Low-Dose Tamoxifen Lowers Long-Term Breast Cancer Risk in DCIS: Study
Italy: Low-dose tamoxifen has been shown to reduce the long-term risk of breast cancer in women treated for ductal carcinoma in situ (DCIS). However, the magnitude of benefit varies according to menopausal status, suggesting that treatment outcomes may differ between premenopausal and postmenopausal women. These findings support the role of low-dose tamoxifen as an effective preventive strategy while highlighting the importance of individualized treatment decisions.
Although standard-dose tamoxifen (20 mg daily) effectively reduces breast cancer recurrence after noninvasive breast disease, its use is often limited by adverse effects. To determine whether lower doses could offer similar long-term protection with improved tolerability, researchers evaluated the efficacy of low-dose tamoxifen. Their findings, published in the Journal of Clinical Oncology, suggest that low-dose tamoxifen provides sustained long-term benefit, particularly in postmenopausal women with estrogen receptor-positive DCIS and other high-risk noninvasive breast lesions.
For the study, Sara Gandini and colleagues from the Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy, pooled individual-participant data from three clinical studies involving 1,545 women with estrogen receptor-positive or unknown DCIS, microinvasive carcinoma, or other high-risk breast lesions. Participants received low-dose tamoxifen (5 mg daily or 10 mg on alternate days for 2–5 years) or a control intervention. The primary endpoint was the first occurrence of any breast cancer event, including invasive breast cancer, recurrent DCIS, regional recurrence, or distant recurrence.
Key Findings
- After a median follow-up of 9.4 years, low-dose tamoxifen reduced overall breast cancer events compared with the control group.
- The treatment benefit varied according to menopausal status.
- In postmenopausal women, low-dose tamoxifen reduced the risk of breast cancer events by 49% (HR 0.51) and achieved an absolute 10-year risk reduction of 11.2%.
- In premenopausal women, low-dose tamoxifen did not significantly reduce overall breast cancer events or recurrence in the same (ipsilateral) breast.
- Low-dose tamoxifen reduced the risk of contralateral breast cancer by 55% (HR 0.45) in premenopausal women, indicating protection against new primary tumors.
- Serious adverse events were infrequent and occurred at similar rates in the low-dose tamoxifen and control groups, supporting the regimen's favorable safety profile.
The researchers acknowledged limitations, including the pooling of data from randomized clinical trials and a prospective cohort study, which may have introduced residual confounding. The study also had limited statistical power to detect menopausal subgroup differences for some secondary outcomes. However, consistent results across multiple sensitivity analyses strengthened the robustness of the findings.
The researchers concluded that low-dose tamoxifen is an effective, well-tolerated option for reducing long-term breast cancer risk in women with DCIS and other high-risk noninvasive breast lesions. However, the current evidence does not support replacing standard-dose endocrine therapy with low-dose tamoxifen for preventing ipsilateral recurrence in premenopausal women. Its significant reduction in contralateral breast cancer, however, highlights its potential as a personalized preventive strategy.
Reference:
DOI: 10.1200/JCO-26-00841
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