The prognostic value of lymph node status among breast cancer subtypes

Liao, Guo‐Shiou; Chou, Yu-Ching; Hsu, Huan-Ming; Dai, Ming‐Shen; Yu, Jyh‐Cherng

doi:10.1016/j.amjsurg.2014.05.029

Cited by 28 publications

(24 citation statements)

References 32 publications

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“…This result was in accordance with other studies [20–22]. It is well known that in breast cancer, the number of positive lymph nodes is inversely associated with prognosis and survival.…”

Section: Discussionsupporting

confidence: 93%

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database

Wang

Jiang

et al. 2016

Oncotarget

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Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis. Data from the Surveillance, Epidemiology and End Results database (2010–2012) were used to identify 10,771 patients with TNBC, and we assessed the effects of lymph node (LN) status on breast cancer-specific survival (BCSS) and overall survival (OS). In our study, a Kaplan-Meier plot showed that LN-negative patients (N0) had better survival outcomes than LN-positive patients and that patients with ≥10 positive LNs (N3) exhibited the worst survival outcomes regardless of tumor size. A pairwise comparison showed no difference in survival outcomes among each group stratified by tumor size. Further, for LN-positive patients with a tumor size ≤2 cm (T1) or >5 cm (T3), there were similar outcomes between patients with one to three LNs (N1) and those with four to nine LNs (N2), whereas N1 patients experienced significantly better survival outcomes than N3 patients (P<0.001). Therefore, ten metastatic lymph nodes was the cut-off value for poor prognosis. Nevertheless, for patients with a tumor size of 2-5 cm (T2), the extent of LN involvement contributed prognostic value to OS but not BCSS. In summary, we found that nodal status and tumor size exhibited distinct interaction patterns for predicting the outcomes of TNBC. These results provide deeper insight into the prognostic value of nodal status in TNBC.

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“…This result was in accordance with other studies [20–22]. It is well known that in breast cancer, the number of positive lymph nodes is inversely associated with prognosis and survival.…”

Section: Discussionsupporting

confidence: 93%

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database

Wang

Jiang

et al. 2016

Oncotarget

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“…In general, the frequency of patients with LN metastasis is lower in the luminal-A subtype than in other disease subtypes. This is particularly so when luminal-A tumors are compared with the luminal-B subtype that shares several molecular characteristics with it [20][21][22][23][24][25][26]. In contrast, bone metastases are prevalent in luminal-A patients more than in other subtypes, and bones are the preferred metastatic site in this subtype of disease [23,26,27].…”

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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“…Breast cancers are classified depending on cell receptors; triple negative breast cancer (estrogen, progesterone and Her-2 receptor, TNBC) accounts for about 15–25% of all breast cancers 2 and is known to have the worst prognosis. 3–5 TNBC is more prevalent among low socioeconomic groups, especially Latino and African-American. 6, 7 …”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-Hyaluronan Conjugated Super-Paramagnetic Iron Oxide Nanoparticles (DOX-HA-SPION) Enhanced Cytoplasmic Uptake of Doxorubicin and Modulated Apoptosis, IL-6 Release and NF-kappaB Activity in Human MDA-MB-231 Breast Cancer Cells

Vyas¹,

Lopez-Hisijos²,

Gandhi³

et al. 2015

j nanosci nanotechnol

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Triple negative breast cancer exhibit increased IL-6 expression compared with matched healthy breast tissue and a strong link between inflammation and cancer progression and metastasis has been reported. We investigated whether doxorubicin-hyaluronan-super-paramagnetic iron oxide nanoparticles (DOX-HA-SPION) would show greater therapeutic efficacy in human triple negative breast cancer cells (TNBC) MDA-MB-231, as was recently shown in drug-sensitive and multidrug-resistant ovarian cancer cells. Therefore, we measured cellular DOX uptake via confocal microscopy; observed morphologic changes: mitochondrial and nuclear changes with electron microscopy, and quantitated apoptosis using FACS analysis after Annexin V and PI staining in MDA-MB-231 cells treated with either DOX alone or DOX-HA-SPION. We also measured both proinflammatory and anti-inflammatory cytokines; IL-6, IL-10 respectively and also measured nitrate levels in the conditioned medium by ELISA. Inaddition, NF-kB activity was measured by luciferase assay. Confocal microscopy demonstrated greater cytoplasmic uptake of DOX-HA-SPION than free DOX. We also demonstrated reduction of Vimentin with DOX-HA-SPION which is significantly less than both control and DOX. DOX-HA-SPION enhanced apoptosis and significantly down regulated both pro-inflammatory mediators IL-6 and NF-kB in comparison to DOX alone. The secretion levels of anti-inflammatory mediators IL-10 and nitrate was not decreased in the DOX or DOX-HA-SPION treatment groups. Our data suggest that DOX-HA-SPION nanomedicine-based drug delivery could have promising potential in treating metastasized and chemoresistant breast cancer by enhancing the drug efficacy and minimizing off-target effects.

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The prognostic value of lymph node status among breast cancer subtypes

Cited by 28 publications

References 32 publications

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database

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

Doxorubicin-Hyaluronan Conjugated Super-Paramagnetic Iron Oxide Nanoparticles (DOX-HA-SPION) Enhanced Cytoplasmic Uptake of Doxorubicin and Modulated Apoptosis, IL-6 Release and NF-kappaB Activity in Human MDA-MB-231 Breast Cancer Cells

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