A major new study has shown that the well-established benefits of tamoxifen treatment for estrogen receptor-positive breast cancer are increased when the therapy is given for 10 years instead of the standard five.
Findings from the large international study were presented at the San Antonio Breast Cancer Symposium and published at the same time in The Lancet.
Tamoxifen, known as a selective estrogen receptor modulator, is used to treat both metastatic and early-stage breast cancer, as well as to prevent the disease in women at high risk. It functions by binding to the estrogen receptor and blocking estrogen action.
For women who are premenopausal or perimenopausal, tamoxifen is standard treatment after primary therapies, such as surgery and chemotherapy. Postmenopausal women may be prescribed an aromatase inhibitor (AI), tamoxifen in sequence with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor. AIs are hormonal medicines used only for postmenopausal women.
Reason for the Study
Earlier research established that five years of tamoxifen provides greater protection against cancer return, or recurrence, and death than two years or none at all. Studies of tamoxifen treatment for more than five years have been inconclusive.
The researchers of the new clinical trial, known as ATLAS (Adjuvant Tamoxifen: Longer Against Shorter), wanted to determine the effects of extending tamoxifen treatment to 10 years.
The multi-center research was conducted in numerous countries, from the United Kingdom to the Middle East, Asia and South America. It included 12,894 women with early breast cancer who had completed five years of tamoxifen therapy. The participants enrolled in the trial between1996 and 2005.
A computer randomly assigned the women to stop tamoxifen at five years or continue to the 10-year mark. They received yearly follow-ups to document who stayed on tamoxifen, any breast cancer recurrence, new primary cancer, hospital admission or death. Long-term follow-up is continuing.
The researchers reported on breast cancer results in the 6,846 study participants who had estrogen receptor-positive disease.
- That group was split nearly evenly between those who stopped tamoxifen at five years (3,418 women) and those who continued for 10 years (3,428 women)
- 18 percent of the five-year group and 19 percent of the 10-year group were younger than 45 when diagnosed
- About 80 percent of the women assigned to continue for 10 years stayed on the medicine
Compared to the group with five years of tamoxifen treatment, women taking tamoxifen for 10 years had:
- Fewer breast cancer recurrences (21.4 versus 25.1 percent)
- Lower mortality from breast cancer (12.2 versus 15 percent)
- Reduced overall mortality (639 deaths vs. 722)
- Greatest improvements shown in second decade after diagnosis
- 25 percent lower recurrence rate
- 29 percent lower breast cancer mortality rate
Findings were reported after more than seven years of follow-up and looked at results from years 5 to 14 after the women were first diagnosed.
The risk of endometrial (uterine) cancer, a rare but serious side effect of tamoxifen, rose among women age 50+ in the 10-year group, but not among premenopausal women. Endometrial cancer is very treatable, so the cumulative risk for death was 0.4 percent for the 10-year group compared to 0.2 percent for the five-year group.
The researchers concluded that women with estrogen-positive breast cancer who stay on tamoxifen for 10 years will further reduce recurrence and mortality.
What This Means for You
You may be taking tamoxifen on a five-year schedule and now wondering whether you should stay on the medicine for 10 years. Or, if your tamoxifen therapy is completed, you might want to know if you should start it again.
Every woman’s situation is different, so talk with your oncologist about whether extending treatment is right for you. Some things to think about:
- Tamoxifen is beneficial for a long time, even when taken for only five years
- The new study shows benefits can last longer with 10-year treatment
- Tamoxifen may cause side effects such as hot flashes, vaginal dryness and fatigue, which may be hard to tolerate
- Your healthcare team can offer ways to ease side effects so you will be able to stay on the medicine
- If your risk of recurrence is low (ask your doctor) but side effects are difficult, you might decide to take it for only five years
- Tamoxifen poses rare but serious risks such as blood clots and endometrial cancer
- Risks for most women are far less than the reduction of breast cancer deaths achieved through longer treatment
- Because tamoxifen can damage a fetus, you should not get pregnant while taking it. Adequate non-hormonal contraception is critical if you are premenopausal and taking tamoxifen—your doctor can help you.
- For family planning reasons, you might decide to stop tamoxifen after five years of treatment
- Many breast cancer experts believe this study will change the standard length of time for tamoxifen treatment, but others consider the gains to be only modest
- If you completed five years of tamoxifen and are now postmenopausal, your doctor may suggest you take an aromatase inhibitor for five additional years instead of tamoxifen
This study’s findings could apply to other hormonal therapies. Research is ongoing to see whether postmenopausal women would benefit from taking aromatase inhibitors for 10 years instead of the standard five. When that research is published, we will report it at lbbc.org.
C Davies, H Pan, J Godwin et al. Long-Term Effects of Continuing Adjuvant Tamoxifen to 10 Years Versus Stopping at 5 Years After Diagnosis of Oestrogen Receptor-Positive Breast Cancer: ATLAS, a Randomised Trial.The Lancet, early online publication, Dec. 5, 2012.
This article was supported by Cooperative Agreement Number DP11-1111 from The Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.