{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:55:50Z","timestamp":1790286950523,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The introduction of cyclin-dependent kinase inhibitors (CDK4\/6i) was a great advance in therapeutics for patients with estrogen receptor+\/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. Methods: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4\/6i in the period from June 2020 to June 2021. Patients &gt; 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients\u2019 epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. Results: Seventy-nine patients (median age: 62.3 years; range 39\u201383 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49\/79 patients), alopecia (25\/79), and eczematous lesions (24\/79). Cutaneous toxicities were usually mild in severity (&gt;65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. Conclusions: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4\/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients\u2019 clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers15143658","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:54:01Z","timestamp":1689728041000},"page":"3658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Cyclin-Dependent Kinase 4\/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force \u201cDermatology for Cancer Patients\u201d International Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Pietro","family":"Sollena","sequence":"first","affiliation":[{"name":"UOC Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-9152","authenticated-orcid":false,"given":"Nikolaou","family":"Vasiliki","sequence":"additional","affiliation":[{"name":"Dermato-Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, National and Kapodistrian University of Athens, 16121 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Kotteas","sequence":"additional","affiliation":[{"name":"Oncology Unit, 3rd Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, \u201cSotiria\u201d General Hospital, 16121 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Stratigos","sequence":"additional","affiliation":[{"name":"Dermato-Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, National and Kapodistrian University of Athens, 16121 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Fattore","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5253-4678","authenticated-orcid":false,"given":"Armando","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Medical Oncology, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-7951","authenticated-orcid":false,"given":"Maria","family":"Mannino","sequence":"additional","affiliation":[{"name":"Dermatologia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Di Pumpo","sequence":"additional","affiliation":[{"name":"Department of Scienza della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8026-8995","authenticated-orcid":false,"given":"Monika","family":"Fida","sequence":"additional","affiliation":[{"name":"Dermatology Service, University Hospital Center \u201cMother Theressa\u201d, 1005 Tirana, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-1527","authenticated-orcid":false,"given":"Michela","family":"Starace","sequence":"additional","affiliation":[{"name":"Dermatology\u2014IRCCS, Policlinico Sant\u2019Orsola, Department of Specialized, Experimental and Diagnostic Medicine, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Apalla","sequence":"additional","affiliation":[{"name":"Second Dermatology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Romano","sequence":"additional","affiliation":[{"name":"San Camillo Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-1863","authenticated-orcid":false,"given":"Julia","family":"Riganti","sequence":"additional","affiliation":[{"name":"Dermatology Department, Hospital Italiano de Buenos Aires, 1199 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0653-1382","authenticated-orcid":false,"given":"Sonia","family":"Segura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital del Mar\u2013Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), Universitat Aut\u00f2noma de Barcelona (UAB), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3121-5667","authenticated-orcid":false,"given":"Azael Freites","family":"Martinez","sequence":"additional","affiliation":[{"name":"Oncodermatology Clinic at Hospital Ruber Juan Bravo and Universidad Europea, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Fabbrocini","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Sibaud","sequence":"additional","affiliation":[{"name":"Oncodermatology Department, Institut Universitaire du Cancer, Toulouse Oncopole, 31500 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketty","family":"Peris","sequence":"additional","affiliation":[{"name":"UOC Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Dermatologia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the EADV Task Force \u201cDermatology for Cancer Patients\u201d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/gb4184","article-title":"Cyclin-dependent kinases","volume":"15","author":"Malumbres","year":"2014","journal-title":"Genome Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nrclinonc.2016.26","article-title":"Treating cancer with selective CDK4\/6 inhibitors","volume":"13","author":"Finn","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1470-2045(14)71159-3","article-title":"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","volume":"16","author":"Finn","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1470-2045(15)00613-0","article-title":"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","volume":"17","author":"Cristofanilli","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1056\/NEJMoa1609709","article-title":"Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer","volume":"375","author":"Hortobagyi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10549-020-06029-y","article-title":"Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer: An age-specific subgroup analysis of MONARCH 2 and 3 trials","volume":"186","author":"Goetz","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/10781552211050106","article-title":"A deep dive into CDK4\/6 inhibitors: Evaluating real world toxicities and treatment paradigms in the elderly population","volume":"29","author":"Olazagasti","year":"2021","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102086","DOI":"10.1016\/j.ctrv.2020.102086","article-title":"Comparison of treatment-related adverse events of different Cyclin-dependent kinase 4\/6 inhibitors in metastatic breast cancer: A network meta-analysis","volume":"90","author":"Desnoyers","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Raschi, E., Fusaroli, M., Ardizzoni, A., Poluzzi, E., and