Review Article Omission of postoperative radiation after breast conserving surgery: A progressive paradigm shift towards precision medicine Pierfrancesco Franco a,b,⇑ , Fiorenza De Rose c , Maria Carmen De Santis d , Nadia Pasinetti e , Valentina Lancellotta f , Bruno Meduri g , Icro Meattini h,i , Clinical Oncology Breast Cancer Group (COBCG) Investigators a Department of Oncology, Radiation Oncology, University of Turin, Italy b Department of Oncology, Radiation Oncology, AOU Citta’ della Salute e della Scienza, Turin, Italy c Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Rozzano, Italy d Radiation Oncology Department, National Cancer Institute, Milan, Italy e Radiation Oncology Department, University of Brescia and Spedali Civili, Brescia, Italy f Radiation Oncology Department, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy g Radiation Oncology Unit, University Hospital of Modena, Modena, Italy h Department of Experimental and Clinical Biomedical Sciences ‘‘M. Serio”, University of Florence, Florence, Italy i Radiation Oncology Unit – Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy article info Article history: Received 27 December 2019 Revised 2 February 2020 Accepted 2 February 2020 Available online 8 February 2020 Keywords: Radiotherapy omission Breast cancer Breast conserving surgery Low risk Endocrine therapy Whole breast irradiation Partial breast irradiation Elderly Radiation oncology abstract Radiation therapy is a standard therapeutic option in the post-operative setting for early breast cancer patients after breast conserving surgery, providing a substantial benefit in reducing the risk of local relapse with a consequent survival gain. Nevertheless, the reduction in the burden related to treatment is becoming crucial in modern oncology for both local and systemic therapies and investigational efforts are being put forward by radiations oncologists to identify a subset of women at very low risk to be potentially omitted from post-operative irradiation after breast conservation. Clinical factors, classical pathological parameters and new predictive scores derived from gene expression and next generation sequencing techniques are being integrated in the quest toward a reliable low-risk profile for breast can- cer patients. We herein provide a comprehensive overview on the topic. Ó 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents 1. Introduction ......................................................................................................... 113 2. Establishing the role of breast conservation and hormonal therapy............................................................. 113 3. First generation of phase III trials investigating WBI omission ................................................................. 113 4. Phase III trials investigating selective WBI omission in patients at low risk ...................................................... 115 5. Prospective trials using biomarker-based approaches to identify low risk patients ................................................ 116 6. Selective omission of endocrine therapy for patients treated with BCS and radiation .............................................. 117 7. Conclusions .......................................................................................................... 118 Declaration of Competing Interest ....................................................................................... 118 References .......................................................................................................... 118 https://doi.org/10.1016/j.ctro.2020.02.003 2405-6308/Ó 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ⇑ Corresponding author. E-mail address: pierfrancesco.franco@unito.it (P. Franco). Clinical and Translational Radiation Oncology 21 (2020) 112–119 Contents lists available at ScienceDirect Clinical and Translational Radiation Oncology journal homepage: www.elsevier.com/locate/ctro