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Pathol. Oncol. Res. 29:1611369 .  \ndoi: 10.3389/pore.2023.1611369  \nCOPYRIGHT  \n© 2023 Tornyi, Árkosy, Horváth and Furka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nA new perspective on the proper timing of radiotherapy during CDK4/6 inhibitor therapy inpatients with “bone-only”metastatic breast cancer  \nIlona Tornyi 1, Peter Árkosy 2, Ildikó Horváth 1* and Andrea Furka 2,3  \n1Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 2Department of Oncology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 3Department of Clinical Radiology, Faculty of Health Care, Institute of Practical Methodology and Diagnostics, University of Miskolc, Miskolc, Hungary  \nThe vast majority of hormone positive and HER2 negative advanced breast cancers can be controlled well by endocrine therapy combined with the groundbreaking use of CDK4/6 inhibitors in the metastatic first-line setting. Approximately 50%–60% of these patients have “bone-only” metastatic disease. In oligometastatic cases or if a certain number of uncontrolled lesions develop during the aforementioned therapy, ablative radiotherapy can be delivered or, in symptomatic cases, urgent irradiation is needed with palliative intent. To achieve the most effective results, parallel with good quality of life, the timing of radiotherapy must be determined precisely, taking into account that different cell cycles are involved during different treatment modalities; therefore, optimization of treatment schedules ensures longer and safer post-progression overall survival. The key question is whether the two treatment modalities are safe concurrently or whether they should be administered separately, and if so, what is the optimal sequence and why? This manuscript aims to answer this important question, with a focus on quality of life. Existing publications focus on safety and toxicity profiles, and efficacy is detailed only tangentially and minimally.  \nKEYWORDS  \nbreast cancer, radiotherapy, radiosensitivity, CDK4/6 inhibitors, treatment timing  \nIntroduction  \nBreast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related mortality in women, worldwide [1] . The vast majority, approximately 75% of breast cancer patients, belongs to hormone-positive subtypes, with a relatively good prognosis [2]; thus, endocrine therapy is a highly effective treatment for these patients. Approximately 30% of women with an early-stage breast cancer diagnosis develop metastasis [3] . The metastatic site depends on the pathological subtype of the  \nPathology & Oncology Research 01 Published by Frontiers  \nprimary tumor, but in breast cancer, 30%–60% have metastases in the bone, 21%–32% in the lung, 15%–32% in the liver, and 4%–10% in the brain based on the SEER database [4] . Only 13% of primary breast cancer patients who developed metastasis in the bone survived >5 years in a Danish population-based cohort study [5] .  \nNew targeted drugs had to be develop","cbCaiggxY0xfkYef","https://ap.wps.com/l/cbCaiggxY0xfkYef","pdf",819323,"English","# Introduction\n## Breast cancer background and metastatic patterns\n## Endocrine therapy and role of CDK4/6 inhibitors\n## Rationale for combining radiotherapy with CDK4/6 inhibitors\n## Key research question and manuscript aims","[{\"question\":\"Why is radiotherapy timing important during CDK4/6 inhibitor therapy?\",\"answer\":\"Timing must be determined precisely to optimize outcomes and maintain quality of life. Different treatment modalities involve different cell cycles, so schedule optimization can support longer and safer post-progression overall survival.\"},{\"question\":\"What clinical scenario does the manuscript focus on?\",\"answer\":\"It focuses on patients with “bone-only” metastatic breast cancer treated with CDK4/6 inhibitors, where radiotherapy may be needed for oligometastatic progression or for urgent symptomatic palliation.\"},{\"question\":\"What is the central question the manuscript aims to answer?\",\"answer\":\"The key question is whether radiotherapy and CDK4/6 inhibitors can be administered safely at the same time or should be given separately, and if separated, what sequence is optimal and why.\"}]","A new perspective on the proper timing of radiotherapy during CDK4/6 inhibitor therapy in patients with bone-only metastatic breast cancer | PDF",1790229605]