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Breast cancer patients who switch to the aromatase inhibitor anastrozole (sold as Arimidex) after 2 years on tamoxifen do better than women who continue taking the full 5-year course of tamoxifen, results of a new analysis indicate. Writing in the Lancet, researchers from Austria and Germany report the combined findings of 2 recently completed studies.

The studies involved more than 3,000 postmenopausal women who received standard treatment for early-stage breast cancer (lumpectomy plus radiation or mastectomy) followed by tamoxifen. After 2 years on the drug, 1,608 women were randomly assigned to continue tamoxifen and 1,618 were assigned to switch to anastrozole.

Aromatase inhibitors and tamoxifen are types of hormone therapy that affect estrogen, which can cause breast cancer to grow. They only work in women whose tumors have hormone receptors; about 2/3 of breast cancer patients have these types of tumors. There are currently 3 aromatase inhibitors on the market: anastrozole, letrozole, and exemestane.

After about 28 months, women who took anastrozole had a lower risk of their cancer spreading or of a new cancer developing in the opposite breast compared to women who continued with tamoxifen. Nearly 96% of women on anastrozole were still cancer-free at that time, compared to almost 93% of women on tamoxifen.

There was no significant difference in overall survival between the groups after 3 years. As expected, however, the drugs did have different side effects. Women on anastrozole experienced significantly more bone fractures and significantly fewer blood clots than women on tamoxifen. Women on anastrozole also reported more bone pain and nausea.

Lead author Raimund Jakesz, MD, of the Vienna Medical University, says the findings support those of earlier trials -- particularly one called ATAC -- that showed aromatase inhibitors are better than tamoxifen at preventing breast cancer recurrences. That means women who have taken 2-3 years of tamoxifen should consider switching to an aromatase inhibitor for the remaining years of their treatment, he added.

That group of patients is likely getting smaller, said Christy Russell, MD, of the University of Southern California's Norris Comprehensive Cancer Center. Russell was not involved in the new research. She serves as chair of the American Cancer Society's Breast Cancer Advisory Group.

"I'd say since the ATAC data came out -- the head-to-head comparison of tamoxifen and anastrozole -- that any newly diagnosed postmenopausal woman with breast cancer has for the most part been started on anastrozole as her initial therapy," she said.

But are there some women who should get tamoxifen first, despite the fact that aromatase inhibitors seem to work better?

"There's no reported trial that has answered that question," said Russell.

But women who get breast cancer before they reach menopause may be candidates for taking tamoxifen first, Russell said. That's because aromatase inhibitors don't work in premenopausal women. Many doctors would start such a woman on tamoxifen, and only switch her to an aromatase inhibitor if she goes into permanent menopause -- either naturally or because of her breast cancer treatment.

The question of side effects also causes some doctors to start women on tamoxifen rather than an aromatase inhibitor, Russell said.

"The concerns being raised by physicians are for women with severe osteoporosis or who have already had fractures because we know there are more fractures on aromatase inhibitors," she explained.

Russell, however, thinks the benefits of aromatase inhibitors are greater than the risks to bone health, even in women at high risk for bone problems, such as the elderly. These women can be given other drugs like bisphosphonates to build bone strength while they're on an aromatase inhibitor, she said.

Moreover, Russell noted, elderly women are also at higher risk for blood clots and strokes -- and tamoxifen can increase this risk even more.

The ongoing Breast International Group 1-98 (BIG1-98) trial may provide some clarification about whether some women should stick with tamoxifen, Russell said. That study includes both a head-to-head comparison of the aromatase inhibitor letrozole and tamoxifen, as well as a comparison of women who take one of the drugs then switch to the other. Results are expected in a couple of years.

Citation: "Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of the ABCSG trial 8 and ARNO 95 trial." Published in the Lancet (Vol. 366, No. 9484: 455-462). First author: Raimund Jakesz, MD, of Vienna Medical University, Austria.