Therapy for Hormone Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer Following Treatment Progression via CDK4/6 Inhibitors: A Literature Review

References

• Sung H, Ferlay J, Siegel RL, 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):209–249. doi:10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Anderson WF, Chatterjee N, Ershler WB, et al. Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database. Breast Cancer Res Treat. 2002;76(1):27–36. doi:10.1023/A:1020299707510
   PubMed Web of Science ®Google Scholar
• Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975–2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 2015;107(6):djv048. doi:10.1093/jnci/djv048
   PubMed Web of Science ®Google Scholar
• Flaum LE, Gradishar WJ. Advances in endocrine therapy for postmenopausal metastatic breast cancer. Cancer Treat Res. 2018;173:141–154.
   PubMedGoogle Scholar
• Hoffmann J, Bohlmann R, Heinrich N, et al. Characterization of new estrogen receptor destabilizing compounds: effects on estrogen-sensitive and tamoxifen-resistant breast cancer. J Natl Cancer Inst. 2004;96:210–218. doi:10.1093/jnci/djh022
   PubMed Web of Science ®Google Scholar
• Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–1936. doi:10.1056/NEJMoa1607303
   PubMed Web of Science ®Google Scholar
• Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–1748. doi:10.1056/NEJMoa1609709
   PubMed Web of Science ®Google Scholar
• Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638–3646. doi:10.1200/JCO.2017.75.6155
   PubMed Web of Science ®Google Scholar
• Gw S Jr, Toi M, Neven P, 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. 2017;35:2875–2884. doi:10.1200/JCO.2017.73.7585
   PubMed Web of Science ®Google Scholar
• Cristofanilli M, Turner NC, Bondarenko I, 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):425–439. doi:10.1016/S1470-2045(15)00613-0
   PubMed Web of Science ®Google Scholar
• Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36:2465–2472. doi:10.1200/JCO.2018.78.9909
   PubMed Web of Science ®Google Scholar
• Konecny GE, Winterhoff B, Kolarova T, et al. Expression of p16 and retinoblastoma determines response to CDK 4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011;17:1591–1602. doi:10.1158/1078-0432.CCR-10-2307
   PubMed Web of Science ®Google Scholar
• Herrera-Abreu MT, Palafox M, Asghar U, et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer. Cancer Res. 2016;76:2301–2313. doi:10.1158/0008-5472.CAN-15-0728
   PubMed Web of Science ®Google Scholar
• Malorni L, Piazza S, Ciani Y, et al. A gene expression signature of retinoblastoma loss-of function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer. Oncotarget. 2016;7:68012–68022. doi:10.18632/oncotarget.12010
   PubMed Web of Science ®Google Scholar
• Taylor-Harding B, Aspuria PJ, Agadjanian H, et al. Cyclin E1 and RTK/RAS signaling drive CDK inhibitor resistance via activation of E2F and ETS. Oncotarget. 2015;6:696–714. doi:10.18632/oncotarget.2673
   PubMed Web of Science ®Google Scholar
• Yang C, Li Z, Bhatt T, et al. Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene. 2017;36:2255–2264. doi:10.1038/onc.2016.379
   PubMed Web of Science ®Google Scholar
• Franco J, Witkiewicz AK, Knudsen ES. CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer. Oncotarget. 2014;5:6512–6525. doi:10.18632/oncotarget.2270
   PubMed Web of Science ®Google Scholar
• Dean J, Thangavel C, McClendon AK, et al. Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. Oncogene. 2010;29(28):4018–4032. doi:10.1038/onc.2010.154
   PubMed Web of Science ®Google Scholar
• Cen L, Carlson BL, Schroeder MA, et al. p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 2012;14(7):870–881. doi:10.1093/neuonc/nos114
   PubMed Web of Science ®Google Scholar
• Wu A, Wu B, Guo J, et al. Elevated expression of CDK4 in lung cancer. J Transl Med. 2011;9(1):38. doi:10.1186/1479-5876-9-38
   PubMedGoogle Scholar
