I am postmenopausal and have hormone-sensitive early breast cancer. I have been taking tamoxifen for two years. Should I switch to an aromatase inhibitor?
When the first aromatase inhibitor anastrozole (brand name Arimidex) was approved for use in the adjuvant setting in 2002, one of the initial questions discussed was: Should women stop taking tamoxifen and switch to Arimidex?
At the time, no one knew how to answer that question. There were no data. Now, we have findings from clinical trials that can help us assess the benefits of switching from tamoxifen to an aromatase inhibitor.
In August 2005 the Lancet published a combined analysis of data from two prospective trials, one carried out by the Austrian Breast and Colorectal Cancer Study Group and the other carried out by the German Adjuvant Breast Cancer Group. Both studies enrolled women with hormone-sensitive tumors (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive). And both randomized women into two groups. One group (1,606 women, total from both studies) took tamoxifen for five years. The other group (1,618 women, total from both studies) switched to Arimidex after two years of tamoxifen.
The researchers compared the two groups 28 months after the women either stayed on tamoxifen or switched to Arimidex. Among the 1,606 women on tamoxifen, 24 had a local recurrence, 75 had a distant recurrence (metastases), and 16 had cancer occur in the opposite breast. In contrast, among the 1,618 women who switched to Arimidex, 20 had a local recurrence, 46 had a distant recurrence, and 12 had a cancer occur in the opposite breast. There were 59 deaths in the tamoxifen group, 31 due to breast cancer, compared with 45 deaths, 24 due to breast cancer, among the women who switched to Arimidex.
These findings support the finding from a previous study published in the March 11, 2004, issue of the New England Journal of Medicine that found that women who switched to the aromatase inhibitor exemestane (brand name Aromasin) after two to three years on tamoxifen had less chance of experiencing a breast cancer recurrence than did women who remained on tamoxifen for five years.
This study enrolled 4,742 postmenopausal women who had been on tamoxifen for two to three years. Half of the women were randomly assigned to switch to exemestane, while the other half continued to take tamoxifen. The study found that there were 21 local recurrences, 114 distant recurrences (metastases), and 9 primary cancers in the opposite breast in the exemestane group compared with 33 local recurrences, 174 distant recurrences, and 20 primary cancers in the opposite breast in the tamoxifen group. In addition, there were 93 deaths in the exemestane group, 54 due to breast cancer, compared with 106 deaths in the tamoxifen group, 67 due to breast cancer.
Aromatase inhibitors have been found to have different side effects than tamoxifen, and that was seen in the Lancet study as well. In terms of potentially dangerous side effects, the study found that women on tamoxifen were more likely to experience a blood clot (12 women on tamoxifen compared with 3 on Arimidex) and to develop endometrial cancer (7 women on tamoxifen compared with 1 on Arimidex) while women on Arimidex were more likely to experience a fracture (34 on Arimidex compared with 16 on tamoxifen). Also, the women on tamoxifen were more likely to experience hot flashes (50 percent of the women on tamoxifen had hot flashes compared with 48 percent of the women on Arimidex) while the women on Arimidex were more likely to experience bone pain (19 percent of the women on Arimidex had bone pain compared to 16 percent of the women on tamoxifen).
In sum, it appears that using an aromatase inhibitor—either anastrozole (Arimidex) or exemestane (Aromasin)—after two years on tamoxifen reduces the risk of a cancer recurrence. However, the difference is really quite small. Also, we don't yet know whether switching actually saves lives. The results that we see right now are too small to be statistically significant. All three studies will have to follow the women longer for us to know whether aromatase inhibitors truly are better than tamoxifen in keeping breast cancer deaths from occurring.
So, should you switch?
If your risk for recurrence is low, or if you are at high risk for osteoporosis, it might make sense for you to stay on tamoxifen given that we know more about its long-term safety. Tamoxifen has been and remains a good option for many women. However, if your risk of recurrence is high, you should certainly consider switching to one of the aromatase inhibitors. I would recommend that you talk to your oncologist about your risk for recurrence, your risk for osteoporosis, and the side effects—if any—you have experienced while on tamoxifen. Only after that has been assessed and discussed can you and your doctor determine whether switching to an aromatase inhibitor is right for you.