By James C. Salwitz, MD
Breast cancer will kill more than 450,000 women worldwide this year, and in the United States alone, 232,000 will be newly diagnosed. Two important recent events shift the conversation from disease treatment to prevention. The most public was the stunning statement of actress Angelina Jolie that she had both her breasts removed because she carried a breast cancer gene (BRCA1). This announcement served to greatly increase awareness and discussion of choice in preventing the disease.
Second, was the decision by the U.S. Preventative Services Task Force (USPSTF) to recommend the use of medications for prevention of breast cancer in women who are at increased risk.
Many factors influence breast cancer risk
In order to prevent breast cancer, we must first understand its causes. While we do not know all, we do understand that certain factors increase the chance of getting breast cancer. Some of these risk factors can be reduced through improved lifestyle, but not all.
Most breast cancer occurs not because of known genetic mutations, but because of a combination of risk factors. One important risk factor is increasing age, with most breast cancers occurring in women 55 years of age and older.
Some risk factors include an early age for a first period (start of menses), a late first pregnancy, and no pregnancy at all. Breast-feeding decreases cancer rates. Prescription estrogen replacement, especially after menopause, increases breast cancer risk. The more alcohol a woman drinks, starting even with small amounts, the higher her chance of getting the disease. Obesity and low amounts of exercise increase the chance of developing breast cancer, too.
If a woman has increased breast density on mammogram, this increases the chance of being diagnosed with breast cancer. If a woman has any breast biopsies, particularly if the biopsies showed benign growth of the lining of milk ducts ("proliferation"), this increases risk. Certain benign duct changes, such as hyperplasia or atypia, greatly increase risk. Also, ductal or lobular carcinoma-in-situ (DCIS and LCIS) greatly increase the chance of developing invasive breast cancer.
Finally, family history, even without a defined cancer gene like BRCA1 or BRCA2, increases the likelihood a woman will get breast cancer. Each first-degree relative (mother, sister, daughter) who has breast cancer increases further the chance of breast cancer. The younger the breast cancer occurred, the greater the risk to the patient.
Tamoxifen and raloxifene appropriate for high-risk women
Thus, the USPSTF recognizes that even the healthiest lifestyle leaves many women at increased risk of getting breast cancer. Therefore, the agency studied alternatives that are available. Their conclusion was that certain women with increased risk should strongly consider taking the drugs tamoxifen or raloxifene for 5 years to try and prevent the disease. Both drugs are already FDA-approved for this use.
From the time a woman enters puberty, her body makes estrogen. Even if a woman has her ovaries removed or enters menopause, the fat cells in her body still make significant amounts of estrogen. Doctors believe that the more breast cells are exposed to estrogen, the more the chance of getting breast cancer. Tamoxifen and raloxifene block the strong estrogens made naturally by a woman's body.
Extensive research, which was reviewed in detail by the USPSTF, shows that tamoxifen and raloxifene when taken daily reduce breast cancer by 7 to 9 fewer cases per 1,000 women over 5 years.
If used widely, these drugs would prevent thousands of cases of breast cancer in the United States, and many more around the world. The USPSTF noted that the research has not yet shown the drugs prevent breast cancer deaths, but they believe that studies will eventually prove these drugs to be lifesavers. Tamoxifen probably gives more protection than raloxifene.
Benefits outweigh risks only for some women
When evaluating a medical treatment it is important to look at side effects. Drugs, which have complex effects on the human body, like tamoxifen and raloxifene have the potential to cause harm. Generally, side effects are more common with tamoxifen than raloxifene.
Like all estrogen related drugs, such as birth control pills, tamoxifen and raloxifene increase the chance of getting a blood clot in a vein or in the lung (embolism). Clots occur in about 1 woman out of a 1000 taking drugs like these, every year. Both drugs slightly increase the risk of strokes. Tamoxifen, but not raloxifene, increases the chance of endometrial cancer in post-menopausal women by 4 cases per 1,000 women every 5 years. Finally, both cause hot flashes and menopausal symptoms including loss of sex drive and occasional depression. On the other hand, both drugs prevent or improve osteoporosis.
In short, both drugs can decrease the risk of getting breast cancer, but also have the chance of side effects, with tamoxifen having slightly more benefit, but also slightly more side effects.
The USPSTF weighed who should and who should not take tamoxifen or raloxifene. They decided against the routine use of these drugs in women who are at average risk for getting breast cancer, because the risk of side effects outweighs the potential benefit for these women.
However, they made the strong recommendation that women with an estimated 5-year breast cancer risk of 3% or more, and low risk for side effects, should consider taking tamoxifen or raloxifene.
The women who might fit this "estimated 5-year risk of 3% or more" have (or have had):
-Older age (above 55)
-A family history of breast or ovarian cancer before the age of 50
-A personal history of atypical hyperplasia in a breast biopsy
-DCIS or LCIS
-Extremely dense breast tissue on mammograms
-Started their periods early and/or were pregnant late
-Certain benign (not cancerous) breast conditions
The USPSTF recommends that women who might meet these criteria talk with their doctor to review their specific medical histories in order to estimate their 5-year risk.
Women and their doctors must also look at general health to determine the likelihood of side effects from tamoxifen and raloxifene. For example, a woman who smokes is more likely to get blood clots and may not want to use tamoxifen.
The USPSTF recommendation adds another weapon in the arsenal against breast cancer. By making healthy lifestyle decisions a woman can reduce the chance she will be diagnosed with breast cancer. In addition, women who are still at high risk should have a conversation with their doctor about the possible the use of tamoxifen or raloxifene. It's a vital discussion that may save their lives.
Visit our page on medicines to reduce breast cancer risk to learn more.
Guest blogger James C. Salwitz, MD, is a medical oncologist who has been in private practice for 25 years, and a clinical professor at Robert Wood Johnson Medical School.