Yu Q, Sicinska E, Geng Y, Ahnström M, Zagozdzon A, Kong Y, Gardner H, Kiyokawa H, Harris LN, Stål O, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9(1):23–32.
Choi YJ, Li X, Hydbring P, Sanda T, Stefano J, Christie AL, Signoretti S, Look AT, Kung AL, von Boehmer H, et al. The requirement for cyclin D function in tumor maintenance. Cancer Cell. 2012;22(4):438–51.
O’Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 2016;13(7):417–30.
Hamilton E, Infante JR. Targeting CDK4/6 in patients with cancer. Cancer Treat Rev. 2016;45:129–38.
Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, et al. 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. 2015;16(1):25–35.
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.
Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(25):2875–84.
Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307–16.
Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–36.
Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.
Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379(20):1926–36.
Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, et al. 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. 2016;17(4):425–39.
Turner NC, Liu Y, Zhu Z, Loi S, Colleoni M, Loibl S, DeMichele A, Harbeck N, André F, Bayar MA, et al. Cyclin E1 expression and palbociclib efficacy in previously treated hormone receptor-positive metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(14):1169–78.
Finn RS, Liu Y, Zhu Z, Martin M, Rugo HS, Diéras V, Im SA, Gelmon KA, Harbeck N, Lu DR, et al. Biomarker analyses of response to cyclin-dependent kinase 4/6 inhibition and endocrine therapy in women with treatment-naïve metastatic breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2020;26(1):110–21.
Sherr CJ, Beach D, Shapiro GI. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 2016;6(4):353–67.
Klein ME, Kovatcheva M, Davis LE, Tap WD, Koff A. CDK4/6 inhibitors: the mechanism of action may not be as simple as once thought. Cancer Cell. 2018;34(1):9–20.
Scheicher R, Hoelbl-Kovacic A, Bellutti F, Tigan AS, Prchal-Murphy M, Heller G, Schneckenleithner C, Salazar-Roa M, Zochbauer-Muller S, Zuber J, et al. CDK6 as a key regulator of hematopoietic and leukemic stem cell activation. Blood. 2015;125(1):90–101.
Hu MG, Deshpande A, Schlichting N, Hinds EA, Mao C, Dose M, Hu GF, Van Etten RA, Gounari F, Hinds PW. CDK6 kinase activity is required for thymocyte development. Blood. 2011;117(23):6120–31.
Min IM, Pietramaggiori G, Kim FS, Passegué E, Stevenson KE, Wagers AJ. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell. 2008;2(4):380–91.
Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.
Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 2018;8(2):216–33.
Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017;548(7668):471–5.
Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69(13):5383–91.
Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X. Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw JNCCN. 2015;13(10):1225–31.
Trédan O, Manuel M, Clapisson G, Bachelot T, Chabaud S, Bardin-dit-Courageot C, Rigal C, Biota C, Bajard A, Pasqual N, et al. Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome. Eur J Cancer (Oxford, England, 1990). 2013;49(7):1673–82.
Donskov F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol. 2013;23(3):200–7.
Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol. 2018;19(2):108–19.
Gabrilovich DI. Myeloid-derived suppressor cells. Cancer Immunol Res. 2017;5(1):3–8.
Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res BCR. 2017;19(1):2.
Desnoyers A, Nadler MB, Kumar V, Saleh R, Amir E. Comparison of treatment-related adverse events of different Cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer: a network meta-analysis. Cancer Treat Rev. 2020;90:102086.
Kim CG, Sim NS, Kim JE, Yun KH, Lee YH, Kim SH, Baek W, Han YD, Kim SK, Kim JH, et al. Phase II clinical trial of eribulin-gemcitabine combination therapy in previously treated patients with advanced liposarcoma or leiomyosarcoma. Clin Cancer Res. 2022;28(15):3225–34.
Kim CG, Jang M, Kim Y, Leem G, Kim KH, Lee H, Kim TS, Choi SJ, Kim HD, Han JW, et al. VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers. Sci Immunol. 2019;4(41):1.
Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, et al. Defining “T cell exhaustion.” Nat Rev Immunol. 2019;19(11):665–74.
Kim CG, Hong MH, Kim KH, Seo IH, Ahn BC, Pyo KH, Synn CB, Yoon HI, Shim HS, Lee YI, et al. Dynamic changes in circulating PD-1(+)CD8(+) T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer. Eur J Cancer (Oxford, England, 1990). 1990;2020(143):113–26.
Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150.
Diéras V, Harbeck N, Joy AA, Gelmon K, Ettl J, Verma S, Lu DR, Gauthier E, Schnell P, Mori A, et al. Palbociclib with letrozole in postmenopausal women with ER+/HER2− advanced breast cancer: hematologic safety analysis of the randomized PALOMA-2 trial. Oncologist. 2019;24(12):1514–25.
Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D, Ponce S, Ares LP, Leroy L, Audigier-Valette C, et al. Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer. JAMA Oncol. 2018;4(3):351–7.
Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko SS, Han W. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(17):2360–8.
Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, Werner MT, Huang AC, Alexander KA, Wu JE, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571(7764):211–8.
Teh JLF, Aplin AE. Arrested developments: CDK4/6 inhibitor resistance and alterations in the tumor immune microenvironment. Clin Cancer Res Off J Am Assoc Cancer Res. 2019;25(3):921–7.
Turner NC, Finn RS, Martin M, Im SA, DeMichele A, Ettl J, Diéras V, Moulder S, Lipatov O, Colleoni M, et al. Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases. Ann Oncol Off J Eur Soc Med Oncol. 2018;29(3):669–80.
Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, et al. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discov. 2020;10(8):1174–93.
O’Leary B, Cutts RJ, Liu Y, Hrebien S, Huang X, Fenwick K, Andre F, Loibl S, Loi S, Garcia-Murillas I, et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 2018;8(11):1390–403.
Verma R, Foster RE, Horgan K, Mounsey K, Nixon H, Smalle N, Hughes TA, Carter CR. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Breast Cancer Res. 2016;18(1):10.
Zattarin E, Fabbroni C, Ligorio F, Nichetti F, Lobefaro R, et al. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of CDK 4/6 inhibitors in women with hormone receptor-positive/HER2-negative advanced breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2020;31:S15–41.
Park JH, Jonas SF, Bataillon G, Criscitiello C, Salgado R, Loi S, Viale G, Lee HJ, Dieci MV, Kim SB, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol Off J Eur Soc Med Oncol. 2019;30(12):1941–9.
Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674–90.
Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 2015;1(4):448–54.
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.
Stanton SE, Adams S, Disis ML. Variation in the Incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA Oncol. 2016;2(10):1354–60.
Dieci MV, Griguolo G, Miglietta F, Guarneri V. The immune system and hormone-receptor positive breast cancer: Is it really a dead end? Cancer Treat Rev. 2016;46:9–19.
CDK4/6 Inhibitors Induce Antitumor Immunity. Cancer discovery. 2017; 7(10):1052.
Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, Tan Y, Ci Y, Wu F, Dai X, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553(7686):91–5.
Kim SY, Kim SM, Lim S, Lee JY, Choi SJ, Yang SD, Yun MR, Kim CG, Gu SR, Park C, et al. Modeling clinical responses to targeted therapies by patient-derived organoids of advanced lung adenocarcinoma. Clin Cancer Res. 2021;27(15):4397–409.
Ham A, Kim MH, Kim GM, Kim JH, Kim JY, Park HS, Park S, Cho YU, Park BW, Kim SI, et al. Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer. Breast Cancer Res Treat. 2020;183(1):107–16.