الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the second most common cancer in the world and, by far, the most frequent among women. Genomic profiling has demonstrated the presence of discrete molecular subtypes with distinct immunohistochemical features and clinical behavior.
In the last decade our genetic view has been expanded by the observation that tumors are thriving organs with multiple cell types within a distinctive extracellular matrix (ECM), and that all these components can impact tumor progression and response to therapies. Over time, the tumor and the adjacent cells co-evolve and even metastasize together.
In our study we aimed to study TILS, for the first time in a population of Egyptian patients, using the International Immunooncology Biomarkers Working group guidelines. We were focused on correlating the TILS with clinicopathological characteristics, treatment and survival.
In our analysis using t-test and univariate linear regression we correlated high TILS with multiple factors that represented favorable tumor characteristics; such as unilateral rather than bilateral disease, low clinical tumor stage, negative lymph node status clinically or by mammography or clinical N stage, lymph node involvement and extracapsular extension by surgery. This shows us that the immune system plays an active role in preventing tumor progression, and that the more robust an immune response is the better the prognosis of the patient.
There was also a relationship between high TILS and high grade tumors which shows that this immune response is initiated by the immunogenecity of the tumor. The correlation between neoadjuvant chemotherapy and low TILS was displayed by 2 different parameters using both the t-test and univariate linear regression showed us that chemotherapy could cause depletion of the immune cells depending on the drug used. As when patients were treated with Anthracycline and Cyclophosphamide they maintained a significantly high TILS percentage, which results from the drug initiating immunogenic cell death in the tumor and decreasing immunosuppressive cells.
With triple-negative and HER-2 enriched breast cancers there were clinically significant HR for DFS, indicating that although these two molecular subtypes of tumors usually have worst prognosis, the presence of high TILS confers a much better chance for the tumor to respond to treatment and for decreasing the patient’s chance of having a disease recurrence.
We related the different characteristics to TILS as a continuous parameter, an incremental parameter and a binary parameter. The objective of this was to see whether there is an appropriate cut-off point for TILS that confers benefit. We proved that while there is a subgroup of patients that have exceptionally high TILS, called LPBC with TILS ≥50%, that results in exceptionally beneficial response to treatment and confers additional survival benefit; every incremental increase of 10% also resulted in benefit to treatment and delayed relapse.