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In this open\u2010label, single\u2010arm phase II trial, 25 patients were enrolled in 11 sites in Germany. Patients were stratified according to <jats:italic>PIK3CA<\/jats:italic> mutation status (tissue and cfDNA from serum samples) and\/or loss of PTEN expression. Patients received buparlisib (100\u00a0mg) and tamoxifen (20\u00a0mg) once daily on a continuous schedule (28\u2010day cycle) until progression or unacceptable toxicity.<\/jats:p><jats:p>Primary endpoint was overall 6\u2010month progression\u2010free survival (PFS) rate. Key secondary endpoints included the 6\u2010month PFS rate in subpopulations, PFS, overall survival, overall response rate (ORR), disease control rate (DCR), and safety.<\/jats:p><jats:p>Overall, the 6\u2010month PFS rate was 33.3% (n\/N\u00a0=\u00a07\/21, one\u2010sided 95% CI 16.8\u2010100) and median PFS was 6.1 (CI 2.6\u201010.6) months. The ORR and DCR were 12.5% and 44%. The <jats:italic>PIK3CA<\/jats:italic>\u2010mutated subgroup consistently showed the highest 6\u2010month PFS rate (62.5%, n\/N\u00a0=\u00a05\/8), median PFS (8.7\u00a0months), ORR (40%), and DCR (80%). No new safety signals emerged. Most common adverse events were gastrointestinal disorders (56%), psychiatric\/mood disorders (48%), skin rash\/hypersensitivity (44%), cardiovascular (40%), and hepatic (32%) events. The trial was prematurely terminated due to the substantially altered risk\u2010benefit profile of buparlisib. Nevertheless, <jats:italic>PIK3CA<\/jats:italic> mutations emerged as a clinically feasible and useful biomarker for combined PI3K inhibition and endocrine therapy in patients with HR<jats:sup>+<\/jats:sup> breast cancer. Further biomarker\u2010stratified studies with isoform\u2010specific PI3K inhibitors are warranted. <jats:italic>EudraCT No:<\/jats:italic> 2014\u2010000599\u201024.<\/jats:p>","DOI":"10.1002\/cam4.3092","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T18:41:52Z","timestamp":1588272112000},"page":"4527-4539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Buparlisib in combination with tamoxifen in pretreated patients with hormone receptor\u2010positive, HER2\u2010negative advanced breast cancer molecularly stratified for <i>PIK3CA<\/i> mutations and loss of PTEN expression"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-4385","authenticated-orcid":false,"given":"Anja","family":"Welt","sequence":"first","affiliation":[{"name":"Westdeutsches Tumorzentrum Innere Klinik (Tumorforschung) Universit\u00e4tsklinikum Essen Universit\u00e4t 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