De Ponti, F. (2021). Thromboembolic Events with Cyclin-Dependent Kinase 4\/6 Inhibitors in the FDA Adverse Event Reporting System. Cancers, 13.","DOI":"10.3390\/cancers13081758"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1080\/14737140.2021.1852934","article-title":"CDK4\/6 inhibitors in breast cancer: Differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis","volume":"21","author":"Onesti","year":"2020","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nrc2602","article-title":"Cell cycle, CDKs and cancer: A changing paradigm","volume":"9","author":"Malumbres","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s40257-021-00645-0","article-title":"Skin Toxicities with Cyclin-Dependent Kinase 4\/6 Inhibitors in Breast Cancer: Signals from Disproportionality Analysis of the FDA Adverse Event Reporting System","volume":"23","author":"Raschi","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40264-021-01071-1","article-title":"Emerging Skin Toxicities in Patients with Breast Cancer Treated with New Cyclin-Dependent Kinase 4\/6 Inhibitors: A Systematic Review","volume":"44","author":"Silvestri","year":"2021","journal-title":"Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s10549-021-06169-9","article-title":"Cutaneous toxicities occurring during palbociclib (CDK4\/6 inhibitor) and endocrine therapy in patients with advanced breast cancer: A single-centre experience","volume":"188","author":"Chawla","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2147\/CCID.S344867","article-title":"Vitiligo-Like Lesions in a Patient with Metastatic Breast Cancer Treated with Cyclin-Dependent Kinase (CDK) 4\/6 Inhibitor: A Case Report and Literature Review","volume":"ume 15","author":"Sharaf","year":"2022","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10549-020-05914-w","article-title":"Vitiligo-like lesions in patients with advanced breast cancer treated with cycline-dependent kinases 4 and 6 inhibitors","volume":"185","author":"Sollena","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_17","unstructured":"(2020, March 19). Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/CTCAE_v5_Quick_Reference_5x7.pdf."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1080\/14737140.2017.1355242","article-title":"Fatigue, alopecia and stomatitis among patients with breast cancer re-ceiving cyclin-dependent kinase 4 and 6 inhibitors: A systematic review and meta-analysis","volume":"17","author":"Lasheen","year":"2017","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1067264","DOI":"10.3389\/fonc.2023.1067264","article-title":"Case report: Vitiligo-like toxicity due to ribociclib during first-line treatment of metastatic breast cancer: Two cases of premature interruption of therapy and exceptional response","volume":"13","author":"Pasqualoni","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40265-020-01461-2","article-title":"Inhibiting CDK4\/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences","volume":"81","author":"Braal","year":"2020","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s40257-017-0336-3","article-title":"Dermatologic Reactions to Immune Checkpoint Inhibitors: Skin Toxicities and Immunotherapy","volume":"19","author":"Sibaud","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.tcb.2018.07.002","article-title":"CDK4\/6 Inhibition in Cancer: Beyond Cell Cycle Arrest","volume":"28","author":"Goel","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature23465","article-title":"CDK4\/6 inhibition triggers anti-tumour immunity","volume":"548","author":"Goel","year":"2017","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1158\/2159-8290.CD-17-0915","article-title":"CDK4\/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation","volume":"8","author":"Deng","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1016\/j.celrep.2018.02.053","article-title":"The CDK4\/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade","volume":"22","author":"Schaer","year":"2018","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature25015","article-title":"Cyclin D\u2013CDK4 kinase destabilizes PD-L1 via cullin 3\u2013SPOP to control cancer immune surveillance","volume":"553","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ettl, T., Schulz, D., and Bauer, R.J. (2022). The Renaissance of Cyclin Dependent Kinase Inhibitors. Cancers, 14.","DOI":"10.3390\/cancers14020293"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijwd.2019.10.003","article-title":"Dermatologic conditions in women receiving systemic cancer therapy","volume":"5","author":"Ferreira","year":"2019","journal-title":"Int. J. Women\u2019s Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.ijwd.2021.07.002","article-title":"Art of prevention: The importance of dermatologic care when using aromatase inhibitors","volume":"7","author":"Behbahani","year":"2021","journal-title":"Int. J. Women\u2019s Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1634\/theoncologist.2013-0193","article-title":"Alopecia with Endocrine Therapies in Patients with Cancer","volume":"18","author":"Saggar","year":"2013","journal-title":"Oncologist"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1001\/jamadermatol.2018.0454","article-title":"Endocrine Therapy\u2013Induced Alopecia in Patients With Breast Cancer","volume":"154","author":"Shapiro","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_32","first-page":"1199","article-title":"Hair disorders in cancer survivors","volume":"80","author":"Shapiro","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jare.2016.04.001","article-title":"Aromatase inhibitors induced autoimmune disorders in patients with breast cancer: A review","volume":"7","author":"Zarkavelis","year":"2016","journal-title":"J. Adv. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-014-3150-0","article-title":"Tamoxifen-associated skin reactions in breast cancer patients: From case report to literature review","volume":"148","author":"Andrew","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/clpt.1981.154","article-title":"A method for estimating the probability of adverse drug reactions","volume":"30","author":"Naranjo","year":"1981","journal-title":"Clin. Pharmacol. Ther."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/14\/3658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:14:10Z","timestamp":1760127250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/14\/3658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,18]]},"references-count":35,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cancers15143658"],"URL":"https:\/\/doi.org\/10.3390\/cancers15143658","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,18]]}}}