Q. I've been on tamoxifen for a couple of years, and now my doctor is switching me to an aromatase inhibitor. I understand how tamoxifen works, but this AI is a whole new thing... how does it work?

A. Aromatase inhibitors (pronounced aroma-tase: just like it looks) come in three basic flavors: Femara® (letrozole), Arimidex® (anastrozole), and Aromasin® (exemestane). They're all known as third-generation AIs, meaning they're the third round of this type of drug to be developed-and the most successful so far.

AI's are the current drug of choice for postmenopausal women with ER- or PR-receptive (estrogen or progesterone receptive) breast cancer-either following a 2-3 year course of tamoxifen, or right out of the gate, post-surgery/chemo/radiation.

So, how does an AI work, exactly? Aromatase is an enzyme that turns the hormone androgen into estrogen. No aromatase = no estrogen. No estrogen = breast cancer cells can't grow (in women with hormone-receptive cancer). An aromatase inhibitor does exactly what it says: it inhibits the enzyme from doing its job. How? By binding itself, either temporarily (Arimidex, Femara) or permanently (Aromasin) to aromatase so that it becomes dysfunctional, and can't turn androgen into estrogen.

Tamoxifen works by preventing estrogen from binding to breast cancer cells and helping them grow. But an AI will actually reduce the amount of estrogen in your body by 90% to 95% - though only in postmenopausal women, which is why AIs are only recommended for women who've stopped having their period. Women whose ovaries are still active, who are still menstruating, produce too much estrogen for AIs to be effective. Thus, the decision for a woman having hormone therapy to start right in on an AI (vs. taking tamoxifen for awhile) may depend on whether her chemotherapy-induced menopause is permanent, or only temporary. If permanent, her doctor might start her on an AI right away. If temporary, and she remains pre-menopausal, she's not a candidate for an AI.

Q. How does the doctor decide whether I should take Aromasin, Arimidex, or Femara? Are they basically all the same, just made by different drug manufacturers?

A. They're all similar, but not exactly the same. Aromasin binds permanently to aromatase. Arimidex and Femara can bind with aromatase, then let go (this is called "reversible binding.") But they're so aggressive that their presence in your body means they will invariably shoulder any aromatase out of the way-kind of like that pushy person who always manages to get a seat in musical chairs.

Understand that all of these third-generation AIs are still very new, and results of long-term clinical trials are barely starting to come in. Some of the larger clinical trials include testing the effectiveness of tamoxifen vs. Arimidex (the ATAC trial, completed in 2005); Femara given after 5 years of tamoxifen vs. no further treatment after 5 years of tamoxifen (MA-17 trial, ended prematurely in 2003 when the results clearly showed Femara reducing recurrence risk significantly); and 5 years of Femara vs. 5 years of tamoxifen, head to head (the BIG trial, completed in 2005). All three trials showed the AI having a significant advantage over tamoxifen. Remember, all of these trials involve post-menopausal women, NOT pre-menopausal.