Predictive and Prognostic Biomarkers for Response to Neoadjuvant Chemotherapy for Breast Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 380

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Guest Editor
Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
Interests: neoadjuvant chemotherapy; breast cancer
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Special Issue Information

Dear Colleagues,

Breast cancer (BC) is the most commonly occurring cancer in women, with 2.26 million new BC cases being diagnosed each year. Recently, BC has come to be considered as a heterogeneous group of tumours with regard to clinical presentation, epidemiology, histology, radiology, gene expression, prognosis, and response to treatment. Subsequently, the management of BC continues to present a significant clinical challenge, considering that these tumours often do not respond to targeted therapeutic agents and are more diverse than we originally thought.

Preoperative neoadjuvant cytotoxic chemotherapy (NACT) is a standard treatment option for triple-negative and HER2+ BC subtypes, in addition to HER2-targeting agents, as it downsizes tumours prior to loco-regional treatment with surgery and radiotherapy, provides an in vivo chemo-sensitivity test for the patient, and enables the deployment of more intensive adjuvant chemotherapy and the consideration of novel adjuvant treatment for chemo-resistant tumours. Monitoring tumour size reduction after each treatment cycle allows doctors to switch to a different chemotherapy regimen if standard drugs show no response or to fast-track the patient to undergoing immediate surgery. However, this relies on accurate clinical examination. With the current patient selection criteria and cycle-based response monitoring for NACT, only 30-50% of BC patients achieve a pCR (microscopic absence of tumour at surgery), which is generally associated with an excellent prognosis. Meanwhile, the remaining 50-70% patients with no pCR (residual disease) show a wide range of responses to NACT, from near-pCR to complete resistance, and diverse clinical outcomes (e.g., in terms of survival rates); posing a challenge in BC planning and management. Moreover, there is no reliable and efficient clinical pipeline to accurately stratify patients before, during, and after NACT according to the likelihood of treatment response and effectiveness.

Therefore, there is an urgent need to identify new prognostic and predictive features that could accurately sub-stratify BC, monitor and grade responses to chemotherapy, and tailor and guide treatment for individual patients to avoid serious toxicity and the economic burden on health systems caused by unnecessary ineffective therapies.

For this Special Issue, submissions of original research articles and reviews are welcome.

I look forward to receiving your contributions.

Dr. Tarek M. A. Abdel-Fatah
Guest Editor

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Keywords

  • breast cancer
  • predictive and prognostic biomarkers
  • neoadjuvant chemotherapy
  • HER2-targeting agents
  • complete pathological response

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Published Papers (1 paper)

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Research

18 pages, 2130 KiB  
Article
Personalizing Neoadjuvant Chemotherapy: The Impact of BRCA Variants on Pathologic Complete Response in Luminal B Breast Cancer
by Alba Di Leone, Antonio Franco, Virginia Castagnetta, Marta Silenzi, Cristina Accetta, Beatrice Carnassale, Sabatino D’Archi, Flavia De Lauretis, Enrico Di Guglielmo, Federica Gagliardi, Stefano Magno, Francesca Moschella, Maria Natale, Alejandro Martin Sanchez, Lorenzo Scardina, Riccardo Masetti and Gianluca Franceschini
Cancers 2025, 17(10), 1619; https://doi.org/10.3390/cancers17101619 - 10 May 2025
Viewed by 278
Abstract
Background: Neoadjuvant chemotherapy (NACT) is effective in downstaging locally advanced breast cancer, improving surgical and oncological outcomes. However, luminal B breast cancer typically exhibits a poorer response to NACT, with only 10–15% of patients achieving a pathologic complete response (pCR). This study [...] Read more.
Background: Neoadjuvant chemotherapy (NACT) is effective in downstaging locally advanced breast cancer, improving surgical and oncological outcomes. However, luminal B breast cancer typically exhibits a poorer response to NACT, with only 10–15% of patients achieving a pathologic complete response (pCR). This study investigates whether BRCA pathogenic variants (BRCA PVs) influence pCR rates in luminal B breast cancer patients, aiming to identify potential predictors for personalized treatment strategies. Materials and Methods: This retrospective study included luminal B breast cancer patients who underwent NACT at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2014 and June 2023. Patients were stratified according to BRCA status: BRCA PVs and BRCA wild-type (WT). Primary endpoint was to evaluate pCR rates, while secondary endpoints included locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS), and overall survival (OS). Results: In total, 495 patients were enrolled, of whom 442 (89.3%) carried BRCA WT and 53 (10.7%) BRCA PVs. The pCR rate was significantly higher in the BRCA PVs group (20.8% PVs vs. 10.9% WT; p = 0.044). Specifically, the breast pCR rate was 28.3% in BRCA PVs versus 15.4% in BRCA WT (p = 0.030). BRCA WT patients had better 5-year LR-DFS (91.1% WT vs. 79.5% PVs; p = 0.003), while no significant differences were observed in 5-year DDFS or OS. Conclusions: BRCA PVs are associated with a higher pCR rate in luminal B breast cancer patients receiving NACT, suggesting a potential predictive role in tailoring treatment strategies. Full article
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