If you or a loved one has increased risk factors for breast cancer, developing a risk reduction plan is an important conversation to have with your doctor. At our hospital, we always recommend tackling obesity and alcohol usage first, but for those at high risk, chemoprevention can be a small piece of the risk reduction puzzle.
Cancer chemoprevention is the use of drugs, either manufactured or natural, to delay or prevent the diagnosis of cancer. Breast cancer prevention drugs like tamoxifenA drug that blocks estrogen from affecting organs, such as the breast., raloxifene and aromatase inhibitorsDrugs that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands. An example is anastrozole (Arimidex). (AIs) are the most commonly used drugs for preventative therapy.
Who Are the Best Candidates For Breast Cancer Prevention Drugs?
Chemoprevention does not treat malignantCancerous. breast cancer if you’ve already been diagnosed. But you might be a good candidate for breast cancer prevention drugs if you have a benignNot harmful; not cancerous (referring to a cell or mass). (i.e. non-cancerous) disease that puts you in the high-risk category. This includes high-risk breast lesionsA general term indicating a change in body tissue, often used as a synonym for tumors., lobular carcinoma in situ (LCIS), atypical lobular hyperplasiaExcessive cell growth. (ALH) or atypical ductal hyperplasia (ADH).
Preventative therapy might also be a good fit for you if your Gail Model risk score is above 1.7. The Gail Model is a tool used by doctors to determine your breast cancer risk level and looks at factors such as your age, family history and reproductive history.
Tamoxifen & Raloxifene
To grow, breast cancer requires the natural hormoneA chemical substance produced in the body that controls and regulates the activity of certain cells or organs. estrogen. EstrogenA female sex hormone that is primarily produced by the ovaries. Its primary function is to regulate the menstrual cycle and assist in the production of secondary sex characteristics such as breasts. It may even play a role in the production of cancer cells in the breast tissue. is the principle female sex hormone, but it is also found in lower doses in men, one of the reasons why men can get breast cancer, too. Both tamoxifen and raloxifene work as an anti-estrogen pill binding with the estrogen receptors in breast cancer cells instead of natural estrogen in the body. By reducing estrogen available to cancer cells, growth is inhibited. Because of this, tamoxifen and raloxifene are part of the class of medications called selective estrogen receptor modulators (SERMs).
Because of the way SERMs work, binding to estrogen receptors, they are effective against the 80% of breast cancers that are estrogen-responsive, called ER-positive breast cancer. ER-negative cancers like triple negative breast cancer are not typically treated with tamoxifen or raloxifene.
While similar, the two medications diverge slightly in both their history and usage. Up until the late 90s, tamoxifen had been primarily prescribed to treat early stage breast cancer and to prevent recurrenceThe reappearance of the disease after it has been treated. In breast cancer, recurrence following primary breast cancer can be local (in the same place), regional (in surrounding tissue) or metastatic (in some other part of the body). of cancer after surgeries. In 1992, the Breast Cancer Prevention Trial studied the drug’s role as a breast cancer preventative and found a substantial risk reduction. The accompanying study, published in the Journal of the National Cancer Institute in 1998 reported:
“The decreased risk occurred in women aged 49 years or younger (44%), 50–59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50%.”
In 1999, tamoxifen became the first medication approved by the U.S. Food and Drug Administration (FDA) for breast cancer prevention.
Raloxifene, introduced in 1997, was originally used to prevent postmenopausal osteoporosis. Like Tamoxifen, doctors took note of its breast cancer preventative properties and in 2007, the FDA approved its use as a breast cancer prevention drug as well. According to a 1999 study published in JAMA,
“Raloxifene reduced the risk of newly diagnosed invasive breast cancer by 76% during a median of 40 months of treating postmenopausal women for osteoporosis. This was attributable to a 90% reduction in the risk of estrogen receptor–positive breast cancer.”
Because raloxifene is FDA-approved for postmenopausal women only, Tamoxifen is the sole choice for younger women looking for preventative therapy. Luckily the vast majority of patients looking for preventative therapy have already reached menopauseThe end of a woman’s menstrual cycles, defined as 12 consecutive months of no menstrual periods. so they can choose between raloxifene, tamoxifen or an aromatase inhibitor (AI).
Aromatase Inhibitors
Aromatase inhibitors (AIs) are another class of drug, slightly different from SERMs. Instead of blocking estrogen directly, AIs work by blocking the enzymeA substance produced by a living organism which causes a specific biochemical reaction. aromatase, hence the name “aromatase inhibitor.” In the body, aromatase helps convert other hormones into estrogen, so by blocking aromatase, production of estrogen is reduced. Because the aromatase enzyme does not play a role in the estrogen production in the ovaries—which produce the majority of the body’s estrogen in premenopausal women—AIs work best for women who have already reached menopause. Unlike SERMs, they turn off the production of small amounts of estrogen from fat cells and adrenal glands that still continues after menopause. And like SERMs, AIs are most effective treating hormone-responsive breast cancers.
Currently, AIs—which include the drugs anastrozole, exemestane, and letrozole—are only FDA-approved for breast cancer treatment, not prevention, but there have been a number of promising studies. Exemestane and anastrozole, however, are included in the standard guidelines used by oncologists as options and are increasingly being used in practice based on the excellent results from these studies that show efficacy as a preventative therapy.
While the future of chemoprevention is very bright, it’s important to remember that risk reduction starts with lifestyle changes like better nutrition, exercise, and the avoidance of smoking and moderation of alcohol usage. Breast self-exams and regular screenings like mammograms, and clinical breast exams are an integral and important part of catching breast cancer early when it’s in more treatable stages.
While breast cancer prevention drugs like tamoxifen, raloxifene and aromatase inhibitors do not make our risk levels zero, they do offer an extra level of protection and can be a great component of an integrated risk reduction program.