الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The most frequent occuring cancer among women is breast cancer. Annually, 2.3
million new cases of BC are thought to be diagnosed worldwide. In Egypt, 38.8% of all
cancers are BC patients, with a mortality rate of around 11%.
A little more than 80% of BC patients are over 50 years. Over the past three decades,
cancer incidence and death rates have increased as a result of changes in risk factor profiles,
enhanced cancer registration, and improved cancer detection. Treatment for breast cancer is
complex and calls for a number of modalities, including surgery, radiotherapy, chemotherapy,
hormone therapy, or biological therapies, all of which are given in a different sequence.
The majority of myeloid leukocytes, which typically make up between 50% and 70% of
all white blood cells, are neutrophils. Neutrophils have previously been thought of as
unreactive bystander cells in cancer formation and metastasis. However, it was discovered
that neutrophils are capable of a unique immune response in which they discharge their DNA
and other intracellular contents in a web-like structure known as neutrophil extracellular traps
(NET). Increased NET production or decreased NET removal may encourage vascular
disease, autoimmunity, and inflammation, and can contribute to cancer growth and
progression. In a study with Ewing sarcoma patients, 25% of cases developed NETs inside the
tumor, and metastases, showing that NETs may enhance tumor progression. Therefore, it is
anticipated that reducing NET production will have therapeutic effects on various illnesses
and disorders.
NETs are made up of decondensed chromatin DNA and the contents of granules like
MPO, NE, leukocyte proteinase 3, cathepsin G, lactoferrin, lysozyme C, neutrophil defensins,
and others, which are specific proteins can be measured in serum.
The PD-1 receptor and its ligand, PD-L1, serve as an immune checkpoint pathway with
important therapeutic significance. The expression of PD-L1 is advantageous to tumor cells
because it prevents immune cells from proliferating and becoming activated. The role of PD-
L1+ neutrophils is linked with a tumor-promoting phenotype because they block cytotoxic T
cells and may also mediate the inhibition of neutrophil cytotoxicity so enhance disease
progression and shorten patient survival. Neutrophil cytotoxicity is enhanced in tumor cells
when the PD-1/PD-L1 interaction is blocked.
The current study included 45 females who were divided into 30 breast cancer patients
in different stages of the disease and 15 age-matched healthy females as a control group.
Venous blood samples were taken from each subject under study in order to measure
myeloperoxidase (MPO) and neutrophil elastase (NE) in culture supernatants after
neutrophils’ culture with and without anti-PD-1 using enzyme-linked immunosorbent assay
(ELISA) and for biochemical investigations.
Our results showed a statistically significant difference between the early and late-stage
groups regarding tumor size and lymph node involvement. Also, results revealed that
treatment with anti-PD-1 was associated with a statistically significant decrease in the means
of NE and MPO concentrations in patients compared to healthy individuals. Moreover, we
Summary, Conclusions & Recommendations
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analyzed the association between NE and MPO where the results revealed a significant
positive correlation between NE and MPO concentration in treated neutrophils of early-stage
patients. Finally, we can suggest a potential role for anti-PD1 therapy in breast cancer
patients.