Dr. Susan Love Research Foundation | I am a premenopausal woman with early stage breast cancer. Can I use an aromatase inhibitor?

Aromatase inhibitors are hormone therapies that are used to treat women with hormone-positive (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive) tumors. Aromatase inhibitors work by blocking the aromatase enzyme, which converts androgens into estrogen. Although pre- and postmenopausal women can use tamoxifen as hormonal therapy, only postmenopausal women can use an aromatase inhibitor. That's because postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme. In contrast, premenopausal women get most of their estrogen directly from their ovaries (and aromatase inhibitors aren't able to block this estrogen).

Currently three aromatase inhibitors are approved for use by the US Food and Drug Administration (FDA): anastrozole (brand name Arimidex), letrozole (brand name Femara), and exemestane (brand name Aromasin).

In December 2004, the American Society of Clinical Oncology (ASCO) issued new guidelines on hormonal therapy. ASCO now recommends that most postmenopausal women be treated with an aromatase inhibitor. This means that tamoxifen, which has been used in the adjuvant setting since the 1980s, is no longer the standard of care for postmenopausal women. Tamoxifen does, however, remain the standard of care for premenopausal women.

For a premenopausal (still menstruating post chemotherapy) woman to take an aromatase inhibitor, she must have her ovaries removed (oophorectomy) or take a drug that will suppress ovarian functioning and decrease estrogen levels, putting her into menopause. The drugs most commonly used for this purpose are goserelin (brand name Zoladex), leuprolide (brand name Lupron), and triptorelin (brand name Trelstar).

Theoretically, an aromatase inhibitor should be as effective in a woman who is put into temporary menopause via one of these drugs as it is in a woman who has gone into menopause naturally. But we can't just assume that, which is why three important studies are now underway in Europe and the US to determine the optimal hormone treatment for, and the effectiveness of aromatase inhibitors in, premenopausal women. The three trials are called SOFT, TEXT, and PERCHE, or STP.

Investigators hope to recruit more than 6,000 women over the next five to seven years for these studies, which will play a critical role in determining which hormone therapies are recommended to premenopausal women in the future. Investigators expect to report preliminary data from these studies in 2008.

All three trials will use tamoxifen or the aromatase inhibitor exemestane along with triptorelin. Exemestane differs from the other aromatase inhibitors in that it stops the aromatase enzyme's production process permanently. This is why exemestane is often referred to as an aromatase "inactivator" rather than as an aromatase "inhibitor." Exemestane was selected because there are data from small studies that indicate it may be less likely to cause osteoporosis.

If you are interested in trying an aromatase inhibitor, I would suggest that you speak with your oncologist about enrolling in one of these trials. If there is no trial that is right for you, you and your doctor will need to discuss your risk for recurrence and the fact that we currently have no data on this treatment. This may be true for women whose tumors are HER2-positive, as there is some evidence that women who are both HER2-positive and ER-positive may have tumors that are resistant to tamoxifen but will respond to an aromatase inhibitor. (HER2 is also sometimes referred to as HER-2 or Her-2/neu or erb-b2.)

If you do decide to use an aromatase inhibitor as adjuvant therapy, you should have your bone density monitored during your treatment. Some oncologists recommend that premenopausal women try to decrease their risk of bone loss by also taking a bisphosphonate, a drug used to treat osteoporosis. You should speak with your oncologist about this as well. Whether you take tamoxifen or an aromatase inhibitor, I would encourage you to try to maintain your bone health by doing weight-bearing exercises. You should also make sure that you get adequate amounts of vitamin D and calcium in your diet, taking supplements if necessary.