{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:57:22Z","timestamp":1787684242611,"version":"build-2784847793"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Cyclin-dependent kinase 4\/6 inhibitors (CDK4\/6i) combined with endocrine therapy are recommended as first- or second-line treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or recurrent breast cancer. However, in clinical practice, initiation timing varies according to patient characteristics, prior treatments, and the choice of the physician. Thus, the optimal timing of combination treatment remains unclear. Materials and Methods: In this multicenter retrospective cohort study, we reviewed 66 female patients who received CDK4\/6i (palbociclib or abemaciclib) between March 2018 and November 2019. Patients were categorized into the first-line treatment (group A) (n = 21) and second- or subsequent-line treatment (group B) (n = 45) groups. In the latter group, endocrine therapy and\/or chemotherapy had been administered previously. Duration of treatment with CDK4\/6i (DOT), overall survival (OS), treatment duration of other regimens, and reasons for treatment discontinuation after CDK4\/6i treatment were compared between groups. Results: The median DOT was significantly longer in group A than in group B (23 months (95% CI, 8\u201343) vs. 7 months (95% CI, 3\u201315); p = 0.015, at log-rank test). OS showed no significant difference between the two groups (p = 0.69, at log-rank test). Conclusions: In patients with HR-positive, HER2-negative advanced or recurrent breast cancer, first-line use of CDK4\/6 inhibitors was associated with a significantly longer duration of treatment compared with second- or subsequent-line use. However, no significant difference in OS was observed between patients receiving CDK4\/6 inhibitors as first-line or second- or subsequent-line therapy.<\/jats:p>","DOI":"10.3390\/medicina62040661","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["First- Versus Second- or Subsequent-Line Use of Cyclin-Dependent Kinase 4\/6 Inhibitors for Hormone Receptor-Positive\/Human Epidermal Growth Factor Receptor 2-Negative Metastatic or Recurrent Breast Cancer: A Multicenter, Retrospective Cohort Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4136-5325","authenticated-orcid":false,"given":"Shoko","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal and Breast Surgery, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0878-7851","authenticated-orcid":false,"given":"Shigeru","family":"Imoto","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Isaka","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-4817","authenticated-orcid":false,"given":"Hirohito","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-9047","authenticated-orcid":false,"given":"Sota","family":"Asaga","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan"},{"name":"Department of Surgery, Keiyu Hospital, 3-7-3 Minatomirai, Nishi-ku, Yokohama City 220-8521, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-0560","authenticated-orcid":false,"given":"Shigehiro","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Breast Surgery, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1344-149X","authenticated-orcid":false,"given":"Kenji","family":"Koneri","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Breast Surgery, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6470-2848","authenticated-orcid":false,"given":"Hiroyuki","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Breast Surgery, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7671-0648","authenticated-orcid":false,"given":"Takanori","family":"Goi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Breast Surgery, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","unstructured":"National Comprehensive Cancer Network (2020). 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