• Olanich ME, Sun W, Hewitt SM, et al. CDK4 amplification reduces sensitivity to CDK4/6 inhibition in fusion-positive rhabdomyosarcoma. Clin Cancer Res. 2015;21(21):4947–4959. doi:10.1158/1078-0432.CCR-14-2955
   PubMed Web of Science ®Google Scholar
• Matheson CJ, Backos DS, Philip Reigan P. Targeting WEE1 kinase in cancer. Trends Pharmacol Sci. 2016;37:872–881. doi:10.1016/j.tips.2016.06.006
   PubMed Web of Science ®Google Scholar
• Wander SA, Cohen O, Gong X, 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;10:1174–1193. doi:10.1158/2159-8290.CD-19-1390
   PubMed Web of Science ®Google Scholar
• Fujita T, Liu W, Doihara H, et al. Regulation of Skp2-p27 axis by the Cdh1/anaphase-promoting complex pathway in colorectal tumorigenesis. Am J Pathol. 2008;173(1):217–228. doi:10.2353/ajpath.2008.070957
   PubMed Web of Science ®Google Scholar
• Li Z, Razavi P, Li Q, et al. Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the hippo pathway. Cancer Cell. 2018;34(6):893–905. doi:10.1016/j.ccell.2018.11.006
   PubMed Web of Science ®Google Scholar
• Li Q, Jiang B, Guo J, et al. INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors. Cancer Discov. 2022;12(2):356–371. doi:10.1158/2159-8290.CD-20-1726
   PubMed Web of Science ®Google Scholar
• Jansen VM, Bhola NE, Bauer JA, et al. Kinome-Wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer. Cancer Res. 2017;77(9):2488–2499. doi:10.1158/0008-5472.CAN-16-2653
   PubMed Web of Science ®Google Scholar
• Zelivianski S, Cooley A, Kall R, et al. CDK4-mediated phosphorylation inhibits Smad3 activity in cyclin D overexpressing breast cancer cells. Mol Cancer Res. 2010;8(10):1375–1387. doi:10.1158/1541-7786.MCR-09-0537
   PubMed Web of Science ®Google Scholar
• Vijayaraghavan S, Karakas C, Doostan I, et al. CDK4/6 and autophagy inhibitors induce senescence in Rb positive cytoplasmic cyclin E negative synergisticallycancers. Nat Commun. 2017;8:15916. doi:10.1038/ncomms15916
   PubMed Web of Science ®Google Scholar
• Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol. 2018;29(8):1634–1657. doi:10.1093/annonc/mdy192
   PubMed Web of Science ®Google Scholar
• Boér K. Fulvestrant in advanced breast cancer: evidence to date and place in therapy. Ther Adv Med Oncol. 2017;9(7):465–479. doi:10.1177/1758834017711097
   PubMed Web of Science ®Google Scholar
• Hu X, Li T, Wang B, et al. Comparison of 4th ESO-ESMO international consensus guidelines for advance breast cancer and Chinese anti-cancer association committee of Breast Cancer Society guideline. Breast. 2019;45:36–42. doi:10.1016/j.breast.2019.02.009
   PubMed Web of Science ®Google Scholar
• Martin JM, Handorf EA, Montero AJ, et al. Systemic Therapies following progression on first-line CDK4/6-inhibitor treatment: analysis of real-world data. Oncologist. 2022;27(6):441–446. doi:10.1093/oncolo/oyac075
   PubMed Web of Science ®Google Scholar
• Samuel Eziokwu A, Varella L, Lynn Kruse M, et al. Real-world outcomes of cyclin-dependent kinase inhibitors continued beyond first disease progression in hormone receptor-positive metastatic breast cancer. Clin Breast Cancer. 2021;21(3):205–209. doi:10.1016/j.clbc.2020.09.010
   PubMed Web of Science ®Google Scholar
• Wander SA, Han HS, Zangardi ML, et al. Clinical outcomes with abemaciclib after prior CDK4/6 inhibitor progression in breast cancer: a multicenter experience. J Natl Compr Canc Netw. 2021:1–8. doi:10.6004/jnccn.2020.7662
   PubMedGoogle Scholar
• Kalinsky K, Accordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin- dependent kinase 4/6 inhibition (CDK4/6i) in patients(pts) with unresectable or hormone receptor-positive (HR+), HER2-negative metastatic breast cancer(MBC):MAINTAIN trial. J Clin Oncol. 2022;40(17):LBA1004.
   Web of Science ®Google Scholar
• L ME, Ren Y, Wagle N, et al. GS3-06 palbociclib after CDK4/6i and endocrine therapy (PACE): a randomized phase II study of fulvestrant, palbociclib, and avelumab for endocrine pre-treated er+/HER2- metastatic breast cancer. In: San Antonio Breast Cancer Symposium; San Antonio, Texas; 2022.
