{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:08Z","timestamp":1787027768840,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["WI223281"],"award-info":[{"award-number":["WI223281"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"award":["WI223281"],"award-info":[{"award-number":["WI223281"]}],"id":[{"id":"https:\/\/ror.org\/01xdqrp08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background. Ductal carcinoma in situ (DCIS) is a non-invasive disease of the breast. This study assessed the impact of the CDK4\/6 inhibitor palbociclib on halting cell cycle progression in DCIS between diagnostic biopsy and surgical resection of the lesion. Methods. A dual-arm study was conducted involving 17 participants with DCIS who were given either 100 mg of palbociclib PO daily for twelve days or no treatment before surgery. FFPE tissues from the diagnostic biopsy and from surgical specimens were analyzed to assess changes due to treatment. Results. Palbociclib treatment significantly reduced Ki67 staining in surgical tissues. RNA-seq analysis comparing the diagnostic biopsy and surgical specimens showed significant downregulation of cellular proliferation pathways after treatment. A cellular deconvolution analysis demonstrated a non-significant trend of a treatment-induced decrease in the abundance of mature luminal epithelial cells. Conclusions. Short-term palbociclib monotherapy before surgical resection was safe and well tolerated in participants. Tissue analysis showed a significant reduction in proliferation markers and the downregulation of cell cycle progression genes within DCIS. These results support further investigation of palbociclib in patients with DCIS. Trial registration. ClinicalTrials.gov NCT03535506.<\/jats:p>","DOI":"10.3390\/cancers18162630","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"2630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant Palbociclib Treatment Impacts Cell Cycle Progression of DCIS"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7331-7072","authenticated-orcid":false,"given":"Rohith","family":"Battina","sequence":"first","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace","family":"Mainor","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC 20006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-2766","authenticated-orcid":false,"given":"Marcel O.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9207-7579","authenticated-orcid":false,"given":"Gregory T.","family":"Gallanis","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-3575","authenticated-orcid":false,"given":"Ghada M.","family":"Sharif","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Walsh","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC 20006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Whitaker","sequence":"additional","affiliation":[{"name":"MedStar Georgetown Cancer Institute, Washington Hospital Center, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Greenwalt","sequence":"additional","affiliation":[{"name":"Breast Surgical Oncology, Community Health Haymarket, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy De La","family":"Cruz","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC 20006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1851-3938","authenticated-orcid":false,"given":"Nicole","family":"Swanson","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-9692","authenticated-orcid":false,"given":"Kerrie B.","family":"Bouker","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-4950","authenticated-orcid":false,"given":"Anton","family":"Wellstein","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-5162","authenticated-orcid":false,"given":"Paula R.","family":"Pohlmann","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-8612","authenticated-orcid":false,"given":"Anna T.","family":"Riegel","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","unstructured":"Tomlinson-Hansen, S.E., Khan, M., and Cassaro, S. (2025, December 04). Breast Ductal Carcinoma in Situ, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK567766\/."},{"key":"ref_2","first-page":"477","article-title":"Breast cancer statistics 2024","volume":"74","author":"Giaquinto","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s10549-005-9101-z","article-title":"The natural history of ductal carcinoma in situ of the breast: A review","volume":"97","author":"Erbas","year":"2006","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Consensus Conference Committee (1997). Consensus conference on the classification of ductal carcinoma in Situ. Cancer, 80, 1798\u20131802.","DOI":"10.1002\/(SICI)1097-0142(19971101)80:9<1798::AID-CNCR15>3.0.CO;2-0"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.5858\/133.1.15","article-title":"Protocol for the Examination of Specimens From Patients With Ductal Carcinoma In Situ of the Breast","volume":"133","author":"Lester","year":"2009","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/his.14091","article-title":"The 2019 World Health Organization classification of tumours of the breast","volume":"77","author":"Tan","year":"2020","journal-title":"Histopathology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41416-019-0478-6","article-title":"Ductal carcinoma in situ: To treat or not to treat, that is the question","volume":"121","author":"Lips","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e305","DOI":"10.1016\/j.ijrobp.2011.12.092","article-title":"Long-term outcome in patients with ductal carcinoma in situ treated with breast-conserving therapy: Implications for optimal follow-up strategies","volume":"83","author":"Shaitelman","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1748-717X-7-177","article-title":"Conservative treatment of breast ductal carcinoma in situ: Results of an Italian multi-institutional retrospective