Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Mar 16:16:727-735.
doi: 10.2147/DDDT.S356757. eCollection 2022.

Expanding the Clinical Use of CDK4/6 Inhibitors in the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer from Metastatic Setting to Adjuvant Setting

Hikmat Abdel-Razeq  1   2 , Baha' Sharaf  1
Affiliations
Review

Expanding the Clinical Use of CDK4/6 Inhibitors in the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer from Metastatic Setting to Adjuvant Setting

Hikmat Abdel-Razeq et al. Drug Des Devel Ther. .

Abstract

More than two-thirds of patients with breast cancer present with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative disease at their initial diagnosis. HR-positive breast cancer's growth depends on Cyclin D1, a direct transcriptional target of estrogen receptors (ER). The recent introduction of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib, ribociclib, and abemaciclib) has revolutionized the treatment of metastatic HR-positive, HER2-negative breast cancer in both endocrine-sensitive and endocrine-resistant settings and in both pre-and post-menopausal women. Multiple large randomized clinical trials had demonstrated improvement in progression-free survival (PFS) and, more recently, in overall survival (OS). Adjuvant endocrine therapy (ET) significantly reduces the risk of recurrence and death among patients with HR-positive early-stage breast cancer (EBC). However, up to 20% of these patients will experience local, regional or distal recurrences in the first ten years. Such resistance to ET motivated researchers to try CDK4/6 inhibitors in EBC, both in adjuvant and neoadjuvant settings. While many clinical trials are still ongoing, at least one study and two meta-analyses had shown beneficial results, based on which the US Food and Drug Administration had recently approved the use of one of these agents, abemaciclib, in combination with ET for the adjuvant therapy of patients with high-risk EBC. In this paper, we review the recently published and ongoing landmark clinical trials attempting to expand the use of CDK4/6 inhibitors, in combination with ET, in the adjuvant setting of EBC.

Keywords: CDK4/6 inhibitors; abemaciclib; adjuvant; early-stage breast cancer; palbociclib; ribociclib.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The PALLAS versus the MonarachE trial. More patients in the MonarachE trial had higher risk features including Stage-III, Grade-III and positive lymph nodes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung H, Ferlay J, Siegel R, 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 - DOI - PubMed
    1. Lei S, Zheng R, Zhang S, et al. Global patterns of breast cancer incidence and mortality: a population‐based cancer registry data analysis from 2000 to 2020. Cancer Commun. 2021;41(11):1183–1194. doi:10.1002/cac2.12207 - DOI - PMC - PubMed
    1. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021;149(4):778–789. doi:10.1002/ijc.33588 - DOI - PubMed
    1. Luo C, Li N, Lu B, et al. Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019. Chin Med J. 2021;135(1):42–51. doi:10.1097/cm9.0000000000001814 - DOI - PMC - PubMed
    1. Howlader N, Altekruse S, Li C, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055 - DOI - PMC - PubMed

Grants and funding

There is no funding to report.