How Tamoxifen Prevents Breast Cancer Recurrence

Benefits and Side Effects of Tamoxifen in Premenopausal 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. What is the benefit of using this drug after primary treatment for breast cancer, what are the common side effects, and what are the risks?

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).

There are three primary used for tamoxifen:

  • Women and men diagnosed with estrogen receptor-positive, early-stage breast cancer after surgery, chemotherapy 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.

Tamoxifen is usually not considered beneficial for those who have estrogen or progesterone negative breast cancer.

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 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 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 with high and low 70-gene 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 estrogen cannot, essentially starving the cancer cells.

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 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). We aren't 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 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. 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.

Warnings

Drug Interactions

Due to the way in which it is metabolized, tamoxifen may interact with both 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.

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 2 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. 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.

The Bottom Line

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.

Sources:

National Cancer Institute. Breast Cancer Treatment (PDQ)—Health Professional Version

Sahebkar, A., Serban, M., Penson, P. et al. The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis. Drugs. 2017. 77(11):1187-1197.

Yu, Z., Guo, X., Jiang, Y. et al. Adjuvant Endocrine Monotherapy for Postmenopausal Early Breast Cancer Patients with Hormone-Receptor Positive: A Systemic Review and Network Meta-Analysis. Breast Cancer. 2017 Jul 28.

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