The Clinical Significance of PR, ER, NF-<i>κ</i>B, and TNF-<i>α</i>in Breast Cancer

Zhou, Xianlong; Fan, Wei; Yang, Guowei; Mu, Yu

doi:10.1155/2014/494581

Cited by 44 publications

(34 citation statements)

References 30 publications

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“…Both ER and PR status correlated significantly with the stage of the disease, thereby indicating that ER, PR positive tumors were associated with early stage breast tumors. Similar correlation was also found in other studies (Zhou et al, 2014).…”

Section: Discussionsupporting

confidence: 92%

Clinico-Morphological Profile and Receptor Status in Breast Cancer Patients in a South Indian Institution

Ghosh

Sarkar²,

Simhareddy³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Breast cancer is the most common malignancy in women worldwide and the second most common cancer in females in India. Receptor status may be important for survival. Objective: To analyse and correlate the clinical and morphological parameters with receptor status in breast carcinoma patients in a tertiary care institution in Southern India. Materials and Methods: This retrospective study involved 320 patients of breast cancer diagnosed in an oncology hospital over a period of 3½ years. Data was analysed using SPSS Version 21. Results: Some 60.6% patients with breast carcinomas belonged to the age group of 40 to 60 years. The most common histological type was infiltrating ductal carcinoma, not otherwise specified, accounting for 84.4% of patients. On immunohistochemistry, estrogen receptor (ER) and progesterone receptor (PR) were expressed in 56.3% and 53.1% of cases, respectively. Conclusions: Breast cancers in India, a developing country, occur in younger women and tend to be more aggressive with lower rates of ER and PR expression and higher histological tumor grades. Both ER and PR status of the tumors had significant associations with the patient age, pathological TNM stage and histological tumor grade.

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Section: Discussionsupporting

confidence: 92%

Clinico-Morphological Profile and Receptor Status in Breast Cancer Patients in a South Indian Institution

Ghosh

Sarkar²,

Simhareddy³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Following the assessment of the role of NF-κB expression in breast tumor samples, one study showed that the frequency of p65 expression is higher in tumor cells of HER2 and basal-like subtypes compared to its expression in luminal A subtype cancer cells [58]. Another study, however, reported an association between ER and NF-κB expression, where the NF-κB expression correlates with higher tumor grade, stage III-IV, and lymph node metastasis [59]. Furthermore, Oida et al reported that NF-κB participated in the tamoxifen resistance in breast cancer cell line [60].…”

Section: Discussionmentioning

confidence: 99%

MAP3K1 Expression is Associated With Progression and Poor Prognosis of Hormone Receptor-Positive, HER2-Negative Early-Stage Breast Cancer

Kuo

Wei

Lee

et al. 2020

Preprint

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Background: MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) participates in the MAPK signal transduction pathway, responding to a number of mitogenic and metabolic stimuli, which may be related to breast cancer susceptibility and progression. In this study, we assessed whether overexpression of MAP3K1 promotes proliferation, migration, and invasion of breast cancer cells, and thus, affects the prognosis of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer. Methods: Two HR-positive, HER2-negative breast cancer cell lines (MCF7 and T-47D), both overexpressing MAP3K1, were transfected with MAP3K1 short hairpin RNA plasmids (shMAP3K1) and their proliferation, migration, and invasion were examined. We assessed whether shMAP3K1 affects the cell cycle and levels of downstream signaling molecules, such as ERK and NF-κB, as well as sensitizes cells in both cell lines to chemotherapeutic and hormonal agents. A total of 161 patients with HR-positive, HER2-negative T1-T2 breast cancer and 0 to 3 nodal metastases were included. The expression of MAP3K1 and phospho (p)-ERK proteins was assessed by immunohistochemistry. Results: In both cell lines (MCF7 and T-47D), shMAP3K1 significantly reduced cell growth, migration, and invasion by downregulating MMP-9 and blocking the G2/M phase of the cell cycle and its regulatory molecule cyclin B1. Besides, shMAP3K1 downregulated ERK- and NF-κB-dependent gene transcription, and enhanced sensitivities of both cell lines to doxorubicin, docetaxel, and tamoxifen. Patients with MAP3K1 overexpression exhibited significantly poor 9-year disease-free survival (DFS; 72.6% vs. 88.5%, p = 0.022) and overall survival (OS; 83.8% vs. 96.2%, p = 0.012) relative to those without MAP3K1 overexpression. Furthermore, the p-ERK expression was significantly associated with MAP3K1 expression (p < 0.001) and correlated with a poor 9-year DFS (p = 0.033) and OS (p = 0.023). Conclusions: Our results indicate that overexpression of MAP3K1 plays a major role in poor prognosis of HR-positive, HER2-negative early-stage breast cancer.

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“…Thus, we analyzed the impacts of TME-driven stimuli on the responses of CCR7-expressing luminal-A breast tumor cells to CCL21 chemotactic gradients in vitro and in vivo. The TME stimulus was induced by simultaneous exposure of luminal-A breast tumor cells to representatives of 3 relevant arms of the TME: 1) estrogen, the key hormonal factor in luminal-A tumors, which by definition, all express ER [18,19]; 2) TNF-a, a representative of the inflammatory arm; this cytokine has direct tumor-promoting effects in breast cancer and is expressed by ;90% of breast cancer patients with recurrent disease, including ER+ breast tumors [39][40][41][42][43]; and 3) EGF, a growth-stimulating factor that prevails in breast tumors [44,45]. Luminal-A tumors express EGFR and are characterized by high levels of ErbB3 [46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Weitzenfeld

Kossover

Körner

et al. 2016

Journal of Leukocyte Biology

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Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype.

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The Clinical Significance of PR, ER, NF-κB, and TNF-αin Breast Cancer

Cited by 44 publications

References 30 publications

Clinico-Morphological Profile and Receptor Status in Breast Cancer Patients in a South Indian Institution

Clinico-Morphological Profile and Receptor Status in Breast Cancer Patients in a South Indian Institution

MAP3K1 Expression is Associated With Progression and Poor Prognosis of Hormone Receptor-Positive, HER2-Negative Early-Stage Breast Cancer

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

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