Low-dose tamoxifen, or what many doctors call “Babytam,” can prevent breast cancer recurrence among people with high-risk lesions, such as people with ductal carcinoma in situ (DCIS) or those who have not had breast cancer but are at high risk. Follow-up results presented at the San Antonio Breast Cancer Symposium (SABCS) on December 9 show long-term benefit and could lead to a change in the standard of care for these groups.
The hormonal therapy tamoxifen treats breast cancer and prevents recurrence by blocking estrogen. It is given to people with hormone receptor-positive (HR+) breast cancer or those who are at high risk of developing breast cancer. Tamoxifen belongs to a category of medications called selective estrogen receptor modulators (SERMs).
A standard dose of tamoxifen is usually 20 to 40 mg. daily. At these doses, tamoxifen can cause side effects similar to the ones women have during menopause, such as hot flashes, vaginal dryness, and fatigue. These side effects can worsen quality of life, and in some cases cause people to stop taking the medication despite its powerful impact on prevention. This line of research looks at whether a lower dose might be as effective in preventing cancer without the side effects.
The TAM-01 phase III clinical trial began in 2008. It included 500 participants from 14 sites in Italy. They were all 75 or younger, with a mean age of 54. All had high-risk lesions such as:
- Atypical ductal hyperplasia (ADH) — abnormal cell growth in a breast duct that increases risk of developing DCIS or invasive breast cancer
- Lobular carcinoma in situ (LCIS) — abnormal cell growth in the breast lobules that increases risk of developing invasive breast cancer
- Ductal carcinoma in situ (DCIS) — noninvasive stage 0 breast cancer
The participants were randomized to take 5 mg tamoxifen or placebo, an inactive pill, daily for three years. They were followed for another seven years to see if they developed invasive breast cancer or DCIS. All received quality-of-life check-ins every six months for three years and annual mammograms for the full 10 years.
In 2018, the researchers reported that low-dose tamoxifen reduced breast cancer events (invasive cancer or DCIS) after a median of five years by 52% and contralateral breast cancer (cancer in the breast opposite a breast that had cancer) by 76%. The only side effect reported was one additional hot flash per day compared to the placebo group.
Based on these results, the National Comprehensive Cancer Network began recommending low-dose tamoxifen to prevent recurrence in people with DCIS. In addition, the American Society of Clinical Oncology and the U.S. Preventive Health Services Task Force guidelines now include low-dose tamoxifen as a preventive strategy for high-risk lesions.
The new 2022 report reflects 10 years of follow-up. These results confirm the benefit observed four years ago. There was a 42% overall reduction in breast cancer events. This includes a 32% reduction in ipsilateral (same-side) breast cancer and a 64% reduction in contralateral breast cancer. Among people who had DCIS, there was a 50% lower risk of recurrence with low-dose tamoxifen, suggesting this could be the new standard of care for this group.
Participants experienced no real side effects on low-dose tamoxifen, beyond the slight increase in hot flashes noted in 2018. Unlike full-dose tamoxifen, the 5-mg dose does not increase risk of cataracts or endometrial polyps.
The researchers will continue to analyze these results for specifics such as smoking and menopause status, although the relatively small size of the study makes it hard to look at subgroups. For this reason or due to the racial demographics of Italy, which is 95% white, the presenter did not share any findings related to race or ethnicity.
What this means for you
If you have been told by a doctor that you are at increased risk of breast cancer due to high-risk lesions or DCIS, this study provides important new information about the dose of tamoxifen you can take to prevent breast cancer. If you are already taking a higher dose of tamoxifen for this purpose, with difficult side effects, this may be especially welcome news. Because these results may change the standard treatment for such situations, talk with your healthcare provider about what the news may mean for you.
In a related talk at the 2022 Alamo Advocate Program, Olufunmilayo (Funmi) Olopade, MD, FACP, said that the takeaway message is that “more is not necessarily better,” adding that the 5-mg dose causes almost side effects.
Andrea De Censi, MD, who led the study, suggested that future studies might focus on even smaller doses. He is also interested in studying low-dose tamoxifen versus low-dose exemestane, an aromastase inhibitor, in high-risk postmenopausal women.
It is important to note that the 5-mg dose used in this study is not currently on the market. Dr. De Censi said that taking 10 mg on alternate days could be “a reasonable choice” because the drug stays in the system. If you are considering low-dose tamoxifen, talk with your doctor about your options.
Our 2022 SABCS coverage
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- Enhertu continues to show good results
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- Strengthening cancer care through communication
- Elacestrant on course to gain FDA approval
- Talking about racial disparities, pushing for solutions
- New breast cancer drug targets AKT pathway
- Research looks to avoid overtreatment in early-stage breast cancer
- Ibrance adds no benefit over Faslodex alone
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