Inhibitors

Tamoxifen and aromatase inhibitors differ when it comes to both the benefits and risks.

For women who are postmenopausal or those who are premenopausal and have received ovarian suppression therapy, an aromatase inhibitor may offer greater benefits in reducing the risk of recurrence

This is one reason why oncologists may recommend switching to an aromatase inhibitor if you reach menopause, or treating you with ovarian suppression therapy to induce menopause.

Aromatase inhibitors also cause menopausal symptoms but can accelerator bone loss rather than reduce it like tamoxifen. Bone and joint pain can occur with either class of drugs but is much more common with aromatase inhibitors. With respect to cost, tamoxifen therapy is usually much less expensive than any of the aromatase inhibitors.

Drugs classified as aromatase inhibitors include Aromasin (exemestane), Arimidex (anastrozole), and Femara (letrozole).

Warnings and Interactions

As with many medications, there are situations in which tamoxifen should not be used or where caution is needed.

Drug Interactions

Due to the way in which it is metabolized, tamoxifen may interact with both some common prescription and over-the-counter medications. Talk to your doctor about any other medications you use and make sure your pharmacist is aware as well. In particular, several antidepressants, as well as over-the-counter allergy medications, may reduce the effectiveness of tamoxifen. Before the interaction was understood, it was found that the survival rate among women using tamoxifen was significantly lower among women using one antidepressant.

Pregnancy

Due to a relatively high rate of birth defects, tamoxifen should not be used in pregnancy, and the drug should be stopped at least two months before trying to get pregnant.

How Long You Should Take It

Based on clear evidence from two large randomized phase III clinical studies (ATLAS and aTTom), a 10 year rather than a five-year adjuvant treatment with Tamoxifen is associated with a smaller risk of recurrence and a reduction in breast cancer mortality.

This reduction in breast cancer recurrence must be weighed against potential side effects for each person as an individual. For example, if your cancer has a relatively high risk of recurrence (such as if lymph nodes are positive), the benefit of longer treatment may clearly outweigh risk. In contrast, if your tumor has a very low risk of recurrence, the potential adverse effects of tamoxifen (such as blood clots) may outweigh the potential benefit.

If you are premenopausal, your doctor may recommend tamoxifen for 3 to 5 years before switching over to an aromatase inhibitor for 5 more years.

It's important to stick with your medication. Unfortunately, many people either miss doses or discontinue these medications prematurely, resulting in an elevated risk of recurrence.

A Word From Verywell

Tamoxifen can significantly reduce the risk of recurrence of breast cancer after primary treatment with surgery, chemotherapy and/or radiation therapy. Like any medication, tamoxifen has risks and side effects and the benefits of treatment must be weighed against these risks. Be sure to discuss your symptoms with your doctor and talk with her if you experience any side effects. Keep the lines of communication open to ensure tamoxifen works for you without significant drawbacks.

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