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Review
. 2025 Jun 9;11(1):53.
doi: 10.1038/s41523-025-00745-8.

Window-of-opportunity trials to screen effective agents and optimize dose in breast cancer prevention

G Aurilio  1 , D Serrano  1 , M Lazzeroni  1 , A Guerrieri-Gonzaga  1 , H Johansson  1 , S Gandini  2 , I M Briata  3 , M D'Amico  3 , S Spinaci  4 , P Veronesi  5   6 , V Galimberti  5 , M Intra  5 , B M Heckman-Stoddard  7 , E Szabo  7 , G Viale  8   9 , B Bonanni  1 , A DeCensi  10
Affiliations
Review

Window-of-opportunity trials to screen effective agents and optimize dose in breast cancer prevention

G Aurilio et al. NPJ Breast Cancer. .

Abstract

Window-of-opportunity trials are a path to screen effective agents and optimize dose in breast cancer risk reduction. We review the scientific evidence regarding the utility of window-of-opportunity trials to screen effective agents and optimize dose for successful risk reduction/interception of breast cancer. Low-dose tamoxifen was evaluated in a window-of-opportunity trial and then validated in a phase-III trial. We are now studying similar activity with low-dose exemestane.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The WOO model reveals the field cancerization effect and may be relevant to preventive therapy.
A WOO study exploits the presence of a mammary field cancerization to draw signals on cancer tissue biomarker changes (red circles) and on adjacent pre-cancer lesions including DCIS/LCIS and ADH (blue circles). A main objective of a WOO study is to measure Ki-67 LI and percentage of precancer lesions to draw preventive activity of drugs.
Fig. 2
Fig. 2. Key points summarizing current evidence and strategies in endocrine prevention of breast cancer.
This figure outlines major concepts in endocrine prevention for high-risk breast cancer women. Topics include the clinical benefit and challenges of endocrine preventive therapy (A), dose optimization through window-of-opportunity trials (B), the role of Ki-67 LI as a prognostic biomarker (C), guideline-approved use of low-dose tamoxifen (D), novel dosing schedules of exemestane (E), and the FDA's project Optimus for dose selection standardization (F).
See this image and copyright information in PMC

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