Long-Term Use of Tamoxifen Increases the Risk of Uterine Cancer
The use of tamoxifen, an anti-estrogen drug, is commonly used to prevent a cancer recurrence in women with certain types of breast cancer. In many clinical trials, tamoxifen has been shown to decrease the risk of a cancer recurrence and increase overall survival in women with breast cancer that grow in response to the female hormone estrogen. However, the long-term use of tamoxifen is also associated with an increased risk of developing uterine cancer. According to a recent study published in The Lancet, the benefits of a decreased risk of a recurrence of breast cancer, attributed to the use of tamoxifen outweigh the risk of developing uterine cancer.
Breast cancer is characterized by the presence of cancer cells in the tissue or ducts of the breast. It is the second leading cause of cancer deaths in women in the United States. Depending on the extent of the disease, treatment options may include surgery, chemotherapy, radiation therapy and/or hormone therapy. Some breast cancers are referred to as
hormone receptor-positive, meaning the cancer cells utilize estrogen and/or progesterone (female hormones) for their growth. In an attempt to decrease the risk of a cancer recurrence, women with hormone receptor-positive breast cancer are often treated with the drug tamoxifen following surgery. Tamoxifen blocks estrogen from entering into a cancer cell, eliminating the source of growth for the cancer.
Although the use of tamoxifen may significantly reduce the risk of a cancer recurrence in women with hormone receptor-positive breast cancer, an increased risk for the development of uterine cancer is associated with it’s use. The uterus is a muscular organ located in the lower abdomen in females that serves as a womb for the fetus during gestation. The uterus is known to be very sensitive to hormones, but the exact mechanism in which tamoxifen facilitates the development of uterine cancer is not clearly understood.
In a recent clinical study, researchers from Holland evaluated the characteristics of uterine cancer associated with the use of tamoxifen. Data was collected from 309 women who had uterine cancer following breast cancer. Some of these women had received treatment with tamoxifen for varying lengths of time and some had never received tamoxifen. The rate of uterine cancer was clearly higher in the group of women that received tamoxifen, and the risk for developing cancer of the uterus increased with increasing duration of tamoxifen use. After 2-5 years of receiving tamoxifen, the risk for developing uterine cancer doubled and after 5 years of tamoxifen use the risk for developing uterine cancer increased by a factor of 7. Women with uterine cancer who received tamoxifen had more advanced cancers than women with uterine cancer who had not received tamoxifen. Survival from uterine cancer was worse for tamoxifen users compared to non-users. Three years following the diagnosis of uterine cancer, survival rates were 75% for women taking tamoxifen for 5 years or more, 85% for women taking tamoxifen for 2-5 years and 94% for women never taking tamoxifen.
The results of this clinical study are consistent with other studies demonstrating a correlation between long-term tamoxifen use and cancer of the uterus. It is important to emphasize, however, that the benefits associated with a decreased risk of a breast cancer recurrence in certain patients receiving tamoxifen may outweigh the risk for developing uterine cancer. It is important that women with hormone receptor-positive breast cancer thoroughly discuss potential risks and benefits of long-term tamoxifen treatment with their physicians before a decision is made. Persons with breast cancer may also wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating treatment with tamoxifen or other promising new treatment strategies.
(The Lancet, Vol 356, No 9233, pp 881-887, 2000)