30P - The prognostic value of low density neutrophils in breast cancer: Implications for therapeutic strategies

Background

Metastatic breast cancer (mBC) remains a leading cause of cancer-related deaths among women globally. Despite advances, many treatments fail to improve patient outcomes, emphasizing the need for innovative approaches and reliable biomarkers to better predict treatment response. Recent studies show that neutrophils play a critical role in cancer, with low density neutrophils (LDN) acting as key modulators in the tumor microenvironment. LDN are linked to tumor growth and metastasis, contributing to an immunosuppressive environment that supports cancer progression. Here, we investigated the clinical significance of LDN in breast cancer (BC) by assessing their association with disease progression and patient outcomes.

Methods

We analysed blood samples from 146 BC patients (78 non-metastatic, 68 metastatic), isolating both LDN and high-density neutrophils (HDN, conventional neutrophils) by density gradient centrifugation. Flow cytometry was used to quantify and characterize the populations.

Results

Our results show significant LDN accumulation in BC patients’ blood, particularly those with metastatic disease. Importantly, elevated LDN levels were linked to reduced life expectancy in these patients, regardless of metastatic site (bone, lung or brain). Moreover, the increase in LDN levels was often accompanied by a decrease in HDN, leading to an imbalance favoring protumor neutrophils. Additionally, preliminary data from a small cohort of triple-negative BC patients (n=7, ongoing recruitment) undergoing immunotherapy suggest that higher pre-treatment LDN levels may predict poorer treatment response. This early finding points to LDN’ potential as predictive biomarkers for immunotherapy efficacy in BC.

Conclusions

Our study highlights the prognostic value of LDN in BC, with elevated levels linked to advanced disease and worse clinical outcomes. These findings suggest that LDN could serve as valuable biomarkers for monitoring disease progression and predict treatment response, identifying patients at greater risk. Ultimately, incorporating LDN assessment into clinical practice may guide treatment strategies, offering a more personalized approach to BC management and potentially improving therapeutic outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.