Triple‑negative breast cancer and its?association with obesity (Review)

Zou, Jing; Chen, Ling; Zu, Xuyu; Wen, Ge; Zhong, Jing

doi:10.3892/mco.2017.1429

Cited by 47 publications

(57 citation statements)

References 103 publications

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“…Importantly, obesity contributes to 20% of cancer-related deaths, with a higher incidence of breast cancer in obese individuals. Epidemiological studies reveal that the risk of triple-negative breast cancer (TNBC) is associated with an increase in Body Mass Index (BMI) and that a higher proportion of obese patients suffered from TNBC [2][3][4][5][6][7][8] . Furthermore, individuals with a high BMI have increased rates of metastasis and decreased response to chemotherapy 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Epidemiological studies reveal that the risk of triple-negative breast cancer (TNBC) is associated with an increase in Body Mass Index (BMI) and that a higher proportion of obese patients suffered from TNBC [2][3][4][5][6][7][8] . Furthermore, individuals with a high BMI have increased rates of metastasis and decreased response to chemotherapy 6 . TNBC, which represents approximately 25% of breast cancer cases, remains extremely hard to treat, due to its heterogeneous nature and the lack of driver mutations which can be directly targeted 9 .…”

Section: Introductionmentioning

confidence: 99%

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Obesity-driven changes in ECM composition promote local invasion and metastasis of breast tumors

Wishart

Peng

Conner

et al. 2020

Preprint

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The extracellular matrix (ECM) is a major component of the tumor microenvironment that supports cellular growth, promotes local invasion from the primary tumor, and contributes to metastatic outgrowth in sites of colonization. Obesity is a systemic disease that causes chronic inflammation which can lead to ECM deposition and ultimately fibrosis in adipose tissues such as the mammary gland. Overweight breast cancer patients have increased metastasis to the lung and liver, exhibit resistance to chemotherapy and have worse outcomes. We found that ECM isolated from the mammary gland of both tumor-bearing and obese mice increased invasion of breast cancer cells and set out to investigate whether obesity-driven changes in ECM could identify novel drivers of invasion and metastasis in breast cancer. We performed proteomics of the mammary fat pads of both lean and obese mice and identified the entire landscape of obesity-driven ECM changes. In particular, we focused on Collagen VI, an ECM protein secreted by adipocytes in mammary tissues. Collagen VI is upregulated in the ECM of obese and tumor-bearing mice and is associated with poor outcome in human breast cancer. We found that Collagen VI drives adhesion, migration and invasion of several human breast cancer cell lines via crosstalk between the adhesion receptor NG2 and the receptor tyrosine kinase EGFR, and activation of MAPK signaling. Overall, these studies demonstrate that obesity can have profound effects on the ECM composition of tissues, which in turn can promote local invasion and metastasis. these studies provide a novel mechanism by which obesity contributes to tumor progression and metastasis. Methods

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Obesity-driven changes in ECM composition promote local invasion and metastasis of breast tumors

Wishart

Peng

Conner

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, using the NCBI Phenotype-Genotype Integrator (https://www.ncbi.nlm.nih.gov/gap/phegeni), an intergenic variant in the MIR4311/DIS3L region (rs6494560) was associated with obesity (4.917 x 10-6), waist circumference (4.798 x 10-5), and body mass index (4.863 x 10-5) in the Family Heart Study genome wide association study [42]. Obesity is a known risk factor for TNBC [43], and there is some evidence that overweight or obesity is related to TNBC progression [44].…”

Section: Plos Onementioning

confidence: 99%

CLCA2 expression is associated with survival among African American women with triple negative breast cancer

et al. 2020

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“…36,41 Obesity activates tissue inflammatory responses, activating cancer cell survival, proliferation, and metastasis, 41 which introduces a plethora of potential targets in TNBC research. [42][43][44][45] Because activation of this pathway has higher incidence in Black patients, agents targeting the obesity/inflammation axis can be a potential strategy to treat certain patients in this cohort. The introduction of PDX models into preclinical drug testing facilitated a translational tool to evaluate single and combination drug therapies in the laboratory setting to test these candidate targets, mimicking clinical trials.…”

Section: Utilizing Tnbc Pdx Models To Identify Genes and Signaling Pamentioning

confidence: 99%

Patient-Derived Xenografts as an Innovative Surrogate Tumor Model for the Investigation of Health Disparities in Triple Negative Breast Cancer

Matossian

Giardina

Wright

et al. 2020

Women's Health Reports

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Despite a decline in overall incidence rates for cancer in the past decade, due in part to impressive advancements in both diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer-related deaths in women. BC alone accounts for *30% of all new cancer diagnoses in women worldwide. Triple-negative BC (TNBC), defined as having no expression of the estrogen or progesterone receptors and no amplification of the HER2 receptor, is a subtype of BC that does not benefit from the use of estrogen receptor-targeting or HER2-targeting therapies. Differences in socioeconomic factors and cell intrinsic and extrinsic characteristics have been demonstrated in Black and White TNBC patient tumors. The emergence of patient-derived xenograft (PDX) models as a surrogate, translational, and functional representation of the patient with TNBC has led to the advances in drug discovery and testing of novel targeted approaches and combination therapies. However, current established TNBC PDX models fail to represent the diverse patient population and, most importantly, the specific ethnic patient populations that have higher rates of incidence and mortality. The primary aim of this review is to emphasize the importance of using clinically relevant translatable tumor models that reflect TNBC human tumor biology and heterogeneity in high-risk patient populations. The focus is to highlight the complexity of BC as it specifically relates to the management of TNBC in Black women. We discuss the importance of utilizing PDX models to study the extracellular matrix (ECM), and the distinct differences in ECM composition and biophysical properties in Black and White women. Finally, we demonstrate the crucial importance of PDX models toward novel drug discovery in this patient population.

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Triple‑negative breast cancer and its?association with obesity (Review)

Cited by 47 publications

References 103 publications

Obesity-driven changes in ECM composition promote local invasion and metastasis of breast tumors

Obesity-driven changes in ECM composition promote local invasion and metastasis of breast tumors

CLCA2 expression is associated with survival among African American women with triple negative breast cancer

Patient-Derived Xenografts as an Innovative Surrogate Tumor Model for the Investigation of Health Disparities in Triple Negative Breast Cancer

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