Journal Article

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

Lazzeroni, Matteo, Nardi, Mariateresa, Macis, Debora, Aurilio, Gaetano, Mannucci, Sara, Bonanni, Bernardo, Buccolo, Simona, Zovato, Stefania, Briata, Irene Maria, Johansson, Harriet, Pensabene, Matilde, DeCensi, Andrea, Aristarco, Valentina, Sansone, Clementina, Guerrieri-Gonzaga, Aliana, Pistelli, Luigi, Serrano, Davide, Gnagnarella, Patrizia, Accornero, Chiara Arianna, Gandini, Sara

2024

Overview

Breast Cancer (BC) prevention strategies range from lifestyle changes such as increasing physical activity and reducing body weight to preventive drugs like tamoxifen, known to reduce BC incidence in high-risk women. Sex Hormone Binding Globulin (SHBG) is related to BC risk due to its ability to bind circulating estradiol at high affinity and to regulate estradiol action. A study protocol is presented based on the assessment of the effect of different interventions such as tamoxifen at 10 mg every other day (LDT), intermittent caloric restriction (ICR) two days per week, lifestyle intervention (LI, step counter use) and their combination on the modulation of SHBG and several other biomarkers associated to BC. A randomized phase II biomarker study will be conducted in 4 Italian centers. Unaffected women aged between 18 and 70 years, carriers of a germline pathogenetic variant (BRCA1, BRCA2, PALB2, or other moderate penetrance genes), or with a >5% BC risk at 10 years (according to the Tyrer-Cuzick or the Breast Cancer Surveillance Consortium Risk models) or with a previous diagnosis of intraepithelial neoplasia will be eligible. A total of 200 participants will be randomized to one of the four arms: LDT; LDT + ICR; LI; LI + ICR. Interventions will span six months, with baseline and follow-up clinic visits and interim phone calls. The aim of the study is to verify whether LDT increases circulating SHBG more than LI with or without ICR after 6 months. Secondary objectives include assessing HOMA-index, inflammatory markers, adiponectin/leptin ratio, quality of life (QoL), safety, toxicity, mammographic density, and changes in microbiome composition across groups. The study's innovation lies in its inclusion of diverse BC risk categories and combination of pharmaceutical and behavioral interventions, potentially enhancing intervention efficacy while balancing tamoxifen's side effects on QoL, especially menopausal symptoms. EuCT number:2023-503994-39-00; Clinical trials.gov NCT06033092.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 17β-Estradiol / Adiponectin / Adolescent / Adult / Aged / Analysis / Antineoplastic Agents, Hormonal - therapeutic use / Biology and Life Sciences / Biomarkers / Biomarkers, Tumor - blood / Body fat / Body mass index / Body weight / BRCA1 protein / BRCA2 protein / Breast cancer / Breast Neoplasms - prevention & control / Caloric Restriction - methods / Cancer therapies / Care and treatment / Clinical trials / Diagnosis / Diet / Dietary restrictions / Disease prevention / Dosage and administration / Exercise / Female / Globulins / Health aspects / Hormone replacement therapy / Humans / Hyperplasia / Insulin resistance / Leptin / Life Style / Lifestyles / Mammography / Medical innovations / Medicine and Health Sciences / Metabolism / Microbiomes / Middle Aged / Physical activity / Quality of life / Randomized Controlled Trials as Topic / Research and Analysis Methods / Risk factors / Sex Hormone-Binding Globulin - analysis / Sex Hormone-Binding Globulin - metabolism / Sex hormones / Side effects / Study Protocol / Tamoxifen / Tamoxifen - therapeutic use / Toxicity / Womens health / Young Adult