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Contralateral breast cancers (CBC) are usually assumed to be new primary tumours. Understanding the patterns of occurrence of these entities, and\/or being able to reliably distinguish between the two, could have important implications for tailoring patient management at primary presentation and at IBTR\/CBC diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clonal relationship between index, and ipsilateral and contralateral subsequent breast tumours was assessed in 112 paired samples from two breast radiotherapy trials, IMPORT LOW and IMPORT HIGH, using copy number profiling and targeted sequencing of DNA. The spatial relationships between the index tumour beds, radiotherapy dose distributions and subsequent tumours were analysed via computational co-registration of cross-sectional imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the IMPORT HIGH cohort, where patients were at higher risk of IBTR, 61% of IBTRs were clonally related to the index tumour compared with only 32% from the IMPORT LOW cohort. There was no difference in the spatial distributions relative to index tumour beds of related compared to unrelated subsequent tumours. Related IBTRs occurred in a higher proportion of those diagnosed less than 5\u00a0years after index treatment, compared with those diagnosed after 5\u00a0years (66% vs. 24%). Four of 18 CBCs in the IMPORT HIGH cohort, but none from IMPORT LOW, were genomically similar to the index cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings show that IBTRs near the index tumour bed are not always true recurrences and also strongly suggest that some CBCs are metastases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13058-026-02232-9","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T13:01:05Z","timestamp":1777122065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic and spatial analysis of local recurrences following risk-adapted breast radiotherapy in the IMPORT trials"],"prefix":"10.1186","volume":"28","author":[{"given":"Sara V.","family":"Lightowlers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Roman-Escorza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceilidh","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.","family":"Bliss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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Both trials were approved by an appropriate ethics committee: IMPORT HIGH was approved by the Cambridgeshire Research Ethics Committee 4 (reference number 08\/H0305\/13) and IMPORT LOW was approved by the Oxfordshire Research Ethics Committee B (06\/Q1605\/128). All participants included in this research had consented to participate in the trials, and separately consented to inclusion in this sub-study.","order":1,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Additional consent for publication is not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Judith Bliss has received funding for research costs from Cancer Research UK, as well as research grants to the ICR-CTSU from Astra Zeneca, Merck Sharp & Dohme, Puma Biotechnology, Pfizer, Janssen-Cilag, Novartis, Eli Lilly, Breast Cancer Now, Breast International Group, Glaxo Smith Kline, Kortuc, NIHR and Verastem. All other authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"108"}}