Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.

Article  PubMed  Google Scholar 

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49.

Article  PubMed  Google Scholar 

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5(1):66–66.

Article  PubMed  Google Scholar 

Gnant M, Turner NC, Hernando C. Managing a long and winding road: estrogen receptor-positive breast cancer. In: American Society of Clinical Oncology educational book American Society of Clinical Oncology Annual Meeting. 2023;43:e390922–e390922.

Google Scholar 

Hamilton E, Infante JR. Targeting CDK4/6 in patients with cancer. Cancer Treat Rev. 2016;45:129–38.

Article  CAS  PubMed  Google Scholar 

Steger GG, Gnant M, Bartsch R. Palbociclib for the treatment of postmenopausal breast cancer - an update. Expert Opin Pharmacother. 2016;17(2):255–63.

Article  CAS  PubMed  Google Scholar 

Iwata H. Clinical development of CDK4/6 inhibitor for breast cancer. Breast Cancer. 2018;25(4):402–6.

Article  PubMed  Google Scholar 

Hanahan D, Weinberg RA. The Hallmarks of Cancer. Cell. 2000;100(1):57–70.

Article  CAS  PubMed  Google Scholar 

Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144(5):646–74.

Article  CAS  PubMed  Google Scholar 

Hartwell LH, Kastan MB. Cell cycle control and cancer. Science. 1994;266(5192):1821–8.

Article  CAS  PubMed  Google Scholar 

Talluri S, Dick FA. Regulation of transcription and chromatin structure by pRB. Cell Cycle. 2012;11(17):3189–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Witkiewicz AK, Knudsen ES. Retinoblastoma tumor suppressor pathway in breast cancer: prognosis, precision medicine, and therapeutic interventions. Breast Cancer Res. 2014;16(2):207.

Article  PubMed  PubMed Central  Google Scholar 

Np P. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. Journal of molecular biology. 1999;287(5).

Weintraub SJ, Prater CA, Dean DC. Retinoblastoma protein switches the E2F site from positive to negative element. Nature. 1992;358(6383):259–61.

Article  CAS  PubMed  Google Scholar 

Sw H, Sp C, Jm H, Jr N. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992;6(2):177–85.

Ewen ME, Sluss HK, Whitehouse LL, Livingston DM. TGF beta inhibition of Cdk4 synthesis is linked to cell cycle arrest. Cell. 1993;74(6):1009–20.

Article  CAS  PubMed  Google Scholar 

Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6 inhibitor in various solid tumors. Clin Cancer Res. 2017;23(13):3251–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501–12.

Article  CAS  PubMed  Google Scholar 

Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75(4):805–16.

Article  CAS  PubMed  Google Scholar 

Blain SW, Montalvo E, Massagué J. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4. J Biol Chem. 1997;272(41):25863–72.

Article  CAS  PubMed  Google Scholar 

LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, et al. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997;11(7):847–62.

Article  CAS  PubMed  Google Scholar 

Robinson TJW, Liu JC, Vizeacoumar F, Sun T, Maclean N, Egan SE, et al. RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs. PLoS ONE. 2013;8(11): e78641.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.

Article  PubMed  Google Scholar 

Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Science Signaling. 2013;6(269):pl1.

Article  PubMed  PubMed Central  Google Scholar 

Sabbah M, Courilleau D, Mester J, Redeuilh G. Estrogen induction of the cyclin D1 promoter: Involvement of a cAMP response-like element. Proc Natl Acad Sci U S A. 1999;96(20):11217–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zwijsen RM, Wientjens E, Klompmaker R, van der Sman J, Bernards R, Michalides RJ. CDK-independent activation of estrogen receptor by cyclin D1. Cell. 1997;88(3):405–15.

Article  CAS  PubMed  Google Scholar 

Rugo HS, Kabos P, Beck JT, Jerusalem G, Wildiers H, Sevillano E, et al. Abemaciclib in combination with pembrolizumab for HR+, HER2− metastatic breast cancer: phase 1b study. NPJ Breast Cancer. 2022;8(1):118.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mayer EL, Ren Y, Wagle N, Mahtani R, Ma C, DeMichele A, et al. PACE: a randomized phase II study of fulvestrant, palbociclib, and avelumab after progression on cyclin-dependent kinase 4/6 inhibitor and aromatase inhibitor for hormone receptor–positive/human epidermal growth factor receptor-negative metastatic breast cancer. JCO. 2024;42(17):2050–60.

Article  CAS  Google Scholar 

Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017;548(7668):471–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schaer DA, Beckmann RP, Dempsey JA, Huber L, Forest A, Amaladas N, et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Rep. 2018;22(11):2978–94.

Chaikovsky AC, Sage J. Beyond the cell cycle: enhancing the immune surveillance of tumors via CDK4/6 inhibition. Mol Cancer Res. 2018;16(10):1454–7.

Heckler M, Ali LR, Clancy-Thompson E, Qiang L, Ventre KS, Lenehan P, et al. Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation. Cancer Discov. 2021;11(10):2564–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuan Y, Lee JS, Yost SE, Frankel PH, Ruel C, Egelston CA, et al. Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur J Cancer. 2021;154:11–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Masuda J, Sakai H, Tsurutani J, Tanabe Y, Masuda N, Iwasa T, et al. Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2−negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial). J Immunother Cancer. 2023;11(9): e007126.

Article  PubMed  PubMed Central  Google Scholar 

Jerusalem G, Prat A, Salgado R, Reinisch M, Saura C, Ruiz-Borrego M, et al. Neoadjuvant nivolumab + palbociclib + anastrozole for oestrogen receptor-positive/human epidermal growth factor receptor 2-negative primary breast cancer: Results from CheckMate 7A8. The Breast. 2023;72:103580.

Herold CI, Trippa L, Li T, Do K, B