{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:39:32Z","timestamp":1779205172096,"version":"3.51.4"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Support Care Cancer"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1007\/s00520-025-09625-0","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:09:05Z","timestamp":1750082945000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hepatotoxicity across CDK 4\/6 inhibitors: a Narrative Review"],"prefix":"10.1007","volume":"33","author":[{"given":"Wilfrid H. F.","family":"Wong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Vasiliu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"McFarlane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"9625_CR1","unstructured":"Canadian Cancer Society (2023) Breast cancer statistics. https:\/\/cancer.ca\/en\/cancer-information\/cancer-types\/breast\/statistics.\u00a0Accessed 5 Apr 2024"},{"key":"9625_CR2","unstructured":"Canadian Cancer Society (2023) Stages of breast cancer. https:\/\/cancer.ca\/en\/cancer-information\/cancer-types\/breast\/staging. Accessed 5 Apr 2024"},{"issue":"9","key":"9625_CR3","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.3390\/biom13091422","volume":"13","author":"IM Stanciu","year":"2023","unstructured":"Stanciu IM, Parosanu AI, Nitipir C (2023) An overview of the safety profile and clinical impact of CDK4\/6 inhibitors in breast cancer\u2014a systematic review of randomized phase II and III clinical trials. Biomolecules 13(9):1422. https:\/\/doi.org\/10.3390\/biom13091422","journal-title":"Biomolecules"},{"issue":"3","key":"9625_CR4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s40265-020-01461-2","volume":"81","author":"CL Braal","year":"2021","unstructured":"Braal CL, Jongbloed EM, Wilting SM, Mathijssen RHJ, Koolen SLW, Jager A (2021) Inhibiting CDK4\/6 in breast cancer with Palbociclib, Ribociclib, and Abemaciclib: similarities and differences. Drugs 81(3):317\u2013331. https:\/\/doi.org\/10.1007\/s40265-020-01461-2","journal-title":"Drugs"},{"key":"9625_CR5","unstructured":"Product Monograph (2024) Ibrance\u00ae. Pfizer Canada, Kirkland, QC"},{"key":"9625_CR6","unstructured":"Product Monograph (2023) Kisqali\u00ae.\u00a0Novartis Canada, Dorval, QC"},{"key":"9625_CR7","unstructured":"Product Monograph (2023) Verzenio\u00ae. Eli Lilly Canada, Mississauga, ON"},{"key":"9625_CR8","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.6004\/jnccn.2018.0200","volume":"16","author":"JC Chang","year":"2018","unstructured":"Chang JC, O\u2019Regan R (2018) Use of novel combination therapies in the treatment of advanced HR+\/HER2- breast cancer. J Natl Compr Canc Netw 16:S5\u2013S17. https:\/\/doi.org\/10.6004\/jnccn.2018.0200","journal-title":"J Natl Compr Canc Netw"},{"key":"9625_CR9","unstructured":"Cancer Institute N (2017)\u00a0Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. https:\/\/www.meddra.org\/. Accessed 5 Apr 2024"},{"key":"9625_CR10","unstructured":"Cancer Care Ontario (2021)\u00a0Ribociclib Product Monograph. https:\/\/www.cancercareontario.ca\/en\/drugformulary\/drugs\/monograph\/54136. Accessed 11 Apr 2024"},{"key":"9625_CR11","unstructured":"Cancer Care Ontario (2023) Abemaciclib Product Monograph. https:\/\/www.cancercareontario.ca\/en\/drugformulary\/drugs\/monograph\/62406. Accessed 11 Apr 2024"},{"key":"9625_CR12","unstructured":"Cancer Care Ontario (2021) Palbociclib Product Monograph. https:\/\/www.cancercareontario.ca\/en\/drugformulary\/drugs\/monograph\/44456. Accessed 11 Apr 2024"},{"issue":"1","key":"9625_CR13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1470-2045(14)71159-3","volume":"16","author":"RS Finn","year":"2015","unstructured":"Finn RS, Crown JP, Lang I et al (2015) The cyclin-dependent kinase 4\/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1\/TRIO-18): A randomised phase 2 study. Lancet Oncol 16(1):25\u201335. https:\/\/doi.org\/10.1016\/S1470-2045(14)71159-3","journal-title":"Lancet