study","volume":"7","author":"Vidali","year":"2012","journal-title":"Radiat. Oncol. Lond. Engl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1634\/theoncologist.12-11-1276","article-title":"Current treatment and clinical trial developments for ductal carcinoma in situ of the breast","volume":"12","author":"Boughey","year":"2007","journal-title":"Oncologist"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/jnci\/djr027","article-title":"Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS","volume":"103","author":"Wapnir","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1001\/jamaoncol.2015.2510","article-title":"Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ","volume":"1","author":"Narod","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1056\/NEJMoa1103507","article-title":"Exemestane for Breast-Cancer Prevention in Postmenopausal Women","volume":"364","author":"Goss","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/jncimonographs\/lgq021","article-title":"The Impact of Systemic Therapy Following Ductal Carcinoma In Situ","volume":"2010","author":"Costantino","year":"2010","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0140-6736(19)32955-1","article-title":"Use of anastrozole for breast cancer prevention (IBIS-II): Long-term results of a randomised controlled trial","volume":"395","author":"Cuzick","year":"2020","journal-title":"Lancet Lond. Engl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10549-018-4681-6","article-title":"Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: A study based on nationwide Korean Breast Cancer Registry database","volume":"169","author":"Hwang","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1505270","article-title":"Palbociclib in Hormone-Receptor\u2013Positive Advanced Breast Cancer","volume":"373","author":"Turner","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s10549-020-05755-7","article-title":"Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+\/HER2\u2212 advanced breast cancer (PALOMA-1, TRIO-18)","volume":"183","author":"Finn","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1158\/1535-7163.1427.3.11","article-title":"Specific inhibition of cyclin-dependent kinase 4\/6 by PD 0332991 and associated antitumor activity in human tumor xenografts","volume":"3","author":"Fry","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1158\/1078-0432.CCR-11-0509","article-title":"Phase I, Dose-Escalation Trial of the Oral Cyclin-Dependent Kinase 4\/6 Inhibitor PD 0332991, Administered Using a 21-Day Schedule in Patients with Advanced Cancer","volume":"18","author":"Flaherty","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1186\/bcr2419","article-title":"PD 0332991, a selective cyclin D kinase 4\/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro","volume":"11","author":"Finn","year":"2009","journal-title":"Breast Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1158\/1535-7163.MCT-19-0231","article-title":"Short and long-term effects of CDK4\/6 inhibition on early stage breast cancer","volume":"18","author":"Kietzman","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular signatures database (MSigDB) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"Newman","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tabula Sapiens Consortium*, Jones, R.C., Karkanias, J., Krasnow, M.A., Pisco, A.O., Quake, S.R., Salzman, J., Yosef, N., Bulthaup, B., and Brown, P. (2022). The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans. Science, 376, eabl4896.","DOI":"10.1126\/science.abl4896"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1158\/1078-0432.CCR-19-4191","article-title":"Activation of the interferon signaling pathway is associated with resistance to CDK4\/6 inhibitors and immune checkpoint activation in ER-positive breast cancer","volume":"27","author":"Fu","year":"2021","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1200\/JCO.21.02554","article-title":"Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42\/AFT-05\/BIG-14-03)","volume":"40","author":"Gnant","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1200\/JCO.18.01624","article-title":"Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial","volume":"37","author":"Johnston","year":"2019","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1200\/JCO.2001.19.8.2263","article-title":"Risk Factors for Recurrence and Metastasis After Breast-Conserving Therapy for Ductal Carcinoma-In-Situ: Analysis of European Organization for Research and Treatment of Cancer Trial 10853","volume":"19","author":"Bijker","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/jnci\/djk020","article-title":"Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer","volume":"99","author":"Dowsett","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"P2-03-29","DOI":"10.1158\/1557-3265.SABCS24-P2-03-29","article-title":"Abstract P2-03-29: Upregulation of senescence signatures and interferon-signalling after short-term pre-operative CDK4\/6 inhibitor\u2014Gene expression analysis from the POP and ABC-POP trials","volume":"31","author":"Job","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gallanis, G.T., Sharif, G.M., Schmidt, M.O., Friedland, B.N., Battina, R., Rahhal, R., Davis, J.E., Khan, E.S., Wellstein, A., and Riegel, A.T. (2023). Stromal Senescence following Treatment with the CDK4\/6 Inhibitor Palbociclib Alters the Lung Metastatic Niche and Increases Metastasis of Drug-Resistant Mammary Cancer Cells. Cancers, 15.","DOI":"10.3390\/cancers15061908"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2630\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:17:14Z","timestamp":1786961834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":35,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162630"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162630","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}