Long-term Follow-up of the TAM-01 Study, a Phase III Trial of Low-dose Tamoxifen, and Pooled Analysis of Three Studies in Breast DCIS, High-risk Lesions and Microinvasive Disease

Detailed Summary

Low-dose tamoxifen (5 mg/day for three years, BabyTam) has emerged as a safer and effective alternative to the standard regimen (20 mg/day), reducing breast cancer recurrence with fewer adverse events. The TAM-01 phase III trial demonstrated a 42% reduction in breast cancer events over ten years compared to placebo in women with ductal carcinoma in situ (DCIS) or high-risk lesions (HRL, ADH, LCIS), supporting its inclusion in clinical guidelines. The phase III TAM-01 trial enrolled 500 women, comparing low-dose tamoxifen to placebo over three years, with a median follow-up of 9.7 years (IQR, 8.3-10.9). Results showed a significant reduction in invasive breast cancer (HR = 0.58; 95% CI: 0.35-0.95; p = 0.03) and in contralateral breast cancer, CBC (HR = 0.36; 95% CI: 0.14-0.92; p = 0.025), with no increase in serious adverse events. Exploratory analyses suggested a greater benefit in postmenopausal women (HR = 0.30; 95% CI: 0.11-0.82), compared to premenopausal women (HR = 0.73; 95% CI: 0.30-1.76), though this interaction did not reach statistical significance (p-interaction = 0.13). However, our unpublished data indicate a remarkable reduction of CBC in premenopausal women on BabyTam. The TAM-01 long-term follow-up study aims to extend the follow-up of TAM-01 participants, evaluating long-term outcomes, including incidence of invasive breast cancer and DCIS, with a focus on tumor laterality and menopausal status, as well as to assess other non-invasive events (LCIS, ADH, or ALH) and adverse outcomes of special interest. We will also perform a pooled analysis of our three low-dose tamoxifen studies to increase the statistical power of our findings, with special attention to the effect according to menopausal status and site of recurrence. The primary endpoint will be the breast cancer-free interval. The findings are expected to strengthen the evidence supporting low-dose tamoxifen as a viable prevention strategy in high-risk populations with intraepithelial neoplasia (IEN or DCIS+HRLs) or microinvasive disease.

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