Oncol"},{"issue":"3","key":"9625_CR14","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s10549-018-05125-4","volume":"174","author":"HS Rugo","year":"2019","unstructured":"Rugo HS, Finn RS, Di\u00e9ras V et al (2019) Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat 174(3):719\u2013729. https:\/\/doi.org\/10.1007\/s10549-018-05125-4","journal-title":"Breast Cancer Res Treat"},{"issue":"4","key":"9625_CR15","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S1470-2045(15)00613-0","volume":"17","author":"M Cristofanilli","year":"2016","unstructured":"Cristofanilli M, Turner NC, Bondarenko I et al (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17(4):425\u2013439. https:\/\/doi.org\/10.1016\/S1470-2045(15)00613-0","journal-title":"Lancet Oncol"},{"key":"9625_CR16","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.ejca.2022.08.012","volume":"175","author":"B Xu","year":"2022","unstructured":"Xu B, Hu X, Li W et al (2022) Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor\u2013positive\/human epidermal growth factor receptor 2\u2013negative advanced breast cancer: Primary results from PALOMA-4. Eur J Cancer 175:236\u2013245. https:\/\/doi.org\/10.1016\/j.ejca.2022.08.012","journal-title":"Eur J Cancer"},{"key":"9625_CR17","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1200\/jco.20.03639","volume":"39","author":"S Loibl","year":"2021","unstructured":"Loibl S, Marm\u00e9 F, Martin M et al (2021) Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-the penelope-B trial. J Clin Oncol 39:1518\u20131530. https:\/\/doi.org\/10.1200\/jco.20.03639","journal-title":"J Clin Oncol"},{"issue":"7","key":"9625_CR18","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1093\/annonc\/mdy155","volume":"29","author":"GN Hortobagyi","year":"2018","unstructured":"Hortobagyi GN, Stemmer SM, Burris HA et al (2018) Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 29(7):1541\u20131547. https:\/\/doi.org\/10.1093\/annonc\/mdy155","journal-title":"Ann Oncol"},{"issue":"8","key":"9625_CR19","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.annonc.2021.05.353","volume":"32","author":"DJ Slamon","year":"2021","unstructured":"Slamon DJ, Neven P, Chia S et al (2021) Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol 32(8):1015\u20131024. https:\/\/doi.org\/10.1016\/j.annonc.2021.05.353","journal-title":"Ann Oncol"},{"issue":"5","key":"9625_CR20","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1158\/1078-0432.CCR-21-3032","volume":"28","author":"YS Lu","year":"2022","unstructured":"Lu YS, Im SA, Colleoni M et al (2022) Updated overall survival of ribociclib plus endocrine therapy versus endocrine therapy alone in pre- and perimenopausal patients with HR+\/HER2- advanced breast cancer in MONALEESA-7: a phase III randomized clinical trial. Clin Cancer Res 28(5):851\u2013859. https:\/\/doi.org\/10.1158\/1078-0432.CCR-21-3032","journal-title":"Clin Cancer Res"},{"issue":"3","key":"9625_CR21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s10549-021-06334-0","volume":"189","author":"M De Laurentiis","year":"2021","unstructured":"De Laurentiis M, Borstnar S, Campone M et al (2021) Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population. Breast Cancer Res Treat 189(3):689\u2013699. https:\/\/doi.org\/10.1007\/s10549-021-06334-0","journal-title":"Breast Cancer Res Treat"},{"issue":"12","key":"9625_CR22","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1056\/nejmoa2305488","volume":"390","author":"D Slamon","year":"2024","unstructured":"Slamon D, Lipatov O, Nowecki Z et al (2024) Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med 390(12):1080\u20131091. https:\/\/doi.org\/10.1056\/nejmoa2305488","journal-title":"N Engl J Med"},{"issue":"1","key":"9625_CR23","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1001\/jamaoncol.2019.4782","volume":"6","author":"GW Sledge","year":"2020","unstructured":"Sledge