Tamoxifen and raloxifene

Tamoxifen and raloxifene
About tamoxifen and raloxifene

Tamoxifen and raloxifene are drugs that can be taken to lower your risk of breast cancer. They belong to a class of drugs known as selective estrogen response modifiers (or SERMs). This means that they act against the female hormone, estrogen, in some tissues of the body, but act like estrogen in others.

Both of these drugs act against estrogen in the breast, which is why they are useful in reducing the risk of breast cancer.
Tamoxifen

Tamoxifen is a drug originally used to treat a certain type of breast cancer and later found to be helpful in lowering the risk of breast cancer in some women. It is taken once a day, most often as a pill. It is sometimes known by the brand names, Nolvadex® and Soltamox™.

Tamoxifen works against breast cancer, in part, by interfering with the activity of estrogen. Estrogen is a female hormone that can fuel the growth of breast cancer cells. Tamoxifen blocks estrogen by keeping it from hooking up to receptors (molecules that control the cells’ activity) on cells in the breast. For this reason, tamoxifen is sometimes called an anti-estrogen. But actually, while it acts as an anti-estrogen in the breast, it acts like estrogen in other tissues, such as the bones and the lining of the uterus (the endometrium).

The main use of tamoxifen is to treat hormone receptor-positive breast cancer (breast cancer with cells that have estrogen and/or progesterone receptors on them). In patients with advanced breast cancer (that is hormone receptor-positive), tamoxifen shrinks tumors and helps patients live longer.

When given after a hormone receptor-positive cancer has been completely removed by surgery, tamoxifen lowers the chance that the cancer will come back later and helps patients live longer. It also lowers the chance that a new cancer will develop in the other breast.

Because tamoxifen was able to lower the chance of a new breast cancer occurring in women with breast cancer, doctors tested it to see if it could lower the chance of breast cancer in women at risk for, but with no history of the disease. Studies showed that tamoxifen could lower the risk of breast cancer by up to 50% (one-half). This led to tamoxifen being approved by the Food and Drug Administration (FDA) to reduce the risk of breast cancer in women who have an increased risk of breast cancer (and are 35 or older).

This drug may be used by women whether or not they have gone through menopause. (See the section called “Weighing risks versus benefits” for more information.)

Tamoxifen is generally safe, but it can rarely cause some serious side effects. Its pro-estrogen effects can lead cancer of the uterus and problems with serious blood clots, including stroke.
Raloxifene

Raloxifene (Evista®) is a drug that was first approved by the FDA to prevent and treat osteoporosis in women past menopause.

Raloxifene is a SERM that helps make bones stronger by acting like estrogen in bone tissue. Like tamoxifen, it also acts as an anti-estrogen in breast tissue. Because it doesn’t act much like estrogen in the uterus, it has a much lower risk of causing cancer of the uterus than tamoxifen. It is also less likely to cause problems with serious blood clots.

Because it has less serious side effects, it was tested to see if it, too, could lower breast cancer risk. These studies showed that it works almost as well as tamoxifen, lowering the risk of breast cancer by up to about 40%. This led to the approval of raloxifene by the FDA to help reduce breast cancer risk in women who have an increased risk of the disease. It was also found to lower breast cancer risk in women who have osteoporosis but not an increased risk of breast cancer, so it is approved for this group as well.

It is only approved for use in women past menopause because it was only studied in these women.
How well do these drugs lower the risk of breast cancer?
Tamoxifen

Much of what we know about the effect of tamoxifen on breast cancer risk comes from the Breast Cancer Prevention Trial (BCPT). The BCPT was a large study done to see if tamoxifen could lower breast cancer risk. It began in the early 1990s and was sponsored by the National Cancer Institute (NCI).

In this study, more than 13,000 women who were at higher than average risk of breast cancer were assigned to 1 of 2 groups. Each group was to take a pill each day for 5 years. One group took tamoxifen and the other took a placebo (sugar pill), but neither group of women knew which pill they were taking.

After about 7 years total, the study found that, compared with the women taking the placebo, those who took tamoxifen had:

A lower risk of invasive breast cancer overall. The risk of breast cancer was cut in half during the first 5 years of the study (during the years of drug treatment), with less improvement in the next 2 years.
There were 145 cases of breast cancer in the tamoxifen group compared with 250 cases in the placebo group. The effect on risk was only seen for estrogen positive breast cancers, the rate of estrogen negative breast cancer was the same in both groups.
About one-third less risk of non-invasive breast cancer, such as ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
There were 60 cases in the tamoxifen group compared with 93 cases in the placebo group.

During the 7-year follow-up, there was no major difference in the risk of death from breast cancer between the 2 groups. Breast cancer caused 11 deaths in the placebo group and 12 in the tamoxifen group. The total number of deaths (from any cause) was also about the same between the groups.

A number of other studies have also looked at tamoxifen for breast cancer risk reduction, including the IBIS-I study, the Royal Marsden study, and the Italian Tamoxifen Prevention study. They showed reductions in risk of invasive breast cancer of 16 to 30%.

When data from all 4 of these trials were taken together, they showed that tamoxifen lowered the risk of invasive breast cancer by about one-third. Again, tamoxifen has no effect on estrogen receptor-negative breast cancers, but ER-positive cancers were decreased by 45% in these studies.

These studies did not show any effect on death rates, either from breast cancer or any other cause. The evidence clearly shows that tamoxifen can reduce the risk of estrogen receptor-positive breast cancer.
Raloxifene

Studies of raloxifene include the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, the Raloxifene Use for the Heart (RUTH) trial, and the Continuing Outcomes Relevant to Evista (CORE) trial. All of these studies compared raloxifene to placebo (sugar pill) in women past menopause.

Taken together, these 3 studies showed an overall reduction in invasive breast cancer risk of 59%, with about a 70% reduction in the risk of estrogen receptor-positive breast cancer.

The largest study to look at the effect of raloxifene on breast cancer risk was the STAR (Study of Tamoxifen and Raloxifene) trial. This study compared the effects of tamoxifen and raloxifene on breast cancer risk in more than 19,000 women past menopause who were at increased risk of breast cancer. Half were assigned to take tamoxifen and half were assigned to take raloxifene each day for 5 years. Both drugs reduced the risk of breast cancer (both invasive and non-invasive types), although tamoxifen seemed to reduce the risk more. Raloxifene seemed to be about 75% as effective