Abstract Introduction: Approximately 70% of the Brazilian population depends on the public healthcare system (Sistema Único de Saúde - SUS). However, only 16% of SUS users have access to mammography for breast cancer screening, which necessitates the evaluation of new strategies to reduce mortality from the disease, including expanding physical breast examination (PBE) by non-medical professionals. Within the primary healthcare network, the Community Health Agent (CHA) is a technical-level professional who performs activities through home visits. The primary objective of this study is to evaluate the effectiveness of screening actions based on PBE performed by CHA in reducing advanced tumors (Stage III and IV) and breast cancer mortality rates. Secondary objectives include comparing the number of breast cancer diagnoses between the groups, establishing the overdiagnosis rate, comparing cancer-specific survival, comparing overall survival, comparing the number of diagnostic procedures, assessing the interval between the first symptom and diagnosis, evaluating the interval between diagnosis and the start of treatment, and comparing the financial cost of diagnosis and treatment for breast cancer patients. Trial design: Multicenter, phase III, prospective, randomized clinical trial. The target population comprises women aged 40 years or older and users of SUS. The randomization process will be carried out based on the spatial analysis of each participating center, using sociodemographic information on women from each macroregion to verify the homogeneity of data between groups. Intervention: After randomization, CHA in each group underwent training at different times. CHA in the CG received guidance on breast cancer screening and prevention according to Ministry of Health recommendations, while CHA in the IG received the same guidance and participated in theoretical and practical training for PBE (only female professionals). Variables and data collection: An application was developed to be installed on mobile devices, which the CHA used during home visits. The graphical interface of the application was developed in Dart/Flutter. For the backend, Python programming language was used along with the Flask framework to create the Application Programming Interface (API) responsible for the communication between the database and the application. The MySQL software was used for the relational database. The variables used for building the application included sociodemographic data, lifestyle habits, medical history, information on previous examinations, and physical breast examination. Statistical analysis: For the analyses, the database will be exported to the REDCap (Research Electronic Data Capture) platform. The calculations were defined to detect a reduction in severe cases and mortality (10% and 20%, respectively). For this purpose, a sample power of 80% and a Type I error of 5% were adopted after adjusting for intraclass correlation and sampling effect (0.032 and 1.892, respectively). The calculations were estimated using nQuery software (version 9.1). For the city of Itaberaí, a population of 1,894 women was estimated in each group, resulting in a total of 3,788. Present and target accrual: The trial was activated in December 2022, and as of June 30th, 2023, 2,467 patients had been accrued. The study will last for 16 years, and the first data analyses will be conducted in 2024. Registration and ethical aspects: The trial is registered in ReBEC (Brazilian register): RBR-39vm2nd. Contact information: Prof. Dr. Ruffo Freitas-Junior, Federal University of Goiás, ruffojr@terra.com.br. Citation Format: Ruffo Freitas-Junior, Danielle Rodrigues, Rosangela Corrêa, Leonardo Soares. Breast cancer screening based on physical breast examination: ITABERAÍ randomized trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-02.