Combined pharmacologic and lifestyle intervention for breast cancer prevention: Results of the randomized phase II TOLERANT trial in high-risk women.
Davide Serrano, Matteo Lazzeroni, Roberta Rizzo et al.
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In 30 seconds
The randomized phase II TOLERANT trial evaluated tamoxifen 10 mg every other day (low-dose tamoxifen, LDT), lifestyle intervention, and intermittent caloric restriction (ICR) in women at elevated breast cancer risk. Among 110 participants treated for 6 months, LDT, with or without ICR, increased circulating SHBG and IGFBP-3 and decreased IGF-I; ICR was associated with higher adiponectin than no ICR. In participants with greater than 90% adherence, adding ICR to lifestyle intervention was associated with higher SHBG than lifestyle intervention alone. SHBG is not a validated surrogate for breast cancer risk reduction.
Key findings
- LDT with or without ICR increased SHBG and IGFBP-3 and decreased IGF-I (absolute change p < 0.0001, p = 0.004, and p < 0.001, respectively).
- ICR arms had higher adiponectin than non-ICR arms (p = 0.003).
- Among participants with >90% adherence, lifestyle intervention plus ICR was associated with higher SHBG than lifestyle intervention alone (p = 0.045).
- Adverse events did not differ between arms; LDT was associated with a mild but significant worsening in quality of life.
Why it matters
The trial suggests that low-dose tamoxifen and intermittent caloric restriction may affect different breast cancer risk-associated biomarkers, providing a rationale for further study of combined prevention strategies. However, the primary endpoint was SHBG, which the authors note is not a validated surrogate for reducing breast cancer risk, so biomarker changes do not establish prevention of cancer.
What to keep in mind
This was a 6-month phase II biomarker trial, and SHBG is not a validated surrogate endpoint for breast cancer risk reduction.