{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T22:44:18Z","timestamp":1787179458066,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>(1) Background: The management of ipsilateral breast cancer recurrence depends on the extent of the tumor, and staging results, and mastectomy is currently the standard of care for previously irradiated patients. Studies are increasingly investigating suitable candidates for the repeated use of breast-conserving approaches as an alternative to mastectomy. But this includes the crucial necessity for curative reirradiation (Re-RT). The therapeutic challenge in reirradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy, intraoperative radiotherapy, or external beam RT with photons or electrons. The application of particle therapy using proton beam therapy represents an innovative radiotherapeutic technique for breast cancer patients that might offer advantageous physical properties, a superior dose reduction to adjacent organs-at-risk, and effective target volume coverage with lower integral doses to the patient\u2019s whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses. (2) Methods: The BREAST trial (NCT06954623) will be conducted as a prospective, single-arm, phase II study in 20 patients with histologically proven invasive breast cancer recurrences after repeat breast-conserving surgery and with an indication for local reirradiation. The patients will receive partial-breast re-RT with proton beam therapy in 15 once-daily fractions up to a total dose of 40.05 Gy(RBE), delivered with active raster scanning. The required time interval will be 1 year after previous RT to the ipsilateral breast. (3) Results: The following results will be reported: The primary endpoint is defined as the cumulative overall occurrence of (sub)acute skin toxicity of grade \u2265 3 within 6 months after the start of re-RT. Secondary outcome includes an analysis of the local, regional, and distant control, progression-free and overall survival, quality of life, and cosmesis. The explorative and translational objectives of this study include planning comparisons to other RT techniques and irradiation types, dosimetric evaluations, analyses of radiological imaging features, and translational assessments of cardiac toxicity biomarkers and tumor markers. (4) Conclusions: Overall, the aim of this study is to evaluate the potential of proton beam therapy for partial breast reirradiation and to establish the underlying data for a randomized trial.<\/jats:p>","DOI":"10.3390\/jcm14103416","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T11:31:49Z","timestamp":1747135909000},"page":"3416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Partial Breast Reirradiation for Breast Cancer Recurrences After Repeat Breast-Conserving Surgery with Proton Beam Therapy: The Prospective BREAST Trial (NCT06954623)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7087-9581","authenticated-orcid":false,"given":"Eva","family":"Meixner","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-7150","authenticated-orcid":false,"given":"Semi","family":"Harrabi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Seidensaal","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Koczur","sequence":"additional","affiliation":[{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tessonnier","sequence":"additional","affiliation":[{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriane","family":"Lentz-Hommertgen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Hoeltgen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hoegen-Sa\u00dfmannshausen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"},{"name":"German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-7090","authenticated-orcid":false,"given":"Fabian","family":"Weykamp","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"},{"name":"German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Liermann","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"H\u00f6rner-Rieber","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69210 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"},{"name":"German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Department of Radiation Oncology, University Hospital D\u00fcsseldorf, 40225 D\u00fcsseldorf, 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