Tamoxifen

Use of tamoxifen* is associated with an increased risk of endometrial cancer. This increase in risk is seen in:

• women with breast cancer who take tamoxifen as adjuvant treatment (to reduce the risk of breast cancer coming back) and
• women at high risk of breast cancer who take tamoxifen to reduce their risk of developing breast cancer.

The risk of endometrial cancer in women using tamoxifen as adjuvant treatment for breast cancer has been measured in different ways. Some studies have compared women taking tamoxifen with those who do not take tamoxifen. Other studies have compared women who take tamoxifen with those who take a different medicine to reduce their risk of breast cancer coming back (for example, an aromatase inhibitor^#). The risk of endometrial cancer was consistently higher in women taking tamoxifen. The risk of endometrial cancer increases with longer use of tamoxifen. In women who take tamoxifen for 10 years, the risk of endometrial cancer is twice as high as the risk in women who take tamoxifen for 5 years.

The risk of endometrial cancer is about 3 times higher in postmenopausal women who take tamoxifen compared with women taking aromatase inhibitors for breast cancer treatment. Changing to an aromatase inhibitor instead of continued treatment with tamoxifen is also associated with a lower risk of endometrial cancer compared with long-term tamoxifen treatment.

Taking tamoxifen is an important adjuvant therapy and women should balance the important benefits of reducing breast cancer recurrence with any rare side effects including the increased risk of endometrial cancer.

An increased risk of endometrial cancer has also been seen in women who take tamoxifen to reduce their risk of breast cancer. The risk of endometrial cancer doubles as a result of taking tamoxifen. These studies have only shown an increase in endometrial cancer risk in women older than 50 years of age.

The association between tamoxifen and increased risk of endometrial cancer is likely to be due to hormones. Although tamoxifen blocks the effects of the female hormone oestrogen in breast cells, it has effects that are similar to oestrogen in the uterus. This is likely to contribute to an increased risk of endometrial cancer.

Raloxifene

Taking raloxifene is not associated with risk of endometrial cancer.

In studies of women taking raloxifene to reduce the risk of breast cancer, no change in the risk of endometrial cancer has been seen.

Raloxifene works in a different way to tamoxifen. Unlike tamoxifen, it does not have effects on the uterus that are similar to oestrogen.

*Selective oestrogen receptor modulators (SERMs) are medicines used in the treatment and prevention of breast cancer.

• Tamoxifen is a type of SERM therapy that is used in addition to other treatments for breast cancer to reduce the risk of breast cancer coming back after treatment. It is also used to reduce the risk of breast cancer in women at high risk of breast cancer. Tamoxifen can be used regardless of whether women have reached menopause.
• Raloxifene is another type of SERM therapy that is used to reduce the risk of breast cancer in women at high risk. It is also used to prevent and treat osteoporosis. Raloxifene is only used by women who have reached menopause. 

^#Aromatase inhibitors such as anastrazole and letrozole are a different type of hormone therapy used in the treatment of oestrogen-receptor positive breast cancer in postmenopausal women, and are used as an alternative to tamoxifen or in sequence after tamoxifen.