Open Menu
Meetings & Education
Meetings & Education
Research & Data
Practice & Patients
Career Development
News & Initiatives
Get Involved
A phase II biomarker RCT in women at high risk for breast cancer: Low dose tamoxifen and lifestyle changes for breast cancer prevention (TOLERANT study).
Background:
Breast cancer (BC) prevention in high-risk women is crucial. Tamoxifen, despite its efficacy, has limited use due to its side effects. Low-dose tamoxifen (LDT) has shown much better balance between BC risk reduction and adverse effects. Additionally, lifestyle interventions (LI) like intermittent caloric restriction (ICR) and physical activity may further reduce BC risk by modulating factors such as mammographic density (MD) and sex hormone-binding globulin (SHBG) levels, which we showed is correlated with reduced breast cancer risk.
This study evaluates whether LDT increases circulating SHBG more effectively than LI with or without ICR after six months.
Methods:
The TOLERANT study is a randomized, four-arm, phase II trial involving 200 high-risk women recruited from four Italian hospitals. Participants will be randomly assigned to one of four intervention arms: (1) LDT, (2) LDT + ICR, (3) LI with step counter, (4) LI with step counter + ICR. Interventions will last six months, and participants’ adherence will be monitored through visits, telephone calls and diaries.
Eligible women are aged 18-70 with a high risk for BC due to genetic predisposition or a history of intraepithelial neoplasia. Key exclusion criteria include history of invasive BC, BMI <18.5, and certain medical conditions.
LDT involves 10 mg tamoxifen every other day. ICR follows a “5:2 diet” model, with five days of normal intake and two days at 25% of regular caloric intake. LI includes personalized advice and step counters targeting 10,000 steps per day.
Primary outcome is the change in SHBG levels. Secondary outcomes include changes in metabolic and inflammatory markers, QoL, body composition, microbiome diversity, and MD.
Blood and stool samples will be collected at baseline (B), three (3M), and six months (6M) to analyze biomarkers. Body composition will be assessed using bioelectrical impedance analysis, at B, 3M and 6M and MD will be measured in a subset of participants using digital mammography.
As of January 20, 2025, a total of 43 participants have been enrolled, including 18 with DCIS and 25 high-risk women.
The study, which has received approval from relevant ethics committees, will provide insights into the effectiveness of LDT and LI in reducing BC risk among high-risk women. The results could inform personalized prevention strategies, balancing efficacy with QoL.
Trial registration: EuCT number:2023-503994-39-00; Clinical trials.gov NCT06033092
Funding: 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. Co-PI Sara Gandini. The funders had no role in study design, data collection and analysis, or abstract preparation.
Reference*: Guerrieri-Gonzaga A et al. PLoS One. 2024 doi journal.pone.0309511
Disclaimer
This material on this page is ©2025 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Author Details
Sara Gandini
IEO, European Institute of Oncology IRCCS, Milan, Italy
Authors chevron_right
Associated Organizations chevron_right
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Prevention, Risk Reduction, and Genetics
Track
Prevention, Risk Reduction, and Genetics
View MoreAbstract Disclosure
open_in_new
Similar Abstracts
text_snippet
Abstract
2022 ASCO Annual Meeting
First Author: Ziwei Zhang
text_snippet
Abstract
2023 ASCO Annual Meeting
First Author: Takahiro Kogawa
text_snippet
Abstract
2023 ASCO Annual Meeting
First Author: Jian Yue
text_snippet
Abstract
2023 ASCO Annual Meeting
First Author: Stephanie L. Graff
Download
iframeBrand%3B24.0.0.0&uamb=0&uam=&uap=Linux%20x86_64&uapv=6.6.72&uaw=0&fledge=1&data=event%3Dgtag.config)
Your Privacy
ASCO is committed to transparency regarding our websites and the ways we process data. When you visit our site, we may store or retrieve information on your browser, mostly in the form of cookies. This information might be about you, your preferences, your location, or your device and is mostly used to make the site work as you expect it to and to personalize your web experience with us.
Because we respect your right to privacy, you can choose not to allow some or all types of cookies. Click on the different category headings to find out more about the types of cookies used on our websites and change your default settings to match your preferences. Please read these carefully. Blocking some types of cookies may impact your experience on the site, including our ability to personalize the content you receive from us.
For a full explanation of the personal and non-personal information we collect on our site, including how we use that information and your rights regarding that information, please review our Privacy Policy. Use of our website is also subject to our Terms of Use.
Allow All
Manage Consent Preferences
Essential Website Cookies
Always Active
These cookies are necessary for the website to function and are sometimes referred to as “strictly necessary” cookies. They make sure the website delivers you information and services in an optimal way.
They are often set in response to an action you take, such as changing your cookie preferences, setting your privacy preferences, logging in to our website, asking the site to remember you on subsequent pages, or filling in forms. These cookies do not identify you personally.
You can set your browser to block or alert you about all cookies, including essential website cookies, but some parts of the site will not work as a result.
Cookies Details
Performance and Functionality Cookies
Performance and Functionality Cookies
These cookies enhance the performance and functionality of our websites and the services we provide. For example, these cookies can keep track of your visitor session in between visits, enable you to share content through social media, use embedded media players, and use comment features. They also help us balance website load and improve site speed and performance.
All information these cookies collect is aggregated and therefore anonymous. These cookies may be set by us or by third party providers whose services we have added to our websites. These cookies are non-essential, but without these cookies, certain functionality or enhanced features may become unavailable.
Cookies Details
Personalization and Analytics Cookies
Personalization and Analytics Cookies
These cookies collect information that is used to help us understand how our websites and content are used, help us customize our websites and application for you in order to enhance your experience, and help us improve the content that ASCO creates to better meet our members’ and visitors’ needs. Examples include cookies that show us which content might be most popular with our visitors, understand browsing history of our users, understand the effectiveness of our own advertising, and enable us to recommend content to individual users based on their profile and activities on the website.
These cookies may be set by us or by third party providers whose services we have added to our websites.
These cookies are non-essential to the functionality of the site and may contain information that enables us or our third party providers to identify you and build a profile of your interests. Without these cookies, you will not be able to have a customized or personalized experience within our website.
Cookies Details
Advertising Cookies and Social Media Cookies
Advertising Cookies and Social Media Cookies
Advertising (or Targeting) cookies are third party cookies that may be set through our site by our advertising partners. They may be used by those companies to build a profile of your interests and show you relevant ads on other sites.
Social Media Cookies are cookies set by a range of social media services that we have added to the site to enable you to share our content with your friends and networks. They are capable of tracking your activities across other sites and building a profile of your interests. This may impact the content and messages you see on other websites you visit.
These cookies and the data collected by the third parties may be combined with data from other users or data about your activity on other sites. While the data collected on our site is aggregate or non-personal, the data may be used by such third parties to link you on other platforms or otherwise identify you.
If you do not allow these cookies, you may experience less targeted advertising.
Cookies Details
Back Button
Cookie List
Search Icon
Filter Icon
Clear
checkbox labellabel
ApplyCancel
ConsentLeg.Interest
checkbox labellabel
checkbox labellabel
checkbox labellabel
View Cookies
Name
cookie name
Save Settings
