This Research Topic aims to provide a comprehensive historical review of the development and evolution of neoadjuvant chemotherapy in breast cancer treatment. By exploring key milestones, breakthroughs, and paradigm shifts, this Topic will trace the trajectory from early chemotherapy protocols to modern, personalised approaches.
Neoadjuvant chemotherapy (NAC) has transformed from a treatment option primarily used in inoperable or locally advanced breast cancer to a standard component of care in many early-stage cases. Its evolution has paralleled advancements in breast cancer subtyping, imaging technologies, and our understanding of tumour biology. Historically, NAC provided a valuable opportunity to downstage tumours and increase breast-conserving surgery eligibility. Today, it is also used as a tool to assess real-time tumour response and tailor subsequent treatment strategies, including the use of adjuvant therapies based on pathologic complete response (pCR).
This Research Topic will delve into the progression of clinical trial design, the introduction of biologic and targeted agents such as HER2-directed therapies, and the integration of NAC with surgical and radiation approaches. Contributors are encouraged to explore how NAC has improved outcomes in aggressive subtypes like triple-negative and HER2-positive breast cancer, and how it is shaping treatment de-escalation The Topic will also examine key challenges faced during the evolution of NAC, including heterogeneity in treatment response, the emergence of resistance mechanisms, and the need for validated predictive biomarkers. Through a critical lens, the Topic aims to reflect on how lessons learned from past clinical trials and real-world data can guide ongoing innovation in neoadjuvant strategies, with a focus on optimizing outcomes and personalising therapy further.
This project welcomes contributions that provide historical insights as well as forward-looking perspectives. Themes of interest include:
- Historical development of NAC protocols and their clinical impact
- Landmark clinical trials that shaped NAC in different breast cancer subtypes
- Introduction and role of targeted therapies and immunotherapy in NAC
- Use of pCR as a surrogate endpoint and its clinical implications
- Role of NAC in surgical planning and decision-making
- Biomarkers, imaging tools, and predictors of response
- Mechanisms of chemotherapy resistance and future directions
- Global disparities in NAC use and access
Authors are welcome to submit the following manuscript types to this Research Topic; Original Research, Reviews, Mini Reviews, Perspectives, and Clinical Trial articles. By contextualising past achievements, this Research Topic seeks to inform future research and clinical application in the breast cancer space. Contributions should highlight how the historical evolution of NAC has shaped modern clinical practices and where opportunities for progress still lie.
Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

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Neoadjuvant Chemotherapy in Breast Cancer: A Historical Journey of Evolution and Innovation