https://orcid.org/0009-0004-5608-1273
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ABSTRACT
Background
Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a comprehensive analysis for optimal therapy assessment. Therefore, a two-step Bayesian network meta-analysis (NMA) was performed to compare the efficacy and safety of different neoadjuvant regimens.
Research design and methods
Phase II/III randomized clinical trials comparing various neoadjuvant therapies for HR+/HER2- breast cancer were included. NMA and pairwise meta-analyses were conducted using Stata (version 14), R (version 4.2.3), and Review Manager 5.4.
Results
Twenty-eight studies (5,625 patients) were eligible. NMA of objective response rate (ORR) indicated the highest SUCRA for chemotherapy (CT) and chemotherapy with anthracycline (CT(A)). Pathologic complete response (PCR) NMA demonstrated significant PCR improvement with chemotherapy regimens containing programmed cell death protein-1 and programmed cell death ligand-1 inhibitors (PD-1i/PD-L1i) and poly ADP-ribose polymerase inhibitors (PARPi). Combined analysis considering both the ORR and safety highlighted CT(A)’s efficacy and toxicity balance.
Conclusions
CT(A) and CT showed improved ORR compared with alternative regimens. CT(A) combined with PD-1/PD-L1 or PARP inhibitors significantly increased PCR rates. Comprehensive assessment of both ORR and safety indicated that CT(A) represents an optimal neoadjuvant therapy for HR+/HER2- breast cancer, whereas AI + CDK4/6 inhibitors rank solely behind chemotherapy.
Registration
PROSPERO Registration: CRD42024538948. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number INPLASY202440092.
Abbreviations
| BC | = | Breast Cancer |
| MBC | = | Metastatic Breast Cancer |
| HR+/HER2- | = | Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative |
| ER+ | = | Estrogen Receptor Positive |
| CT | = | Chemotherapy |
| CT(A) | = | Chemotherapy (Anthracycline-based) |
| CDK4/6i | = | Cyclin-Dependent Kinase 4 and 6 Inhibitors |
| PARPi | = | Poly (ADP-Ribose) Polymerase Inhibitors |
| PD-1i | = | Programmed Cell Death Protein 1 Inhibitors |
| PD-L1i | = | Programmed Death-Ligand 1 Inhibitors |
| NAC | = | Neoadjuvant Chemotherapy |
| NET | = | Neoadjuvant Endocrine Therapy |
| ORR | = | Objective Response Rate |
| PCR | = | Pathological Complete Response |
| VEGFi | = | Vascular Endothelial Growth Factor Inhibitors |
| EGFRi | = | Epidermal Growth Factor Receptor Inhibitors |
| PI3Ki | = | Phosphoinositide 3-Kinase Inhibitors |
| BCS | = | Breast-Conserving Surgery |
| NMA | = | Network Meta-Analysis |
| PRISMA | = | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
| RCTs | = | Randomized Clinical Trials |
| NCI-CTC | = | National Cancer Institute Common Terminology Criteria |
| AJCC | = | American Joint Committee on Cancer |
| SUCRA | = | Surface Under the Cumulative Ranking |
| ROB | = | Risk of Bias |
| ICIs | = | Immune Checkpoint Inhibitors |
| AI | = | Aromatase Inhibitors |
| SERD | = | Selective Estrogen Receptor Downregulator |
| SERM | = | Selective Estrogen Receptor Modulator |
| GnRHa | = | Gonadotropin-Releasing Hormone Agonists |
| NCCN | = | National Comprehensive Cancer Network |
| CCCA | = | Complete Cell Cycle Arrest |
| ALT | = | Alanine Aminotransferase |
| RTK | = | Receptor Tyrosine Kinase |
| FDA | = | Food and Drug Administration |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
R Chen and Y Yu contributed equally to this study. C Song and R Chen conceived this study. R Chen, Y Yu, and J Zhang had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Y Yu and C Wang designed the search strategy. R Chen and J Zhang screened the abstracts and full texts, acquired the data, and determined the risk of bias in the studies. R Chen and Y Yu performed the data analysis. R Chen and Y Yu wrote the first drafts of the manuscript. C Wang, J Zhang, and C Song critically revised the manuscript. All the authors approved the final version of the manuscript.
Acknowledgments
We gratefully acknowledge Editage for their editing support.
Data availability statement
All data generated or analyzed in this study are included in the published article and supplementary information files.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2024.2350105.