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BCs with different intrinsic subtypes prefer different sites for metastasis. These subtypes vary in the abundance of genetic alterations which may influence the localization of metastases. Currently, information about the relation between metastatic site and mutational profile of BC is limited. In this study, <jats:italic>n<\/jats:italic>\u2009=\u2009521 BC metastases of the most frequently affected sites (bone, brain, liver, and lung) were investigated for the frequency of <jats:italic>AKT1, ERBB2, ESR1, PIK3CA<\/jats:italic>, and <jats:italic>TP53<\/jats:italic> mutations via NGS and pyrosequencing. Somatic mutations were present in 64% cases. <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>TP53<\/jats:italic> were the most frequently mutated genes under study. We provide an analysis of the mutational profile of BCs and the affected metastatic site. Genetic alterations differed significantly depending on the organ site affected by metastases. <jats:italic>TP53<\/jats:italic> mutations were mostly observed in brain metastases (51.0%), metastases outside of the brain revealed a much lower proportion of <jats:italic>TP53<\/jats:italic> mutated samples. <jats:italic>PIK3CA<\/jats:italic> mutations are frequent in liver (40.6%), lung (36.8%), and bone metastases (35.7%), whereas less common in brain metastases (18.4%). The highest percentage of <jats:italic>ESR1<\/jats:italic> mutations was observed in liver and lung metastases (about 30% each), whereas metastatic lesions in the brain showed significantly less <jats:italic>ESR1<\/jats:italic> mutations, only in 2.0% of the cases. In summary, we found significant differences of mutational status in mBC depending on the affected organ and intrinsic subtype. Organotropism of metastatic cancer spread may be influenced by the mutational profile of individual BCs.<\/jats:p>","DOI":"10.1002\/gcc.23199","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T18:04:48Z","timestamp":1694023488000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Frequency of genetic alterations differs in advanced breast cancer between metastatic sites"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6731-187X","authenticated-orcid":false,"given":"Isabel","family":"Grote","sequence":"first","affiliation":[{"name":"Institute of Pathology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Poppe","sequence":"additional","affiliation":[{"name":"Institute of Pathology Hannover Medical School  Hannover 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