   Google Scholar
• Albanell J, M P-GJ, Gil-Gil M, et al. Palbociclib rechallenge for hormone receptor- positive/HER-negative advanced breast cancer: findings from the phase II BioPER trial. Clin Cancer Res. 2023;29:1):67–80. doi:10.1158/1078-0432.CCR-22-1281
   Web of Science ®Google Scholar
• Bardia A, Hurvitz SA, DeMichele A, et al. Phase I/II trial of exemestane, ribociclib, and everolimus in women with HR +/HER2 - advanced breast cancer after progression on CDK4/6 inhibitors (TRINITI-1). Clin Cancer Res. 2021;27(15):4177–4185. doi:10.1158/1078-0432.CCR-20-2114
   PubMed Web of Science ®Google Scholar
• Mayer IA, Abramson VG, Formisano L, et al. A phase Ib study of alpelisib (BYL719), a PI3Kα- specific inhibitor, with letrozole in ER+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23(1):26–34. doi:10.1158/1078-0432.CCR-16-0134
   PubMed Web of Science ®Google Scholar
• Juric D, Janku F, Rodón J, et al. Alpelisib plus fulvestrant in PIK3CA-altered and PIK3CA- wild type estrogen receptor-positive advanced breast cancer: a phase 1b clinical trial. JAMA Oncol. 2019;5(2):e184475. doi:10.1001/jamaoncol.2018.4475
   PubMed Web of Science ®Google Scholar
• André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor- positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–1940. doi:10.1056/NEJMoa1813904
   PubMed Web of Science ®Google Scholar
• Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a Phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22(4):489–498. doi:10.1016/S1470-2045(21)00034-6
   PubMed Web of Science ®Google Scholar
• Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor- positive advanced breast cancer. N Engl J Med. 2012;366(6):520–529. doi:10.1056/NEJMoa1109653
   PubMed Web of Science ®Google Scholar
• Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in Postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–884. doi:10.1007/s12325-013-0060-1
   PubMed Web of Science ®Google Scholar
• Cook MM, Al Rabadi L, Kaempf AJ, et al. Everolimus plus exemestane treatment in metastatic hormone receptor-positive breast cancer patients previously treated with CDK4/6 inhibitor therapy. Oncologist. 2021;26(2):101–106. doi:10.1002/onco.13609
   PubMed Web of Science ®Google Scholar
• Mo H, Renna CE, Moore HCF, et al. Real-world outcomes of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors. Clin Breast Cancer. 2022;22(2):143–148. doi:10.1016/j.clbc.2021.10.002
   PubMed Web of Science ®Google Scholar
• Smyth LM, Batist G, Meric-Bernstam F, et al. Selective AKT kinase inhibitor capivasertib in combination with fulvestrant inPTEN-mutant ER-positive metastatic breast cancer. NPJ Breast Cancer. 2021;7(1):44. doi:10.1038/s41523-021-00251-7
   PubMed Web of Science ®Google Scholar
• Jones RH, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21(3):345–357. doi:10.1016/S1470-2045(19)30817-4
   PubMed Web of Science ®Google Scholar
• Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor- positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022;23(7):851–864. doi:10.1016/S1470-2045(22)00284-4
   PubMed Web of Science ®Google Scholar
• Turner N, Oliveira M, J HS, et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058–2070. doi:10.1056/NEJMoa2214131
   PubMed Web of Science ®Google Scholar
• Beck A, Goetsch L, Dumontet C, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315–337. doi:10.1038/nrd.2016.268
   PubMed Web of Science ®Google Scholar
• Ambrogi F, Fornili M, Boracchi P, et al. Trop-2 is a determinant of breast cancer survival. PLoS One. 2014;9(5):e96993. doi:10.1371/journal.pone.0096993
   PubMed Web of Science ®Google Scholar
• Trerotola M, Cantanelli P, Guerra E, et al. Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. 2013;32(2):222–233. doi:10.1038/onc.2012.36
   PubMed Web of Science ®Google Scholar
• Goldenberg DM, Sharkey RM. Sacituzumab govitecan, a novel, third-generation, antibody- drug conjugate (ADC) for cancer therapy. Expert Opin Biol Ther. 2020;20(8):871–885. doi:10.1080/14712598.2020.1757067
   PubMed Web of Science ®Google Scholar
• Nagayama A, Vidula N, Ellisen L, et al. Novel antibody-drug conjugates for triple negative breast cancer. Ther Adv Med Oncol. 2020;12:1758835920915980. doi:10.1177/1758835920915980
