KEY TAKEAWAYS
- The study aims to determine if low-dose tamoxifen increases SHBG more than lifestyle interventions in women at increased risk for BC.
- The TOLERANT study combines drug and behavioral interventions to improve BC prevention and reduce tamoxifen side effects.
Breast cancer (BC) prevention strategies include lifestyle modifications like physical activity and weight management, and medications such as tamoxifen, known to reduce BC incidence in high-risk women. Sex Hormone Binding Globulin (SHBG) plays a role in BC risk by binding circulating estradiol, regulating its action.
Aliana Guerrieri-Gonzaga and the team aims to investigate the impact of different interventions on SHBG levels and other BC-related biomarkers. The interventions include low-dose tamoxifen (LDT), intermittent caloric restriction (ICR), lifestyle intervention (LI – step counter use), and their combinations.
The study will enroll 200 women aged 18 to 70 years, categorized as high-risk for BC due to various factors, including germline pathogenic variants (BRCA1, BRCA2, PALB2, or other moderate penetrance genes), a 10-year BC risk exceeding 5% (according to Tyrer-Cuzick or Breast Cancer Surveillance Consortium Risk models), or prior intraepithelial neoplasia diagnosis.
Participants will be randomly assigned to 1 of 4 intervention arms: LDT; LDT + ICR; LI; LI + ICR. The interventions will last for 6 months, with baseline and follow-up clinic visits, along with interim phone calls.
The study will assess whether LDT increases circulating SHBG levels more effectively than LI with or without ICR after 6 months. Secondary outcomes include evaluating changes in HOMA-index, inflammatory markers, adiponectin/leptin ratio, quality of life (QoL), safety, toxicity, mammographic density, and microbiome composition across the groups.
The TOLERANT study will explore a novel approach by including diverse BC risk categories and combining pharmaceutical and behavioural interventions. This approach holds the potential to enhance intervention effectiveness while mitigating tamoxifen’s impact on QoL, particularly menopausal symptoms.
This work is funded by European Union – Next Generation EU – PNRR M6C2 – Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN – Project Code: PNRR-MAD-2022-12376567 – PI Bernardo Bonanni.
The trial is sponsored by European Institute of Oncology.
Source: https://pubmed.ncbi.nlm.nih.gov/39226292/
Clinical Trial: https://clinicaltrials.gov/study/NCT06033092
Guerrieri-Gonzaga A, Serrano D, Gnagnarella P, et al. (2024). “Low dose TamOxifen and LifestylE changes for bReast cANcer prevention (TOLERANT study): Study protocol of a randomized phase II biomarker trial in women at increased risk for breast cancer.” PLoS One. 2024;19(9):e0309511. Published 2024 Sep 3. doi:10.1371/journal.pone.0309511
