Long‑term progression‑free survival in HR+/HER2+ advanced breast cancer with combination therapy with a CDK4/6 inhibitor and first‑line maintenance therapy: A case report

Cai,Yihong; Zhang,Jinling; Duan,Hongxia; Liu,Fan

doi:10.3892/ol.2025.14973

Long‑term progression‑free survival in HR+/HER2+ advanced breast cancer with combination therapy with a CDK4/6 inhibitor and first‑line maintenance therapy: A case report

Authors:
- Yihong Cai
- Jinling Zhang
- Hongxia Duan
- Fan Liu
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Affiliations: Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China, Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
Published online on: March 10, 2025 https://doi.org/10.3892/ol.2025.14973
Article Number: 227
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The current standard treatment for hormone receptor (HR)‑positive and human epidermal growth factor receptor 2 (HER2)‑positive advanced breast cancer (BC) involves the use of anti‑HER2 monoclonal antibodies combined with chemotherapy, followed by sequential endocrine therapy. However, crosstalk between the HR and HER2 pathways may cause drug resistance. Combining therapies targeting both the HR and HER2 pathways may be a rational approach for patients with HR⁺/HER2⁺ tumors, as this strategy could counteract resistance by blocking crosstalk in the receptor pathway. However, clinical data in this field remain limited. The present report describes the case of a patient with HR⁺/HER2⁺ late‑stage BC who achieved a long‑term partial response rate after receiving anti‑HER2 combination chemotherapy followed by sequential treatment with endocrine therapy and cyclin‑dependent kinase 4/6 (CDK4/6) inhibitors. The present case provides additional evidence suggesting that incorporating CDK4/6 inhibitors into standard targeted chemotherapy regimens may be an effective treatment option for patients with HR⁺/HER2⁺ BC.