GW, Toi M, Neven P et al (2020) The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy - MONARCH 2: a randomized clinical trial. JAMA Oncol 6(1):116\u2013124. https:\/\/doi.org\/10.1001\/jamaoncol.2019.4782","journal-title":"JAMA Oncol"},{"key":"9625_CR24","doi-asserted-by":"publisher","unstructured":"Johnston S, Martin M, Di Leo A, et al (2019) MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer 5(1). https:\/\/doi.org\/10.1038\/s41523-018-0097-z","DOI":"10.1038\/s41523-018-0097-z"},{"key":"9625_CR25","doi-asserted-by":"publisher","unstructured":"Zhang QY, Sun T, Yin YM et al (2020) MONARCH plus: abemaciclib plus endocrine therapy in women with HR+\/HER2\u2013 advanced breast cancer: the multinational randomized phase III study. Ther Adv Med Oncol 12.https:\/\/doi.org\/10.1177\/1758835920963925","DOI":"10.1177\/1758835920963925"},{"issue":"1","key":"9625_CR26","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1470-2045(22)00694-5","volume":"24","author":"SRD Johnston","year":"2023","unstructured":"Johnston SRD, Toi M, O\u2019Shaughnessy J et al (2023) Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol 24(1):77\u201390. https:\/\/doi.org\/10.1016\/S1470-2045(22)00694-5","journal-title":"Lancet Oncol"},{"issue":"4","key":"9625_CR27","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1093\/jnci\/djy109","volume":"111","author":"V Di\u00e9ras","year":"2019","unstructured":"Di\u00e9ras V, Rugo HS, Schnell P et al (2019) Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for HR1\/HER2- advanced breast cancer. J Natl Cancer Inst 111(4):419\u2013430. https:\/\/doi.org\/10.1093\/jnci\/djy109","journal-title":"J Natl Cancer Inst"},{"issue":"5","key":"9625_CR28","doi-asserted-by":"publisher","first-page":"e749","DOI":"10.1002\/onco.13684","volume":"26","author":"RS Finn","year":"2021","unstructured":"Finn RS, Rugo HS, Gelmon KA et al (2021) Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for hormone receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer: updated analysis with up to 5 years of follow-up. Oncologist 26(5):e749\u2013e755. https:\/\/doi.org\/10.1002\/onco.13684","journal-title":"Oncologist"},{"issue":"5","key":"9625_CR29","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41416-021-01415-9","volume":"125","author":"HA Burris","year":"2021","unstructured":"Burris HA, Chan A, Bardia A et al (2021) Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer. Br J Cancer 125(5):679\u2013686. https:\/\/doi.org\/10.1038\/s41416-021-01415-9","journal-title":"Br J Cancer"},{"issue":"1","key":"9625_CR30","doi-asserted-by":"publisher","first-page":"e53","DOI":"10.1002\/onco.13531","volume":"26","author":"HS Rugo","year":"2021","unstructured":"Rugo HS, Huober J, Garc\u00eda-S\u00e1enz JA et al (2021) Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-Negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. Oncologist 26(1):e53\u2013e65. https:\/\/doi.org\/10.1002\/onco.13531","journal-title":"Oncologist"},{"issue":"3","key":"9625_CR31","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1080\/14737140.2021.1852934","volume":"21","author":"CE Onesti","year":"2021","unstructured":"Onesti CE, Jerusalem G (2021) CDK4\/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice a systematic review and meta-analysis. Expert Rev Anticancer Ther 21(3):283\u2013298. https:\/\/doi.org\/10.1080\/14737140.2021.1852934","journal-title":"Expert Rev Anticancer Ther"},{"key":"9625_CR32","doi-asserted-by":"crossref","unstructured":"Mastrantoni L, Orlandi A, Palazzo A et al (2023) The likelihood of being helped or harmed as a patient-centred tool to assess cyclin dependent kinase 4\/6 inhibitors clinical impact and safety in metastatic breast cancer: a systematic review and sensitivity-analysis. www.thelancet.com","DOI":"10.1016\/j.eclinm.2023.101824"},{"issue":"5","key":"9625_CR33","doi-asserted-by":"publisher","first-page":"333","DOI":"10.5455\/medarh.2022.76.333-342","volume":"76","author":"D