Biomarker assessment and molecular testing for prognostication in breast cancer

Kos, Zuzana; Dabbs, David J.

doi:10.1111/his.12795

Cited by 60 publications

(55 citation statements)

References 135 publications

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“…Patient prognosis is determined largely by stratification based on age, lymph node involvement, tumor grade, and tumor cell-surface expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (2)(3)(4)(5)(6)(7). Early diagnosis and targeted therapies, both hormonal and immunologic, are critical for the effective treatment of ER-, PR-, and HER2-positive disease.…”

Section: Introductionmentioning

confidence: 99%

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Taylor¹,

Vick²,

Iglesia³

et al. 2017

Journal of Clinical Investigation

131

105

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Section: Introductionmentioning

confidence: 99%

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Taylor¹,

Vick²,

Iglesia³

et al. 2017

Journal of Clinical Investigation

131

105

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“…Molecular imaging has been considered to exert a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments [13]. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumors for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set [14]. ER-targeted endocrine therapies are effective for the treatment of patients with ER-positive breast tumors and tamoxifen is the most widely used endocrine anti-estrogen treatment.…”

Section: Introductionmentioning

confidence: 99%

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

Giaginis

Sampani

Kotta-Loizou

et al. 2017

Pathol. Oncol. Res.

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Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.

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“…In particular, HER2 is implicated in the pathogenic mechanisms of certain types of breast cancer by promoting cell growth and survival89. Owing to their critical role in breast cancer, HER2 has become an important biomarker and target of anticancer therapy for breast cancer patients51011. In 2009, Pertuzumab was developed by Genentech for the treatment of HER2-positive breast cancer121314.…”

mentioning

confidence: 99%

Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties

Luo

Chen

et al. 2017

Sci Rep

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Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies. This study focused on the pharmacokinetic and pharmacodynamic properties of pertuzumab after glycoengineering. Herein, nonfucosylated pertuzumab was produced in CHOFUT8−/− cells, and desialylated pertuzumab was generated by enzymatic hydrolysis. Present data indicated that fucose was critical for ADCC activity by influencing the interaction between pertuzumab and FcγRIIIa, nevertheless removal of sialic acid increased the ADCC and CDC activity of pertuzumab. Meanwhile, regarding to sialic acid, sialidase hydrolysis directly resulted in asialoglycoprotein receptors (ASGPRs) dependent clearance in hepatic cells in vitro. The pharmacokinetic assay revealed that co-injection of asialofetuin can protect desialylated pertuzumab against ASGPRs-mediated clearance. Taken together, the present study elucidated the importance of fucose and sialic acid for pertuzumab, and also provided further understanding of the relationship of glycosylation/pharmacokinetics/pharmacodynamics of therapeutic antibody.

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Biomarker assessment and molecular testing for prognostication in breast cancer

Cited by 60 publications

References 135 publications

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties

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