الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Globally, breast cancer is the most commonly occurring malignancy among women
and the second most common cancer overall. In Egypt, breast cancer is the most frequently
common cancer among females.
Despite profound advances in management of breast cancer and the use of different
molecular markers to predict the prognosis to determine the treatment modalities, novel
prognostic and diagnostic markers are still required.
PD-L1, which is expressed on many cancer cells, plays an important role in blocking
―cancer-immunity cycle‖. PD-L1 complex is considered a major inhibitory pathway. It
suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and
restricts tumor killing.
This study aims to clarify the alteration of expression of PD-L1 in PBMCs of female
breast cancer patients and analyze its association with clinical pathological criteria as well
as therapeutic response to chemotherapy. Thus the potential use of PD-L1 gene expression
as a noninvasive predictive and prognostic biomarker could be investigated.
To fulfill the objectives, the study was conducted on 45 local advanced and
metastatic breast cancer patients after diagnosis and prior to the treatment, in addition to 45
female healthy volunteers. Additionally, the personal and clinical pathological data were
collected. While after the collection of peripheral blood samples, the molecular genetics
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study composed of the following main steps was performed. First, isolation of PBMCs
within one hour after sampling. Second, extraction of RNA which was performed
immediately after PBMCs isolation, otherwise the lysate was stored at -80◦C. Third,
reverse transcription was conducted where cDNA was synthesized. Finally, quantitative
real-time PCR was then conducted using SYBR Green DNA binding dye. Expression
levels of PD-L1 in breast cancer patients relative to controls were calculated using the
comparative Cq method (2–ΔΔCq) after normalization for the expression of GAPDH as
reference gene. Patients were followed up for assessment of response to chemotherapy
based on revised RECIST guidelines 1.1. Relative expression levels of PD-L1 were then
compared with personal data (age, menopausal state and family history) as well as with
clinicopathological parameters of the patients in addition to initial therapeutic response.
The distribution of the studied cases concerning personal data was summarized in
that fashion, the studied cases were divided into almost two equal groups according to age
(51.1% for <50 yrs and 48.9% for ≥50 yrs ) while according to menopausal state, 60% of
the patients were premenopausal. However, positive family history was stated by 8
patients.
Nevertheless, regarding clinicopathological criteria, all the local advanced breast
cancer patients were staged into stage III according to TNM staging and represented 51.5%
of all the studied breast cancer patients. Moreover, the dominance of IDC histological type
was noted with a percentage of 86.7% as well as the dominance of grade II by 71.1% with
complete absence of grade Ι. For the distribution of their hormonal profile, the percentages
of patients with ER –ve status, PR –ve status and HER-2 –ve status were 22.2 %, 35.6 %
and 42.2 % respectively. Furthermore, 55.6 % of the cases had high pretreatment
concentrations of CA15-3. Regarding the treatment, 71.1% received Adriamycin +
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Cyclophosphamide regimen (AC) and after the initial assessment, 64.4% of the patients
were responders.
A significant difference was detected for PD-L1 expression levels in breast cancer
patients compared to controls. Additionally, a notable PD-L1 overexpression was observed
in metastatic patients compared to local advanced breast cancer patients and controls.
Furthermore, correlation analysis of PD-L1 gene expression and personal data resulted in
the following: a significant association with age while no significance for menopausal state
and family history. Moreover, the results of correlation analysis with clinicopathological
parameters could be summed up as follows: a significant association with stage IV, ER
negative state, and high concentration of CA 15-3. On the other hand, no significant
correlation was observed for tumor size, lymph nodal status, histopathological type, grade,
PR status, HER-2 status, triple negative, among de novo and metastatic patients and for
number of metastatic sites as well as the therapeutic response.
It is noteworthy that the presented findings of the current study may pave the way for
the potential use of PD-L1 as a noninvasive biomarker for poor prognosis of breast cancer.