Tamoxifen carries a boxed warning, the FDA’s most prominent label alert, and the first thing it names is cancer of the uterus. The label also says that people already diagnosed with breast cancer mostly gain more from the drug than they risk. Both statements are true, and the work for doctors is holding them together.
The drug’s U.S. approval dates to 1977. It is a selective estrogen receptor modulator, according to the National Cancer Institute. In breast tissue it binds estrogen receptors and keeps estrogen from reaching them, which may stop cancer cells from growing. In bone it behaves like estrogen instead, which may increase bone mineral density. That split personality explains both the benefit and the trouble.
What the label says
The prescribing information lists three serious dangers: uterine malignancies, blood clots in the lung, and stroke. Fatal cases of each have occurred. The uterine problems are endometrial adenocarcinoma and uterine sarcoma. The label says the mechanism is unknown but may relate to tamoxifen’s estrogen-like effect.
Numbers come from the NSABP P-1 trial, which followed women with an elevated chance of developing breast cancer. Per 1000 women-years, endometrial adenocarcinoma ran at 2.20 for women on tamoxifen against 0.71 on placebo. Uterine sarcoma was 0.17 against 0.04. The absolute figures are small, but the gap between the groups is plain.
It also says uterine sarcoma was generally found at a later stage and had a poor prognosis. More long-term users, those on tamoxifen for 2 years or more, developed it than non-users did.
Who is told to watch for what
The instruction is plain. Any patient who is taking tamoxifen, or has taken it, and reports abnormal vaginal bleeding should be evaluated promptly. Annual gynecological examinations are advised. Patients should report irregular periods, a different discharge, or any pressure or pain in the pelvis. The label adds that no data suggest routine endometrial sampling helps in women with no symptoms.
WebMD, in a feature on managing hormone therapy, says tamoxifen can raise the odds of uterine cancer in women who have been through menopause. “In general, aromatase inhibitors are usually preferred for these patients,” said Jessica Jones, an oncology professor at the University of Texas medical school in Houston. Doctors typically prescribe tamoxifen to women who have not reached menopause, WebMD notes, and aromatase inhibitors after it.
Clots are rare but serious, she added. “For most people, the risk of having a clot while taking tamoxifen is extremely low,” Jones said, though anyone with a history of clots should not take it.
The benefit side
Erica Mayer, who directs breast cancer clinical research at Dana-Farber in Boston, told WebMD that hormone therapy is “extremely effective in reducing the risk of cancer recurrence anywhere in the body.” People typically stay on it for at least 5 years, and possibly up to 7-10 years. For most of them, she said, severe side effects are few.
Patients on tamoxifen who have concerns should take them to their own doctor before changing anything.
Sources
- Prescribing information highlights and warnings: tamoxifen citrate oral solution (FDA label via DailyMed)
- Tamoxifen Citrate (National Cancer Institute)
- Easing Tamoxifen, Aromatase Inhibitors Side Effects for Breast Cancer Treatment (WebMD)
