Extending Aromatase Inhibitor Treatment Time

Hormonal, anti-estrogen or endocrine therapies are effective systemic treatments for breast cancer in women who have estrogen receptor (ER) positive tumors. Like chemotherapy and unlike surgery or radiation therapy, they treat the whole body with the goal of eradicating any remaining cancer cells. ER-positive breast cancer cells require estrogen to proliferate, so starving them of this necessity is effective treatment.

The optimal duration of treatment with an AI has been more variable.

Younger, pre-menopausal women generally are given tamoxifen, a slightly different drug with the same effect. For them, the primary estrogen source in their bodies is their ovaries. Some younger women are treated with drugs to close down their ovaries and then take an aromatase inhibitor (AI). Older, post-menopausal women are usually given one of three AIs. After menopause, smaller amounts of estrogen are still produced by the adrenal glands, fat cells, breast tissue, and skin.

These two classes of drugs share a common purpose, starving cancer cells of estrogen, but work in different ways. Tamoxifen blocks the cancer cells’ ability to take in and use estrogen, sometimes called a lock and key effect, while the AIs reduce the amount of estrogen that is produced and make it less available to cancer cells. The three available AIs are Arimidex (anastrozole), Femara (letrozole), and Aromasin (exemestane). There are slight chemical differences among them, but they are equally effective. If a woman experiences unpleasant side effects from one of them, usually a switch to another solves the problem.

What is an AI? Aromatase is an enzyme that produces estrogen in fat cells. Note that this is the reason that being overweight is sometimes on the list of risk factors for both the initial development of breast cancer and a breast cancer recurrence. Women who have been diagnosed are counseled to maintain a healthy weight to reduce this risk. In post-menopausal women, most of the estrogen does not come from their no longer functioning ovaries. Instead, it is produced in the adrenal glands which produce something called a precursor steroid that is turned into estrogen; this process is helped by the aromatase enzyme. Drugs, like the AIs, that interfere with this process cause estrogen depletion, thereby starving the cancer cells of what they need to grow and divide.

Virtually all women who are diagnosed with ER-positive breast cancers are prescribed one or another endocrine therapy. As described above, younger women usually receive tamoxifen, and the usual duration of treatment is five years. Sometimes additional years of an AI are added, and, occasionally, the switch to an AI is made sooner. The optimal duration of treatment with an AI has been more variable. First available in 1995, these drugs were usually prescribed for five years, sometimes completing a total of five years after some time on tamoxifen, sometimes adding five additional years after tamoxifen and sometimes being the only drug prescribed. As time passed, some oncologists opted to keep their patients, at least those considered to be at higher risk of recurrence, on an AI for a longer time. Since the optimal duration of treatment has continued to be unclear, studies continue to be done to try to find an answer.

A recent international study was just reported in the New England Journal of Medicine. Almost 3500 women who had completed five years of treatment with an AI were assigned to either two or five additional years taking the drug. The conclusion was that five additional years was not more beneficial than two; the incidence of recurrence or death was the same in both groups. Additionally, the risk of bone fracture was greater in the group who remained on the drug for five more years.

This is not likely to be the final research into this question. Some women are eager to finish up the drug while others feel safer taking it for years. Some doctors worry about the possibility of late recurrences, sometimes years after the initial diagnosis, in women with ER-positive breast cancers and choose to maintain their patients on the drug for longer. Like most other things in Cancer World, this question becomes a necessary conversation between you and your doctor, and the reminder that everyone is different.