The treatment of breast cancer is changing following FDA-approval of a new class of drugs called anti-aromatase agents.
Estrogen is a female hormone produced by the ovaries and adrenal glands and is found circulating in the blood. Breast cancer cells have estrogen receptors and when exposed to estrogen, are stimulated to grow. Increased exposure to estrogen increases the growth of cancer cells. The basis of hormonal therapy as a treatment for breast cancer is to block or prevent the cancer cells from being exposed to estrogen.
Currently, the most common hormonal treatment for ER-positive breast cancer is an anti-estrogen called tamoxifen. Tamoxifen blocks estrogen receptors and prevents the estrogen-stimulated growth of breast cancer cells. Although tamoxifen remains the most commonly used hormonal treatment for breast cancer, now, a new class of hormonal agents called anti-aromatase agents has emerged for the treatment of ER-positive breast cancer.
Aromatase is an enzyme (protein) that is involved in the process through which hormones in the body are converted to estrogen. Anti-aromatase agents work by inhibiting aromatase. By inhibiting aromatase, the conversion process that is responsible for creating the active form of estrogen is blocked. This reduces levels of the active form of estrogen in the body so cancer cells are depleted of necessary growth stimulation. This is in contrast to tamoxifen, which blocks the growth stimulatory effects of estrogen by directly binding to estrogen receptors.
Anti-aromatase agents are classified into two groups, aromatase inhibitors and aromatase inactivators. Aromatase inhibitors transiently bind to the aromatase enzyme and aromatase inactivators permanently bind to the enzyme. Recently, results from clinical trials have demonstrated that anti-aromatase agents may delay cancer progression and improve survival with fewer side effects compared to tamoxifen in patients with metastatic ER-positive breast cancer.
Currently, two aromatase inhibitors, letrozole and anastrozole, are FDA-approved for the initial treatment of metastatic, ER-positive breast cancer in post-menopausal women. In addition, exemestane, an aromatase inactivator, is FDA-approved for women with metastatic breast cancer who have failed treatment with tamoxifen; however, current clinical trials are evaluating exemestane as initial treatment for patients with metastatic breast cancer.
There are still many questions regarding the use of anti-aromatase agents and many clinical trials are underway to address the clinical applications of this new type of hormonal therapy. Specifically, these trials are designed to directly compare hormonal agents; determine optimal duration of treatment with specific agents; evaluate combinations of hormonal therapy; evaluate the use of anti-aromatase agents in the adjuvant and preventive setting; and determine the efficacy of using anti-aromatase agents in pre-menopausal women.
Ongoing clinical trials will help establish the efficacy and safety of anti-aromatase agents. If these clinical trials continue to establish positive results, anti-aromatase agents could become more widely used for the treatment of ER-positive breast cancer. Women who have ER-positive breast cancer or who are at a high risk of developing breast cancer may wish to speak with their physician about the risks and benefits of treatment with aromatase agents or of participating in clinical trials designed to evaluate anti-aromatase agents. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and