The Prognostic and Predictive Significance of PARP-1 in Locally Advanced Breast Cancer of Egyptian Patients Receiving Neoadjuvant Chemotherapy

Aiad, Hayam A; Kandil, Mohamed; El-Tahmody, Mohammed A.; Abulkheir, Iman Loay Hussein; Abulkasem, Fatma M.; Elmansori, Asma A.; Aleskandarany, Mohammed A.

doi:10.1097/pai.0000000000000124

Cited by 9 publications

(16 citation statements)

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“…After reviewing the complete text of the remaining 31 articles, 23 were excluded for the following reasons: review (10), no study endpoint (7), and insufficient data (6). Finally, a total of 3506 patients from eight eligible studies were included[ 7 – 9 , 15 – 19 ]. The details of the selection process are presented in Fig 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Recently, researchers reported that PARP inhibitors could be used to treat TNBC[ 6 ]; however, the relationship between the PARP expression level and TNBC is unclear. Recent studies have suggested that PARP over-expression is a poor prognostic marker for breast cancer survival[ 7 , 8 ]; nonetheless, contradictory evidence also has been reported[ 9 ]. These conflicting conclusions regarding the association between PARP expression and breast cancer clearly indicate the need for further investigation before application of this marker in future breast cancer diagnosis, treatment, and prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic and clinicopathological value of poly (adenosine diphosphate-ribose) polymerase expression in breast cancer: A meta-analysis

et al. 2017

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BackgroundPrevious studies have shown that the poly (adenosine diphosphate-ribose) polymerase (PARP) level is a promising indicator of breast cancer. However, its prognostic value remains controversial. The present meta-analysis evaluated the prognostic value of PARP expression in breast cancer.Materials and methodsEligible studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane Library databases through July 20, 2016. Studies investigating PARP expression as well as reporting survival data in breast cancer were included. Two independent reviewers carried out all literature searches. The pooled relative risk (RR) and hazard ratio (HR) with 95% confidence interval (95% CI) were applied to assess the association between PARP expression and the clinicopathological features and survival outcome in breast cancer.ResultsA total of 3506 patients from eight eligible studies were included. We found that higher PARP expression indicated a worse clinical outcome in early stage breast cancer, with a HR of 3.08 (95% CI, 1.14–8.29, P = 0.03) for disease-free survival and a HR of 1.82 (95% CI, 1.20–2.76; P = 0.005) for overall survival. Moreover, increased PARP expression was significantly associated with higher nuclear grade (RR, 1.51; 95% CI, 1.12–2.04; P = 0.008) in breast cancer. A similar correlation was detected in triple-negative breast cancer (TNBC; RR, 1.81; 95% CI, 1.04–3.17; P = 0.04).ConclusionsOur findings indicated that elevated PARP expression correlated with worse prognosis in early stage breast cancer. Furthermore, high PARP expression was associated with higher nuclear grade and TNBC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic and clinicopathological value of poly (adenosine diphosphate-ribose) polymerase expression in breast cancer: A meta-analysis

et al. 2017

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“…However, Aiad et al (43) demonstrated that high nuclear PARP-1 expression levels were significantly associated with improved OS in locally advanced breast cancer; Klauschen et al (44) demonstrated that low nuclear expression levels of PARP were associated with a poor prognosis in pancreatic cancer. These previous studies indicated that PARP-1 expression had differing roles in between different tumor types and stages of the tumors.…”

Section: Discussionmentioning

confidence: 99%

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu

Zhao

et al. 2016

Oncology Letters

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Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously demonstrated to be overexpressed in numerous malignant tumors and associated with invasiveness and poor prognosis. However, the expression of the PARP-1 protein in gastric cancer and its association with clinical outcomes requires further investigation. In the present study, the expression of PARP-1 in 564 gastric cancer tissues and 335 tumor-adjacent control tissues is investigated, using tissue microarray-based immunohistochemistry. PARP-1 expression levels were demonstrated to be significantly higher in gastric cancer tissue samples, as compared with control tissue samples. In gastric cancer, high PARP-1 expression levels were significantly associated with Helicobacter pylori (H. pylori) infection (P=0.032), decreased differentiation (P<0.001), increased depth of invasion (P=0.037), presence of lymphatic invasion (P<0.001), presence of lymph node metastasis (P<0.001), and advanced tumor-node-metastasis (TNM) stage (P=0.015). High PARP-1 expression levels were associated with a significantly shorter overall survival rate (P<0.001) and disease-free survival rate (P=0.001) in patients with gastric cancer, particularly a subset of patients with H. pylori infection or an advanced TNM stage. In addition, univariate analysis indicated that PARP-1 high expression levels were significantly associated with a poor prognosis in gastric cancer. These results suggest that PARP-1 expression may be involved in the progression and prognosis of gastric cancer, particularly H. pylori-positive or advanced-stage gastric cancer.