Hermansyah","year":"2022","unstructured":"Hermansyah D, Firsty NN, Alhudawy MN, Nasution RA (2022) The combination of CDK 4\/6 Inhibitors plus endocrine treatment versus endocrine treatment alone in hormone-receptor (HR)-positive breast cancer: a systematic Review and Meta-analysis. Med Arch 76(5):333\u2013342. https:\/\/doi.org\/10.5455\/medarh.2022.76.333-342","journal-title":"Med Arch"},{"key":"9625_CR34","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.2147\/CMAR.S254365","volume":"12","author":"N Xie","year":"2020","unstructured":"Xie N, Qin T, Ren W, Yao H, Yu Y, Hong H (2020) Efficacy and safety of cyclin-dependent kinases 4 and 6 inhibitors in HR+\/HER2\u2212 advanced breast cancer. Cancer Manag Res 12:4241\u20134250. https:\/\/doi.org\/10.2147\/CMAR.S254365","journal-title":"Cancer Manag Res"},{"key":"9625_CR35","doi-asserted-by":"publisher","unstructured":"Queiroz MM, Sacardo KP, Ribeiro MF et al (2023) Real-world treatment outcomes in HR+ HER2- metastatic breast cancer patients treated with CDK4\/6 inhibitors: results from a reference center in Brazil. Cancer Treat Res Commun 35. https:\/\/doi.org\/10.1016\/j.ctarc.2023.100683","DOI":"10.1016\/j.ctarc.2023.100683"},{"key":"9625_CR36","doi-asserted-by":"publisher","unstructured":"Avc\u0131 O, \u0130ria\u011fa\u00e7 Y, \u00c7avdar E, et al (2023) PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study. J Geriatr Oncol 14(8). https:\/\/doi.org\/10.1016\/j.jgo.2023.101604","DOI":"10.1016\/j.jgo.2023.101604"},{"key":"9625_CR37","doi-asserted-by":"publisher","unstructured":"KOVA\u010c ANJA, Matos E, Kuhar CG et al (2020) Efficacy and safety of selective cyclin-dependent kinases 4\/6 inhibitors in hormone-receptor-positive, HER2-negative advanced breast cancer \u2013 results from a real-world setting. Cancer Treat Res Commun 25. https:\/\/doi.org\/10.1016\/j.ctarc.2020.100201","DOI":"10.1016\/j.ctarc.2020.100201"},{"key":"9625_CR38","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1007\/s11096-023-01687-6","volume":"46","author":"T Takeda","year":"2024","unstructured":"Takeda T, Sugimoto S, Matsumoto J et al (2024) A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases. Int J Clin Pharm 46:536\u2013541. https:\/\/doi.org\/10.1007\/s11096-023-01687-6","journal-title":"Int J Clin Pharm"},{"issue":"8","key":"9625_CR39","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1177\/10781552231163121","volume":"29","author":"W Buller","year":"2023","unstructured":"Buller W, Pallan L, Chu T, Khoja L (2023) CDK4\/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset. J Oncol Pharm Pract 29(8):1825\u20131835. https:\/\/doi.org\/10.1177\/10781552231163121","journal-title":"J Oncol Pharm Pract"},{"key":"9625_CR40","doi-asserted-by":"publisher","unstructured":"Roncato R, Gerratana L, Palmero L et al (2022) An integrated pharmacological counselling approach to guide decision-making in the treatment with CDK4\/6 inhibitors for metastatic breast cancer. Front Pharmacol 13. https:\/\/doi.org\/10.3389\/fphar.2022.897951","DOI":"10.3389\/fphar.2022.897951"}],"container-title":["Supportive Care in Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-025-09625-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00520-025-09625-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-025-09625-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T04:04:44Z","timestamp":1753934684000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00520-025-09625-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,16]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["9625"],"URL":"https:\/\/doi.org\/10.1007\/s00520-025-09625-0","relation":{},"ISSN":["0941-4355","1433-7339"],"issn-type":[{"value":"0941-4355","type":"print"},{"value":"1433-7339","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,16]]},"assertion":[{"value":"17 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"588"}}