Dataset Information

Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.

ABSTRACT:

Background

The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.

Methods

Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared test. Logistic regression was used for identification of predictive factors. The log-rank testing was utilized with disease-specific survival (DSS) and overall survival (OS) as the primary outcomes.

Results

A total of 23 270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis.

Conclusion

Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC.

SUBMITTER: Li Y

PROVIDER: S-EPMC6997059 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.

Li Yaming Y Su Peng P Wang Yifei Y Zhang Hanwen H Liang Yiran Y Zhang Ning N Song Xiaojin X Li Xiaoyan X Li Jie J Yang Qifeng Q Yang Qifeng Q

Cancer medicine 20191209 3

<h4>Background</h4>The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.<h4>Methods</h4>Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared t ...[more]

PMID: 31814295

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Project description:Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKC?/?, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKC?/? signaling as a potential therapeutic target for TNBC. Our observations indicated that PKC?/? signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKC?/? expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKC?/? significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKC?/?-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGF? and IL1? could activate PKC?/? signaling in TNBC cells and depletion of PKC?/? impairs NF-?B p65 (RelA) nuclear localization. We observed that cytokine-PKC?/?-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKC?/? promote TNBC growth, invasion and metastasis. Thus, targeting PKC?/? signaling could be a therapeutic option for breast cancer, including the TNBC subtype.

Dataset Information

Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.

Background

Methods

Results

Conclusion

Publications

Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.

Similar Datasets

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