Aromatase Inhibitors Better Than Tamoxifen After Surgery for Early-Stage Breast Cancer

Reviewed study: "Aromatase Inhibitors Better Than Tamoxifen After Surgery for Early-Stage Breast Cancer" by P. Goss and others, San Antonio Breast Cancer Symposium, December 9, 2005, General Session 3

Is this for me? If you are post-menopausal and have hormone-receptor-positive breast cancer and are considering hormonal therapy, you might want to read this article.

Background and importance of the studies: If you are post-menopausal with hormone-receptor-positive, early-stage breast cancer, hormonal therapy plays an important role in your treatment after surgery (called adjuvant treatment). Hormonal therapy keeps estrogen from "turning on" breast cancer cell growth.

It can be difficult to decide which hormonal therapy to use first, whether (and when) to switch from one to another—and whether you should start taking another hormonal medication after you finish your first course of hormonal treatment. Clinical studies continue to test and compare many of these treatment options.

Although tamoxifen used to be the "one and only" choice, the U.S. Food and Drug Administration has approved the use of aromatase inhibitors for women with early-stage disease under specific circumstances:

• as the first hormonal therapy after surgery, taking Femara (chemical name: letrozole) or Arimidex (chemical name: anastrozole) for five years.
• after two to three years of tamoxifen, switching to Aromasin (chemical name: exemestane) for two to three years.
• after five years of tamoxifen, taking Femara for five years.

In the studies reviewed here, researchers compared different aromatase inhibitors to tamoxifen as the first treatment after surgery for early-stage breast cancer. Researchers also compared taking an aromatase inhibitor after taking tamoxifen to taking tamoxifen alone.

MA-17 Trial (Five Years of Femara After Five Years of Tamoxifen)

The MA-17 trial, first reported on in 2003, is an international study of 5,187 post-menopausal women who took either Femara or a placebo (a sugar pill that looked like Femara) after completing five years of tamoxifen. These women had early-stage breast cancer that was hormone-receptor-positive. After about two and a half years of follow-up, results showed that women who took Femara after taking tamoxifen for five years lowered their risk of recurrence (the cancer coming back) by 43%, compared to women who took a placebo after taking tamoxifen for five years.

Once those results were released, women who took the placebo were offered the opportunity to take Femara. At the 2005 San Antonio Breast Cancer Symposium, researchers presented results for the women in the MA-17 trial who had originally taken the placebo.

Study design: Of the 2,247 women who originally received the placebo in the MA17 trial, about 1,600 decided to switch to Femara and 613 women decided not to pursue further treatment. Keep in mind that all of these women had completed five years of tamoxifen, about two and a half years of placebo, and were cancer-free when they were given the option of switching to Femara.

Results: Femara after tamoxifen is better than just tamoxifen

The women who switched from placebo to Femara had a 69% reduction in the risk of recurrence, compared to the women who decided not to pursue treatment. These differences are statistically significant, meaning that the difference was likely due to Femara and not just to chance. This risk reduction happened even though the women hadn't taken any hormonal therapy for about two and a half years (when they were taking the placebo). The women who switched also had a 72% lower risk of the cancer spreading to another part of their body (metastasis) and a 53% increase in survival.

But the women who switched to Femara also had more broken bones and significantly more osteoporosis than the women who chose not to take Femara.

Conclusions: The researchers concluded that taking five years of Femara after five years of tamoxifen is better than five years of tamoxifen alone for post-menopausal women with early-stage, hormone-receptor-positive breast cancer.

Results: Longer is better when taking Femara

Another analysis was done on the findings from the MA-17 trial to see if taking Femara for a longer time offered any additional benefits.

The researchers looked at the risk of cancer coming back (recurrence) in women who had taken Femara for one, two, three, and four years. The researchers found that the longer the women took Femara, the lower their risk of recurrence:

• Women who took Femara for one year had a 48% reduction in risk.
• Women who took Femara for four years had an 81% reduction in risk.

For women who had completed a five-year course of tamoxifen followed by just placebo (no Femara), the risk of recurrence continued to increase over time.

The researchers concluded that women continue to be at risk for recurrence after finishing five years of tamoxifen. Femara reduces this risk. The longer a woman takes Femara (up to five years), the lower the risk.

ABCSG Trial 8, ARNO 95 Trial, and ITA Trial (Arimidex After Tamoxifen)

In October 2005, Breastcancer.org reported on two trials that compared findings for women who switched to Arimidex after two to three years of tamoxifen with findings for women who took tamoxifen for five years. These studies showed that women who switched to Arimidex for three years after taking tamoxifen for two years did better than those taking tamoxifen for five years. Switching reduced the risk of recurrence and the risk of developing a new cancer in the other breast.

At the 2005 San Antonio Breast Cancer Symposium, researchers presented additional findings from these two trials, the ABCSG Trial 8 and the ARNO 95 Trial. They also presented results from the ITA Trial. In all three trials, the researchers wanted to know if an increase in disease-free survival (how long women live without cancer coming back) from switching to Arimidex led to an increase in overall survival (how long women live, with or without the cancer returning).

Study designs: The designs of the three trials were similar. Post-menopausal women with early-stage, hormone-receptor-positive cancer who took tamoxifen for two to three years either continued taking tamoxifen or switched to Arimidex until they had completed five years of hormonal therapy. Of the 4,006 women in all three trials, 2,009 of the women switched to Arimidex and 1,997 stayed on tamoxifen. The average follow-up time was about two and a half years.

Results: The researchers found that women who switched to Arimidex had a 41% increase in disease-free survival, which was statistically significant. This means that the improved outcome was probably due to Arimidex, rather than just due to chance. The researchers also found that switching to Arimidex increased overall survival by 29%—also a significant difference.

Conclusions: The researchers concluded that post-menopausal women with hormone-receptor-positive breast cancer should switch to Arimidex for two to three years after two to three years of tamoxifen (for a total of five years of treatment).

BIG 1-98 Trial (Femara Compared to Tamoxifen)

In February 2005, breastcancer.org reported on the BIG 1-98 Trial comparing Femara and tamoxifen after surgery for women with early-stage, hormone-receptor-positive breast cancer. The early conclusions from the trial were that women who took Femara had a significantly lower risk of recurrence and improved disease-free survival compared to women who took tamoxifen.

At the 2005 San Antonio Breast Cancer Symposium, researchers presented results of another analysis of BIG 1-98 information, looking at whether progesterone receptor status affected the benefits of Femara.

Study design: The researchers looked at cancer samples from almost 4,400 women and determined their estrogen receptor and progesterone receptor status. They then analyzed whether the women had benefited from taking Femara.

Results: The researchers found that women got more benefit from taking Femara than from taking tamoxifen if their cancers were:

• estrogen-receptor-positive and progesterone-receptor-positive, and
• estrogen-receptor-positive and progesterone-receptor-negative.

This was about 96% of the women in the study. Only about 4% of the women in the study had breast cancer that was estrogen-receptor-negative.

Conclusions: The researchers concluded that Femara is beneficial for post-menopausal women with early-stage, estrogen-receptor-positive breast cancer, no matter what their progesterone receptor status is.

---

• Research News on Hormonal Therapy (44 Articles)