   Web of Science ®Google Scholar
• Goldenberg DM, Cardillo TM, Govindan SV, et al. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015;6(26):22496–22512. doi:10.18632/oncotarget.4318
   PubMedGoogle Scholar
• Cardillo TM, Govindan SV, Sharkey RM, et al. Sacituzumab govitecan (IMMU-132), an anti- trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug Chem. 2015;26(5):919–931. doi:10.1021/acs.bioconjchem.5b00223
   PubMed Web of Science ®Google Scholar
• Govindan SV, Cardillo TM, Sharkey RM, et al. Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers. Mol Cancer Ther. 2013;12(6):968–978. doi:10.1158/1535-7163.MCT-12-1170
   PubMed Web of Science ®Google Scholar
• Rugo HS, Bardia A, Marmé F, et al. Sacituzumab govitecan in hormone receptor- positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365–3376. doi:10.1200/JCO.22.01002
   PubMed Web of Science ®Google Scholar
• Modi S, Park H, Murthy RK, et al. Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low expressing advanced breast cancer: results from a phase Ib study. J Clin Oncol. 2020;38(17):1887–1896. doi:10.1200/JCO.19.02318
   PubMed Web of Science ®Google Scholar
• Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2- low advanced breast cancer trial investigators. N Engl J Med. 2022;387(1):9–20. doi:10.1056/NEJMoa2203690
   PubMed Web of Science ®Google Scholar
• Turner NC, Swift C, Kilburn L, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor-positive breast cancer: a combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res. 2020;26(19):5172–5177. doi:10.1158/1078-0432.CCR-20-0224
   PubMed Web of Science ®Google Scholar
• Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388(10063):2997–3005. doi:10.1016/S0140-6736(16)32389-3
   PubMed Web of Science ®Google Scholar
• Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD Trial. J Clin Oncol. 2022;40(28):3246–3256. doi:10.1200/JCO.22.00338
   PubMed Web of Science ®Google Scholar
• Oliveira M, Pominchuck D, Nowecki Z, et al. GS3-02 Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2- negative breast cancer: results of the randomized, multi-dose Phase 2 SERENA-2 trial. San Antonio Breast Cancer Symposium; San Antonio, Texas; 2022.
   Google Scholar
• Tolaney SM, Chan A, Petrakova K, et al. AMEERA-3: randomized Phase II study of amcenestrant (oral selective estrogen receptor degrader) versus standard endocrine monotherapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol. 2023;41(24):4014–4024. doi:10.1200/JCO.22.02746
   PubMed Web of Science ®Google Scholar
• Martin Jimenez M, Lim E, Chavez Mac Gregor M, et al. 211MO Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2-locally advanced/metastatic breast cancer (LA/mBC): primary analysis of the phase II, randomised, open-label acelERA BC study. Ann Oncol. 2022;33:S633–S634. doi:10.1016/j.annonc.2022.07.250
   Google Scholar
• Robert NJ, Vogel CL, Henderson IC, et al. The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer. Semin Oncol. 2004;31(6 Suppl 13):106–146. doi:10.1053/j.seminoncol.2004.09.018
   PubMed Web of Science ®Google Scholar
• Mauri D, Kamposioras K, Tsali L, et al. Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: a meta-analysis. Cancer Treat Rev. 2010;36(1):69–74. doi:10.1016/j.ctrv.2009.10.006
   PubMed Web of Science ®Google Scholar
• Petrelli F, Di Cosimo S, Lonati V, et al. Vinorelbine with capecitabine, an evergreen doublet for advanced breast cancer: a systematic literature review and pooled-analysis of Phase II-III studies. Clin Breast Cancer. 2016;16(5):327–334. doi:10.1016/j.clbc.2016.05.002
   PubMed Web of Science ®Google Scholar
• Kaufman PA, Awada A, Twelves C, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33(6):594–601. doi:10.1200/JCO.2013.52.4892
   PubMed Web of Science ®Google Scholar
• Zhang P, Sun T, Zhang Q, et al. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol. 2017;18(3):371–383. doi:10.1016/S1470-2045(17)30088-8
   PubMed Web of Science ®Google Scholar
• Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–533. doi:10.1056/NEJMoa1706450
   PubMed Web of Science ®Google Scholar
• Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753–763. doi:10.1056/NEJMoa1802905
   PubMed Web of Science ®Google Scholar
• Tung NM, Robson ME, Ventz S, et al. TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020;38(36):4274–4282. doi:10.1200/JCO.20.02151
   PubMed Web of Science ®Google Scholar
• Doostan I, Karakas C, Kohansal M, et al. Cytoplasmic cyclin E mediates resistance to aromatase inhibitors in breast cancer. Clin Cancer Res. 2017;23(23):72887300. doi:10.1158/1078-0432.CCR-17-1544
   Web of Science ®Google Scholar
• Karakas C, Biernacka A, Bui T, et al. Cytoplasmic cyclin E and phospho–cyclin-dependent kinase 2 are biomarkers of aggressive breast cancer. Am J Pathol. 2016;186(7):1900–1912. doi:10.1016/j.ajpath.2016.02.024
   PubMed Web of Science ®Google Scholar
• Hunt KK, Karakas C, Ha MJ, et al. Cytoplasmic cyclin E predicts recurrence in patients with breast cancer. Clin Cancer Res. 2017;23(12):2991–3002. doi:10.1158/1078-0432.CCR-16-2217
   PubMed Web of Science ®Google Scholar
• J A-QA, Alves CL, Ehmsen S, et al. Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer. NPJ Precis Oncol. 2022;6(1):68. doi:10.1038/s41698-022-00311-6
   PubMed Web of Science ®Google Scholar
• Dawson SJ, Makretsov N, Blows FM, et al. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer. 2010;103(5):668–675. doi:10.1038/sj.bjc.6605736
   PubMed Web of Science ®Google Scholar
• Lok SW, Whittle JR, Vaillant F, et al. A phase IB dose-escalation and expansion study of the BCL2 inhibitor venetoclax combined with tamoxifen in ER and BCL2-positive metastatic breast cancer. Cancer Discov. 2019;9(3):354–369. doi:10.1158/2159-8290.CD-18-1151
   PubMed Web of Science ®Google Scholar
• Vaillant F, Merino D, Lee L, et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 2013;24(1):120–129. doi:10.1016/j.ccr.2013.06.002
   PubMed Web of Science ®Google Scholar
• Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: randomized Phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors - efficacy, safety, and biomarker results. Clin Cancer Res. 2022;28(15):3256–3267. doi:10.1158/1078-0432.CCR-21-3811
   PubMed Web of Science ®Google Scholar
• Guarducci C, Bonechi M, Benelli M, et al. Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2018;4:38. doi:10.1038/s41523-018-0092-4
   PubMed Web of Science ®Google Scholar
• Liu Y, Zhong X, Wan S, et al. p16INK4a expression in retinoblastoma: a marker of differentiation grade. Diagn Pathol. 2014;9(1):180. doi:10.1186/s13000-014-0180-1
   PubMedGoogle Scholar
• Formisano L, Lu Y, Servetto A, et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun. 2019;10(1):1373. doi:10.1038/s41467-019-09068-2
   PubMed Web of Science ®Google Scholar
• Drago JZ, Formisano L, Juric D, et al. FGFR1 amplification mediates endocrine resistance but retains TORC sensitivity in metastatic hormone receptor-positive (HR+) breast cancer. Clin Cancer Res. 2019;25(21):6443–6451. doi:10.1158/1078-0432.CCR-19-0138
   PubMed Web of Science ®Google Scholar
• Gong X, Du J, Parsons SH, et al. Aurora A kinase inhibition is synthetic lethal with loss of the RB1 tumor suppressor gene. Cancer Discov. 2019;9(2):248–263. doi:10.1158/2159-8290.CD-18-0469
   PubMed Web of Science ®Google Scholar
• Teh JLF, Cheng PF, Purwin TJ, et al. In vivo E2F reporting reveals efficacious schedules of MEK1/2-CDK4/6 targeting and mTOR-S6 resistance mechanisms. Cancer Discov. 2018;8(5):568–581. doi:10.1158/2159-8290.CD-17-0699
   PubMed Web of Science ®Google Scholar
• De Leeuw R, McNair C, Schiewer MJ, et al. MAPK reliance via acquired CDK4/6 inhibitor resistance in cancer. Clin Cancer Res. 2018;24(17):4201–4214. doi:10.1158/1078-0432.CCR-18-0410
   PubMed Web of Science ®Google Scholar
• Anderson EJ, Mollon LE, Dean JL, et al. A systematic review of the prevalence and diagnostic workup of PIK3CA mutations in HR+/HER2-metastatic breast cancer. Int J Breast Cancer. 2020;2020:3759179. doi:10.1155/2020/3759179
   PubMed Web of Science ®Google Scholar
• Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders, and cancer. N Engl J Med. 2018;379(21):2052–2062. doi:10.1056/NEJMra1704560
   PubMed Web of Science ®Google Scholar