{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:56:00Z","timestamp":1790898960026,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009096","name":"Taiwan Clinical Oncology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009096","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Melissa Lee Cancer Foundation","award":["112DHA0100294"],"award-info":[{"award-number":["112DHA0100294"]}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CDK4\/6 inhibitors (CDK4\/6i) have shown great efficacy in prolonging progression-free survival and is the current standard of care for hormone positive (HR(+)) metastatic breast cancer (mBC). Despite well tolerability and ease of use, the most common side effect of CDK4\/6i is myelosuppression, with neutropenia the most prevalent adverse effect. Studies show that the prevalence and severity of neutropenia are more marked in Asian patients, although details remain obscure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, we retrospectively analyzed 105 Taiwanese patients who received palbociclib for HR(+) HER2(\u2212) mBC at the Taipei Veterans General Hospital. To investigate a possible genetic association for high prevalence of neutropenia, we queried the Taiwan Biobank with publicly available germline databases (ALFA, gnomAD, ExAC, 1000 Genomes project, HapMap), for the allele frequencies of 4 neutropenia-related SNPs (ABCB1_rs1045642, ABCB1_rs1128503, ERCC1_rs3212986, ERCC1_rs11615) and compared between different ethnicities. In addition, one of the patients was a long-term patient with peritoneal dialysis. We quantified the levels of palbociclib in her serum and peritoneal fluid by liquid chromatography-mass spectrometry (LC-MS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Interestingly, in our cohort, early neutropenia nadir (occurred within 56 days of start) was associated with worse treatment outcome, while occurrence of grade 3\/4 neutropenia was associated with better outcome. We observed an extremely high incidence of neutropenia (96.2% any grade, 70.4% grade 3\/4). In the analyzed germline databases, we discovered a higher SNP frequency of the T allele in ABCB1_rs1128503, a lower frequency of T allele in ABCB1_rs1045642, and a higher SNP frequency of G allele in ERCC1_rs11615. We observed that palbociclib levels in peritoneal dialysate ranged from around 20-50 ppb, and serum levels reached 100-110 ppb during drug administration and decreased to &amp;lt;10 ppb during discontinuation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our retrospective analysis of real world palbociclib use reveals an association with grade 3\/4 neutropenia with better outcome and early neutropenia nadir with worse outcome. Our findings of Asian specific SNPs support a predisposition toward profound and prevalent neutropenia in Asian patients under CDK4\/6i. We also report the first pharmacokinetics analysis on a patient with peritoneal dialysis receiving CDK4\/6i. In summary, our study provides novel clinical and genotypic insights into CDK4\/6i associated neutropenia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad304","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T21:01:24Z","timestamp":1700773284000},"page":"e455-e466","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and Genotypic Insights Into Higher Prevalence of Palbociclib Associated Neutropenia in Asian Patients"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-5466","authenticated-orcid":false,"given":"Jiun-I","family":"Lai","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Department of Medicine, National Yang-Ming Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Hao","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Jung","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Min Xuan","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Hsuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Department of Medicine, National Yang-Ming Ming Chiao Tung University , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-4731","authenticated-orcid":false,"given":"Chun-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Ming","family":"Tseng","sequence":"additional","affiliation":[{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chih","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, Department of Oncology, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Chung","family":"Chao","sequence":"additional","affiliation":[{"name":"Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"},{"name":"School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University , Taipei , Taiwan, Republic of China"},{"name":"Division of Cancer Prevention, Department of Oncology, Taipei Veterans General Hospital , Taipei , Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"2024041017254606600_CIT0001","first-page":"1925","article-title":"Palbociclib and letrozole in advanced breast cancer","volume-title":"N Engl J Med","author":"Finn","year":"2016"},{"key":"2024041017254606600_CIT0002","first-page":"1738","article-title":"Ribociclib as first-line therapy for HR-positive, 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