The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology.

/pdf/ki-67-as-a-prognostic-biomarker-in-invasive-breast-cancer-3yu7t1pup5.pdf

Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer

EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells.

Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information. They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease. Hence, detecting and characterizing CTCs can definitely become an inevitable step in treating solid tumor malignancies. In this review, we have tried to comprehend the basics of CTCs including isolation, detection, characterization, and molecular mechanism of their circulation in the blood stream. We have mostly focused on the significance of CTCs in diagnosis and therapies of four most common types of cancers, namely, breast, prostate, lung, and colorectal. This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

/pdf/role-of-circulating-tumor-cells-in-future-diagnosis-and-24fxe1dnuk.pdf

Role of circulating tumor cells in future diagnosis and therapy of cancer

Lung cancer is the second most common cancer and the main cause of cancer-related mortality worldwide. In spite of various efforts that have been made to facilitate the early diagnosis of lung cancer, most patients are diagnosed when the disease is already in stage IV, which is generally associated with the occurrence of distant metastases and a poor survival. Moreover, a large proportion of these patients will relapse after treatment, heralding the need for the stratification of lung cancer patients in addition to identifying those who are at a higher risk of relapse and, thus, require alternative and/or additional therapies. Recently, circulating tumor cells (CTCs) have been considered as valuable markers for the early diagnosis, prognosis and risk stratification of cancer patients, and they have been found to be able to predict the survival of patients with various types of cancer, including lung cancer. Additionally, the characterization of CTCs has recently provided fascinating insights into the heterogeneity of tumors, which may be instrumental for the development of novel targeted therapies. Here we review our current understanding of the significance of CTCs in lung cancer metastasis. We also discuss prominent studies reporting the utility of enumeration and characterization of CTCs in lung cancer patients as prognostic and pharmacodynamic biomarkers for those who are at a higher risk of metastasis and drug resistance.

Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer.

To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC.Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method.455 patients were included (267 EGFR-mutated, EGFR-M+; 188 EGFR-wildtype, wt). Median age at diagnosis was 65 years, 52.3% (238/455) of patients were males, 62.9% (286/455) of patients were never-smokers and 92.5% (421/455) of patients had R0 resection. Stage IA comprised 42.4% (193/455) of patients, Stage IB comprised 23.1% (105/455) of patients, Stage IIA comprised 10.8% of patients (49/455), Stage IIB comprised 5.1% of patients (23/455) and Stage IIIA comprised 18.7% (85/455) of patients. Among EGFR-M+, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-M+ and EGFR-wt was 45.3% (121/267) and 54.8% (103/188) respectively (p = 0.047). At median follow-up of 47 months, 178 patients had relapsed. Among EGFR-M+, 2-year DFS comparing PD-L1 <1% and PD-L1 ≥1% was 78.1% and 67.6% (p = 0.007) while 5-year OS was 59.5% and 42.8% (p = 0.001), respectively. Controlling for age, gender, lymphovascular invasion, adjuvant therapy and resection margin status, PD-L1 ≥1% (hazard ratio, HR 2.18, 95% CI 1.04-4.54, p = 0.038), stage IIB (HR 7.78, 95% CI 1.72-35.27, p = 0.008) and stage IIIA (HR 4.45, 95% CI 1.44-13.80, p = 0.01) emerged as independent predictors of inferior OS on multivariable analysis. In exploratory analysis, genomic analysis of 81 EGFR-M+ tumours was performed. PD-L1 ≥1% tumours had significantly higher rates of TP53 mutations (36.1% versus 15.6%, p = 0.04), with predominantly missense mutations.PD-L1 ≥1% is an independent predictor of worse OS among early-stage EGFR-mutated NSCLC and is associated with inferior DFS regardless of EGFR status. PD-L1 score as a risk stratification factor should be evaluated in prospective adjuvant studies among EGFR-mutated NSCLC. 

PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer.

Background: The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma (ADC) remains controversial The present study was aimed to clarify the role of PD-L1 expression in predicting prognosis and to investigate its biological function in ADC

Materials and Methods: The association between PD-L1 expression and clinical outcomes in patients with resected ADC was analyzed using immunohistochemistry (IHC) in our cohort (n=104), externally validated by a meta-analysis of 13 published studies The biological role of PD-L1 in ADC was explored using gene set enrichment analysis (GSEA)

Results: Positive PD-L1 expression in tumor cells was observed in 385% (40/104) High PD-L1 expression levels were significantly correlated with poor overall survival (P=0008) Furthermore, the meta-analysis also showed that positive PD-L1 expression was associated with shorter OS than negative PD-L1 expression (HR= 175, 95% CI: 126-242; P<0001) In subgroup analysis stratified according to ethnicity, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for Asian populations (HR= 211, 95% CI: 148-302; P<0001), but not for non-Asian populations (HR=116, 95% CI: 063-211, P=064) The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis (OR=174, 95% CI: 123-246; P=0002) and male (OR=156, 95% CI: 102-237; P=004) GSEA revealed PD-L1 expression levels positively correlated with immune process or immune-related pathways

Conclusion: PD-L1 expression is an important negative prognostic factor in resected ADC This finding has important implications for immunotherapy targeting the PD-1/PD-L1 pathway in patients with resected ADC

/pdf/prognostic-value-of-pd-l1-expression-in-resected-lung-1nbjzlxt4y.pdf

Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.

Circulating tumor cells (CTCs) are tumor cells that enter the blood circulation after detaching from the primary tumor and can migrate to reach distant organs, where they can give rise to aggressive metastasis. Clinical studies have revealed that the presence of CTCs in peripheral blood is correlated with disease progression in lung cancer. However, as CTCs are rare cancer cells released from tumors into the bloodstream, both enrichment and sensitive detection methods are technically challenging. In order to best understand how CTCs are currently being deployed, this review mainly focuses on the different detection methods for CTCs. Furthermore, we will describe the clinical impact of circulating tumor cells in lung cancer and discuss their potential use as biomarker to guide the prognosis.

/pdf/circulating-tumor-cells-in-lung-cancer-detection-methods-and-5brpnxw7ye.pdf

Circulating tumor cells in lung cancer: Detection methods and clinical impact*

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Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.

Circulating tumor cells in lung cancer: Detection methods and clinical impact*