{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:52:54Z","timestamp":1786135974460,"version":"build-2736575974"},"reference-count":53,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Metronomic chemotherapy with oral capecitabine + vinorelbine (Cape + VNL) provides synergistic cytostatic activity and antiangiogenic and immunomodulatory effects, potentially offering prolonged disease control with limited toxicity in HER2-negative metastatic breast cancer (MBC). However, efficacy in the real-world (RW) setting, especially in late lines, and the impact of dihydropyrimidine dehydrogenase (\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      ) polymorphisms on dose reduction and safety remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In this retrospective study, 200 patients with human epidermal growth factor receptor 2 (HER2)\u2013negative MBC were treated at the ASST Cremona Hospital (2015-2023) with metronomic Cape (1000 mg twice daily, in normal metabolizers; 500 mg twice daily, in\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      variant carriers) + VNL (20 mg\/day, once daily, 5-days-on\/2-days-off). All patients underwent pretreatment\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      genotyping and dose adjustment. Treatment was administered in the second-to-fourth setting. The primary end point was time-to-next treatment or death (TNTD); secondary end points included overall survival (OS), disease control rate (DCR) \u226524 weeks, overall response rate (ORR), safety, and genotype-toxicity correlations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The median age was 61 years, and\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      variants were present in 14.5% of patients; 34%, 41%, and 25% received therapy as second-, third-, and fourth-line treatment. The median TNTD was 22.0 weeks, and the OS was 64.0 weeks. The DCR was 38.5%, and the ORR was 22.0%. Efficacy was comparable between\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      variant carriers and normal metabolizers (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      values &gt; .05). In later lines, Eastern Cooperative Oncology Group performance status 2 and &gt;2 metastatic sites were independent negative prognostic factors (all values\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .05). Overall, 7.5% grade 3 toxicities occurred, especially in variant carriers without dose reduction and grade 4-5 events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      These RW data suggest that metronomic Cape + VNL may represent a clinically active and manageable option in heavily pretreated HER2-negative MBC. Our findings support prospective evaluation of\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      -guided dose individualization as a strategy to optimize the benefit-risk balance of fluoropyrimidine-based metronomic regimens.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00273","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:59:11Z","timestamp":1786132751000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["<i>DPYD<\/i>\n                    -Guided Dosing of Metronomic Capecitabine Plus Vinorelbine in Metastatic Human Epidermal Growth Factor Receptor 2\u2013Negative Breast Cancer: A Real-World Retrospective Study"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6561-1919","authenticated-orcid":true,"given":"Francesco","family":"Schettini","sequence":"first","affiliation":[{"name":"Clinic Barcelona Comprehensive Cancer Center, Hospital Clinic Barcelona, Barcelona, Italy"},{"name":"Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandro","family":"Membrino","sequence":"additional","affiliation":[{"name":"Multidisciplinary Oncology Unit and Breast Unit, ASST of Cremona Hospital, Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6147-9655","authenticated-orcid":true,"given":"Giuseppe","family":"Di Grazia","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain"},{"name":"Department of Human Pathology \u201cG. 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