{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:30:11Z","timestamp":1786617011828,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Guidelines in early breast cancer place adjuvant chemotherapy before radiotherapy, permit radiotherapy concurrently with endocrine and anti-HER2 agents, but discourage it before or during cytotoxic chemotherapy. This narrative review asks whether that convention remains defensible. Its historical basis, a single randomised trial whose distant-metastasis signal did not survive long-term follow-up, is weaker than is commonly assumed. Its contemporary basis is stronger and is stated here explicitly: an asymmetry of absolute benefit, in which a two-point gain in locoregional control yields roughly half a percentage point of mortality benefit once the EBCTCG four-to-one relationship is applied, whereas degradation of systemic therapy reaches mortality undiscounted. We specify three conditions under which a sequencing change could be justified and note that the absolute loss from a short chemotherapy delay cannot presently be quantified from randomised data. Meanwhile, chemotherapy has lengthened while radiotherapy has contracted to a one- to three-week whole-breast schedule, potentially extended when a sequential tumour-bed boost is required. The retrospective evidence is limited: one cohort offers a hypothesis-generating locoregional signal qualified by an unexpectedly high control-arm event rate and an unplanned subgroup analysis, while another supports only short-term feasibility and tolerability; neither demonstrates benefit in distant control or survival. We further argue that the population in which the question remains clinically live is narrow and probably contracting, since genomic de-escalation withdraws from chemotherapy the phenotypes with the most favourable arithmetic. Adjuvant sequencing is best regarded as an open, testable question within a defined population rather than a general case for change.<\/jats:p>","DOI":"10.3390\/medsci14040477","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:31:09Z","timestamp":1786613469000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemotherapy Before Radiotherapy in Adjuvant Breast Cancer: The Origins of a Convention and the Case for Revisiting Sequence in the Era of Hypofractionation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-0580","authenticated-orcid":false,"given":"Mihai-Teodor","family":"Georgescu","sequence":"first","affiliation":[{"name":"Oncology 2 Discipline, Department 8\u2014Radiology, Oncology, Hematology, Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG), Darby, S., McGale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., and Ewertz, M. 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