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“…Donizy et al reported that nuclear-cytoplasm expression (NCE) of PARP-1 was associated with unfavorable prognosis in lymph node negative early breast cancer 21 . While in Aiad's study, the authors demonstrated that PARP-1 immunohistochemical expression is a marker of good prognosis in locally advanced breast cancer 22 . A meta-analysis included 3506 patients from eight studies, the results indicated that higher PARP expression indicated a worse clinical outcome in early stage breast cancer, with a HR of 3.08 (95% CI, 1.14 ± 8.29, P = 0.03) for disease-free survival and a HR of 1.82 (95% CI, 1.20 ± 2.76; P = 0.005) for overall survival 23 .…”

Section: Discussionmentioning

confidence: 97%

“…In their study, patients with high nPARP1 expression were more sensitive to anthracycline/taxane based neoadjuvant chemotherapy and with higher pathologic responses 14 . Results from Egyptian researchers also demonstrated that PARP1 immunohistochemical expression is predictive of response to anthracycline/taxane based neoadjuvant chemotherapy in locally advanced breast cancer patients 22 . As PARP1 involves in repairing DNA double-strand breaks, it is easy for us to understand its influence on sensitivity of agents which cause DNA damage, such as anthracyclines.…”

Section: Discussionmentioning

confidence: 97%

Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy

Liao

et al. 2020

Sci Rep

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triple-negative breast cancer (tnBc) is a highly aggressive disease and of poor prognosis. it is very important to identify novel biomarkers to predict therapeutic response and outcome of tnBc. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/ taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280-0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than tt genotype carriers (P = 0.016, HR 0.261 95% CI 0.088-0.778) and DFS of rs7531668 AA genotype carriers was shorter than tt genotype carriers (P = 0.015, HR 3.361 95% CI 1.259-8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170-0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063-7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974-33.243) were demonstrated to be independent prognostic factors. our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy.Breast cancer is one of the most common cancers and is the leading cause of cancer-related death in women around the world 1 . According to molecular profile, breast cancer was divided into several intrinsic subtypes: luminal-A, luminal-B, HER2-enriched, basal-like, and a normal breast-like group 2 . Triple negative breast cancer (TNBC) is defined as lacking expression of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). It accounts for 15-20% of all breast cancers and is characterized by enhanced aggressiveness, young age of onset and poor prognosis 3 . All intrinsic subtypes can be found in TNBC, but 50%-75% of TNBC have basal phenotype 4 . Recently, four to six distinct subtypes have been defined within TNBC, such as basal-like and claudin-low 5 . Chemotherapy remains the main treatment for TNBC, but the overall survival for metastatic TNBC is only 13-18 months 6 . Though PARP inhibitors showed promising effect in BRCA mutation patients, their effectiveness in TNBC need to be further verified. So it is very important for us to explore novel biomarkers and potential therapeutic targets in TNBC patients 7 .DNA damage caused by exogenous and endogenous factors plays an important role in carcinogenesis 8 . Multiple DNA repair pathways are vital for controlling DNA damage and maintaining genomic stability, such as base excision repair (BER) pathway 9 . Impaired DNA repair impacts upon carcinogenesis and response to DNA damaging radiotherapy and chemotherapeutics 10 . Po...

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The Prognostic and Predictive Significance of PARP-1 in Locally Advanced Breast Cancer of Egyptian Patients Receiving Neoadjuvant Chemotherapy

Abstract: PARP-1 immunohistochemical expression is a marker of good prognosis and is predictive of response to NCT in LABC.

Cited by 9 publications

References 44 publications

Prognostic and clinicopathological value of poly (adenosine diphosphate-ribose) polymerase expression in breast cancer: A meta-analysis

Prognostic and clinicopathological value of poly (adenosine diphosphate-ribose) polymerase expression in breast cancer: A meta-analysis

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy

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