The role of CDK4/6 inhibitors in early breast cancer

Gil-Gil, Miguel; Alba, Emilio; Gavilá, Joaquín; Haba, Juan de la; Ciruelos, Eva; Tolosa, Pablo; Candini, D.; Llombart–Cussac, Antonio

doi:10.1016/j.breast.2021.05.008

Cited by 21 publications

(12 citation statements)

References 76 publications

(131 reference statements)

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“…Although the use of CDK4/6 inhibitors is currently limited to the metastatic setting, there are ongoing efforts to evaluate the efficacy of CDK4/6 inhibitors in the upfront setting for women with locally advanced or high-risk ER+ disease [ 71 ]. In contrast to the conventional use of CDK4/6 inhibitors in the metastatic setting, Pesh et al recently studied the effects of CDKi and radiation (RT) in multiple preclinical BC models [ 72 ].…”

Section: Resultsmentioning

confidence: 99%

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

Beddok

Cottu

Kirova

2021

Cancers

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Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT). Methods: Preclinical and clinical studies investigating this combination were extensively reviewed. Results: Several studies showed that the combination of RT and tamoxifen increased the risk of radiation-induced pulmonary toxicity; therefore, both modalities should not be given concomitantly. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and RT seems to be safe. However, trastuzumab emtansine (T-DM1) should not be administered concurrently with brain RT since this combination could increase the risk of brain radionecrosis. The combination of RT and other new target treatments such as selective estrogen receptor degradants, lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but was essentially evaluated on retrospective or prospective studies with a small number of patients. Furthermore, there is considerable heterogeneity among these studies regarding the dose and fractionation of radiation, the dosage of drugs, and the sequence of treatments used. Conclusions: The combination of RT with most targeted therapies for BC appears to be well-tolerated, but these results need to be confirmed in prospective randomized studies.

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Section: Resultsmentioning

confidence: 99%

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

Beddok

Cottu

Kirova

2021

Cancers

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“…With the increasing utilization of CDK4/6 inhibitors in the most common subset of mBC (HR + /HER2 − ), and their recent approval in HER2-positive disease, 44 in addition to the recent efforts to move their use to earlier stages of breast cancer, 45 CDK4/6 inhibitor-induced vitiligo-like lesions will probably be more commonly encountered.…”

Section: Discussionmentioning

confidence: 99%

Vitiligo-Like Lesions in a Patient with Metastatic Breast Cancer Treated with Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor: A Case Report and Literature Review

Sharaf¹,

AlMasri²,

Abdel-Razeq³

et al. 2022

CCID

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Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2 − ) metastatic breast cancer, with an impressive efficacy and safety profile. Cytopenia is the main adverse event, which is both predictable and manageable. Here, we report a case of CDK4/6 inhibitor-induced vitiligo-like lesions. Vitiligo or vitiligolike lesions are a rare adverse event; only a few cases are reported in the literature. Case Presentation: A 71-year-old female patient was diagnosed initially with early-stage right breast cancer (HR + /HER2 − ) and was treated with breast-conserving surgery followed by chemotherapy, radiotherapy, and hormonal therapy. A few years later, she developed metastatic disease to the hilar lymph nodes, and to multiple skeletal sites, including the left scapula, left shoulder, left iliac bone, and dorsal vertebrae, for which she was treated with ribociclib and letrozole. While on treatment, she developed hypopigmented lesions involving both hands, feet, and face, which were described as vitiligo-like lesions. Conclusion: CDK4/6 inhibitor-induced vitiligo is a rare and unpredictable adverse event. This case report highlights the rarity of this adverse event, the dilemma related to the optimal treatment, and decisions related to continuation, holding, or switching CDK4/6 inhibitors.

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“…In many malignant tumors, especially ER-positive breast cancer, the high expression of CDK4/6 promotes excessive proliferation of cancer cells, whereas CDK4/6 inhibitors can block the cell cycle in the S phase, thereby inhibiting tumor cell proliferation. 226 CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, combined with anti-estrogens have shown significant progress-free survival (PFS) benefits, which may be due to the effect of breast cancer cells on cyclin D1 special dependence and estrogen-mediated activation of CDKs. 227 , 228 , 229 Like all other treatment strategies, the emergence of CDK inhibitor resistance is an obstacle in clinical breast cancer treatment.…”

Section: The Role Of Lncrna In Breast Cancer Malignant Progressmentioning

confidence: 99%

lncRNA and breast cancer: Progress from identifying mechanisms to challenges and opportunities of clinical treatment

Jin

Huang

et al. 2021

Molecular Therapy - Nucleic Acids

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Breast cancer is a malignant tumor that has a high mortality rate and mostly occurs in women. Although significant progress has been made in the implementation of personalized treatment strategies for molecular subtypes in breast cancer, the therapeutic response is often not satisfactory. Studies have reported that long non-coding RNAs (lncRNAs) are abnormally expressed in breast cancer and closely related to the occurrence and development of breast cancer. In addition, the high tissue and cell-type specificity makes lncRNAs particularly attractive as diagnostic biomarkers, prognostic factors, and specific therapeutic targets. Therefore, an in-depth understanding of the regulatory mechanisms of lncRNAs in breast cancer is essential for developing new treatment strategies. In this review, we systematically elucidate the general characteristics, potential mechanisms, and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer. Additionally, we also highlight the advantages and challenges of using lncRNAs as biomarkers for diagnosis or therapeutic targets for drug resistance in breast cancer and present future perspectives in clinical practice.Long non-coding RNAs (lncRNAs) are originally thought to be the noise of transcripts in the genome and have no biological function. Recently, the function of lncRNAs is beginning to attract widespread attention. 7 Increasing studies have shown that lncRNAs are involved in various aspects of cellular physiological processes, such as proliferation, differentiation, migration, and apoptosis, by regulating gene transcription and post-transcriptional processing. 8,9 In addition, lncRNAs are closely related to the occurrence, development, and prognosis of various cancers, such as breast, liver, colon, and lung cancer and even leukemia. [10][11][12][13] According to lncRNA genomic position, subcellular localization, and function, they can be divided into six types (Figure 1). 14 (1) Enhancer lncRNAs are derived from the promoter enhancer region, such as lncRNA-LEENE. 15 (2) Intron lncRNAs are transcribed from the intron region of the gene. The gene-coding protein completely contained the intron lncRNA, which can stabilize the transcription or regulate the alternative splicing of the coding gene. (3) Antisense lncRNA: its transcription orientation is opposite to the transcription orientation of the adjacent protein-encoding gene, such as lncTALAM1 and PDCD4-AS1. 16,17 (4) The sense lncRNA: its transcription orientation is the same as that of the adjacent protein-encoding gene, such as lncRNAGAS5 and ecCEPBA. 18,19 (5) Intergenic lncRNA, which can be transcribed between two protein-coding genes, is an autonomously transcribed

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The role of CDK4/6 inhibitors in early breast cancer

Cited by 21 publications

References 76 publications

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

Vitiligo-Like Lesions in a Patient with Metastatic Breast Cancer Treated with Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor: A Case Report and Literature Review

lncRNA and breast cancer: Progress from identifying mechanisms to challenges and opportunities of clinical treatment

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