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1	Chen H, Gui X, Zhou Z, Su F, Gong C, Li S, Wu W, Rao N, Liu Q and Yao H: Distinct ER and PR expression patterns significantly affect the clinical outcomes of early HER2-positive breast cancer: A real-world analysis of 871 patients treated with neoadjuvant therapy. Breast. 75:1037332024. View Article : Google Scholar : PubMed/NCBI
2	Dai X, Cheng H, Bai Z and Li J: Breast cancer cell line classification and its relevance with breast tumor subtyping. J Cancer. 8:3131–3141. 2017. View Article : Google Scholar : PubMed/NCBI
3	Vici P, Pizzuti L, Sperduti I, Frassoldati A, Natoli C, Gamucci T, Tomao S, Michelotti A, Moscetti L, Gori S, et al: ‘Triple positive’ early breast cancer: an observational multicenter retrospective analysis of outcome. Oncotarget. 7:17932–17944. 2016. View Article : Google Scholar : PubMed/NCBI
4	Larionov AA: Current therapies for human epidermal growth factor receptor 2-positive metastatic breast cancer patients. Front Oncol. 8:892018. View Article : Google Scholar : PubMed/NCBI
5	Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, et al: 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. Breast Cancer Res. 11:R772009. View Article : Google Scholar : PubMed/NCBI
6	Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, et al: Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors. Cancer Cell. 29:255–269. 2016. View Article : Google Scholar : PubMed/NCBI
7	Tolaney SM, Goel S, Nadal J, Denys H, Borrego MR, Litchfield LM, Liu J, Appiah AK, Chen Y and André F: Overall survival and exploratory biomarker analyses of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus chemotherapy in HR+, HER2+ metastatic breast cancer patients. Clin Cancer Res. 30:39–49. 2024. View Article : Google Scholar : PubMed/NCBI
8	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. 375:1925–1936. 2016. View Article : Google Scholar : PubMed/NCBI
9	Choi YJ, Li X, Hydbring P, Sanda T, Stefano J, Christie AL, Signoretti S, Look AT, Kung AL, von Boehmer H and Sicinski P: The requirement for cyclin D function in tumor maintenance. Cancer Cell. 22:438–451. 2012. View Article : Google Scholar : PubMed/NCBI
10	Sherr CJ and Roberts JM: Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 18:2699–2711. 2004. View Article : Google Scholar : PubMed/NCBI
11	Roberts PJ, Bisi JE, Strum JC, Combest AJ, Darr DB, Usary JE, Zamboni WC, Wong KK, Perou CM and Sharpless NE: Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J Natl Cancer Inst. 104:476–487. 2012. View Article : Google Scholar : PubMed/NCBI
12	Witkiewicz AK, Cox D and Knudsen ES: CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models. Genes Cancer. 5:261–272. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yan M, Niu L, Lv H, Zhang M, Wang J, Liu Z, Chen X, Lu Z, Zhang C, Zeng H, et al: Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: A single-arm phase II trial. Nat Commun. 14:62722023. View Article : Google Scholar : PubMed/NCBI
14	Sawaki M, Shien T and Iwata H: TNMclassification of malignant tumors (Breast Cancer Study Group). Jpn J Clin Oncol. 49:228–231. 2019. View Article : Google Scholar : PubMed/NCBI
15	Li J and Jiang Z: Chinese society of clinical oncology breast cancer (CSCO BC) guidelines in 2022: Stratification and classification. Cancer Biol Med. 19:769–773. 2022. View Article : Google Scholar : PubMed/NCBI
16	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
17	Zhang C, Zhou F, Zou J, Fang Y, Liu Y, Li L, Hou J, Wang G, Wang H, Lai X, et al: Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer. Front Oncol. 13:13220782024. View Article : Google Scholar : PubMed/NCBI
18	Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, et al: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 366:109–119. 2012. View Article : Google Scholar : PubMed/NCBI
19	Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA III, et al: Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results from MARIANNE. Cancer. 125:3974–3984. 2019. View Article : Google Scholar : PubMed/NCBI
20	Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, et al: Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: Results from the randomized phase III TAnDEM study. J Clin Oncol. 27:5529–5537. 2009. View Article : Google Scholar : PubMed/NCBI
21	Johnston S, Pippen J, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, et al: Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 27:5538–5546. 2009. View Article : Google Scholar : PubMed/NCBI
22	Glaviano A, Wander SA, Baird RD, Yap KCH, Lam HY, Toi M, Carbone D, Geoerger B, Serra V, Jones RH, et al: Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment. Drug Resist Updat. 76:1011032024. View Article : Google Scholar : PubMed/NCBI
23	Pilehvari A, Kimmick G, You W, Bonilla G and Anderson R: Disparities in receipt of 1-st line CDK4/6 inhibitors with endocrine therapy for treatment of hormone receptor positive, HER2 negative metastatic breast cancer in the real-world setting. Breast Cancer Res. 26:1442024. View Article : Google Scholar : PubMed/NCBI
24	Kumar R, Gururaj AE, Vadlamudi RK and Rayala SK: The clinical relevance of steroid hormone receptor corepressors. Clin Cancer Res. 11:2822–2831. 2005. View Article : Google Scholar : PubMed/NCBI
25	Iqbal N and Iqbal N: Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications. Mol Biol Int. 2014:1–9. 2014. View Article : Google Scholar : PubMed/NCBI
26	Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H and Schiff R: Mechanisms of tamoxifen resistance: Increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst. 96:926–935. 2004. View Article : Google Scholar : PubMed/NCBI
27	O'Sullivan CC, Suman VJ and Goetz MP: The emerging role of CDK4/6i in HER2-positive breast cancer. Ther Adv Med Oncol. 11:1758835919887662019.
28	Vinciguerra GL, Sonego M, Segatto I, Dall'Acqua A, Vecchione A, Baldassarre G and Belletti B: CDK4/6 Inhibitors in combination therapies: Better in company than alone: A mini review. Front Oncol. 12:8915802022. View Article : Google Scholar : PubMed/NCBI
29	Huo S, Xue J, Wang S, Shan H, Chen G, Niu N, Wang Y, Qiu F, Zhao Y, Xing F, et al: A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer. MedComm (2020). 5:e5052024. View Article : Google Scholar : PubMed/NCBI
30	Ciruelos E, Villagrasa P, Pascual T, Oliveira M, Pernas S, Paré L, Escrivá-de-Romaní S, Manso L, Adamo B, Martínez E, et al: Palbociclib and trastuzumab in HER2-Positive advanced breast cancer: Results from the phase II SOLTI-1303 PATRICIA Trial. Clin Cancer Res. 26:5820–5829. 2020. View Article : Google Scholar : PubMed/NCBI
31	Xue Y and Zhai J: Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance. Int J Clin Exp Pathol. 17:189–207. 2024. View Article : Google Scholar : PubMed/NCBI
32	Cen L, Carlson BL, Schroeder MA, Ostrem JL, Kitange GJ, Mladek AC, Fink SR, Decker PA, Wu W, Kim JS, et al: p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 14:870–881. 2012. View Article : Google Scholar : PubMed/NCBI
33	Wang H, Ba J, Kang Y, Gong Z, Liang T, Zhang Y, Qi J and Wang J: Recent progress in CDK4/6 inhibitors and PROTACs. Molecules. 28:80602023. View Article : Google Scholar : PubMed/NCBI