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PARP1, BRCA1 and androgen receptor expression in triple-negative breast cancer patients treated with neoadjuvant chemotherapy
Faculty
Medicine
Year:
2022
Type of Publication:
ZU Hosted
Pages:
Authors:
Nelly Mohammed Saeed Abdul Rahman Muhammed
Journal:
Revista de Senología y Patología Mamaria Elsevier
Volume:
Keywords :
PARP1, BRCA1 , androgen receptor expression in triple-negative
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype, where no effective therapies have been established for it. Searching for therapeutic targets for TNBC patients is the aim of the current research. Poly adenosine diphosphate ribose polymerase (PARP1) inhibitors are promising antitumor therapy that have a high potency in BRCA1-deficient breast cancers. Materials and Methods: Forty TNBC patients who received neoadjuvant chemotherapy (NAC) were enrolled in this study, and evaluated for PARP1, BRCA1, and Androgen receptor (AR) immunohistochemical expression before and after receiving NAC. Data of patients’ clinical and pathological responses to the chemotherapy were collected and finally analyzed. Results: The immunohistochemical results revealed 10 cases (25%) positive for AR, while 18 cases (45%) and 22 cases (55%) expressed PARP1 at low and high levels, respectively. Twelve cases (30%) and 28 cases (70%) expressed BRCA1 at low and high levels, respectively. There was a significant difference between PARP1 expression in normal and malignant tissues (P <0.001). Higher PARP1 expression was correlated with a better overall clinical response (OAR) and pathological complete response (pCR) ( P = 0.018, 0.01 respectively). Co-expression of both PARP1 & BRCA1 was correlated with OAR and pCR. Chemotherapy decreases PARP1 protein levels in matched patient samples (P = 0.015). Positive AR expression was correlated with BRCA1 overexpression. Conclusion: PARP1 is highly expressed in TNBC with a better OAR and pCR especially in cases with high BRCA1, so it might be considered as a therapeutic target for this risky group.
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