European journal of cancer (Oxford, England : 1990)
October 14, 2026 · via Europe PMC
Combined pharmacologic and lifestyle intervention for breast cancer prevention: Results of the randomized phase II TOLERANT trial in high-risk women.
Serrano D, Lazzeroni M, Rizzo R, +20 more, Bonanni B
AI summary — for doctors, generated from the abstract only
In high-risk women, low-dose tamoxifen favorably shifted breast cancer risk-associated biomarkers, and intermittent caloric restriction added a complementary metabolic effect.
What was studied
Four-arm randomized phase II biomarker trial of 110 high-risk women for 6 months: low-dose tamoxifen (LDT), LDT plus intermittent caloric restriction (ICR), lifestyle intervention with step counter (LI), or LI plus ICR; primary endpoint was post-intervention SHBG, with LDT+ICR vs LI+ICR as the main comparison.
Key findings
- LDT with or without ICR significantly increased SHBG and IGFBP-3 and decreased IGF-I
- LI plus ICR was associated with higher SHBG than LI alone (p = 0.045)
- No differences in adverse events between arms, although LDT showed a mild but significant worsening in quality of life
Clinical relevance
Supports further study of combined pharmacologic and lifestyle prevention, but SHBG is not a validated surrogate for cancer risk reduction.
Who should care
Limitations
Phase II biomarker endpoints only, 6-month duration, modest sample size, and no cancer outcomes; some results are truncated in the abstract.
Biomarker changes are encouraging but do not demonstrate reduced breast cancer incidence.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
BACKGROUND
Breast cancer (BC) prevention strategies include lifestyle modification and preventive agents such as selective estrogen receptor modulators and aromatase inhibitors. Sex hormone-binding globulin (SHBG) is a breast cancer risk-associated biomarker; however, it is not a validated surrogate endpoint for breast cancer risk reduction.
METHODS
Population: women with hereditary BC risk, a ≥ 5% 10-year BC risk, or a history of intraepithelial neoplasia were enrolled.
TRIAL DESIGN
a four-arm randomized phase II biomarker trial: Tamoxifen 10 mg every other day (LDT); LDT + Intermittent Caloric Restriction (ICR); Lifestyle intervention with a step counter (LI); LI + ICR.
PRIMARY ENDPOINT
Post intervention levels of circulating SHBG. Secondary endpoints: modulation of IGF system, adipokines, inflammatory markers, quality of life. Main analysis was LDT+ ICR vs LI+ICR.
RESULTS
One hundred and ten participants were randomized to: LDT, LDT plus ICR, LI, or LI plus ICR, for 6 months. Mean age was 52 years and mean BMI was 25 kg/m²; 62% were unaffected carriers, and 65% were postmenopausal. LDT±ICR significantly increased SHBG and IGFBP-3 and decreased IGF-I (absolute change p 90%), LI plus ICR was significantly associated with higher SHBG compared with LI alone (p = 0.045). No differences in adverse events between arms; LDT demonstrated a mild, although significant, worsening in quality of life.
CONCLUSIONS
LDT favorably modulates BC risk-associated biomarkers, and ICR adds a complementary metabolic effect, supporting further investigation of these combined strategies.
DOI
10.1016/j.ejca.2026.117784
PMID
42892237
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
Want more like this?
Browse more from the feed. A free account unlocks the full feed, saving and communities.
Back to the research feed