scholarly journals Interface between obesity with dysfunctional metabolism and inflammation, and the triple-negative breast cancer in African American women

Author(s):  
Katarzyna Rygiel

Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant “obese” tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the “obese” TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, “flexible” metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women.

2017 ◽  
Author(s):  
Aline S. Fonseca ◽  
Selene Elifio-Esposito ◽  
Marilesia F. Souza ◽  
Akanksha Mahajan ◽  
Yara R. Zabala ◽  
...  

2018 ◽  
Vol Volume 11 ◽  
pp. 1-12 ◽  
Author(s):  
Odalys Torres-Luquis ◽  
Krystal Madden ◽  
N'sanh MR N'dri ◽  
Richard Berg ◽  
Olufunmilayo F. Olopade ◽  
...  

2021 ◽  
Author(s):  
Johnathan Abou-Fadel ◽  
Brian Grajeda ◽  
Xiaoting Jiang ◽  
Alyssa-Marie Cailing-De La O ◽  
Esmeralda Flores ◽  
...  

Breast cancer is the most commonly diagnosed cancer worldwide and remains the second leading cause of cancer death. While breast cancer mortality has steadily declined over the past decades through medical advances, an alarming disparity in breast cancer mortality has emerged between African American women (AAW) and Caucasian American women (CAW); and new evidence suggests more aggressive behavior of triple-negative breast cancer (TNBC) in AAW may contribute to racial differences in tumor biology and mortality. Progesterone (PRG) is capable of exerting its cellular effects through either its classic, non-classic or combined responses through binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs), warranting both pathways an equally important status in PRG-mediated signaling. In our previous report, we demonstrated that the CCM signaling complex (CSC) consisting of CCM1, CCM2, and CCM3 proteins can couple both nPRs and mPRs signaling cascades to form a CSC-mPRs-PRG-nPRs (CmPn) signaling network in nPR positive(+) breast cancer cells. In this report, we furthered our research by establishing the CSC-mPRs-PRG (CmP) signaling network in nPR(-) breast cancer cells, demonstrating that a common core mechanism exists, regardless of nPR(+/-) cell type. This is the first report stating that inducible expression patterns exist between CCMs and major mPRs in TNBC cells. Furthermore, we firstly show mPRs in TNBC cells are localized in the nucleus and participate in nucleocytoplasmic shuttling in a coordinately synchronized fashion with CCM proteins under steroid actions, following the same cellular distribution as other well-defined steroid hormone receptors. Finally, for the first time, we deconvoluted the CmP signalosome by using multi-omics approaches, which helped us understand key factors within the CmP network, and identify 21 specific biomarkers with potential clinical applications associated with AAW-TNBC tumorigenesis. These novel biomarkers could have immediate clinical implications to dramatically improve health disparities among AAW-TNBCs.


2021 ◽  
Author(s):  
Mary Roselin Nittala ◽  
Satyaseelan Packianathan ◽  
Gary L. Shultz ◽  
Paul Roberts ◽  
Eswar K. Mundra ◽  
...  

Abstract Background Triple negative breast cancer (TNBC) (estrogen receptor (ER) – negative, progesterone receptor (PR) - negative, and human epidermal growth factor receptor 2 (HER2) -negative) is an aggressive subtype of breast cancer that is more common in younger women, carries a poorer prognosis and has a greater metastatic potential than receptor positive subtypes. Radiation therapy’s ability to improve outcomes, especially the overall survival is controversial, more so among African American patients. The objective of this study is to evaluate local control and survival rates of TNBC patients treated with radiotherapy (RT) in our institution with a sizeable cohort of African American women. Methods This is a retrospective analysis of 67 TNBCs (2007–2017) at an academic state institution who underwent a lumpectomy and /or mastectomy (surgery) followed by adjuvant irradiation to a median total dose of 50 Gy (range 40.5–50.40 Gy). Chemotherapy was administered in a neoadjuvant (32) or adjuvant setting (35). For all 67 TNBCs, local control (LC), overall survival (OS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The significance of survival variables was analyzed using the Cox univariate and multivariate proportional hazards model. A p-value of less than 0.05 was considered statistically significant. The SPSS 24.0 software was used for data analysis. Results The baseline characteristics of all 67 TNBCs were measured with median follow up of 58 months (range 10–142 months). Patients were stratified into two groups (neoadjuvant chemotherapy-RT (32) vs. adjuvant chemotherapy-RT (35)). The five-year rates for LC, DFS and OS were 14.8 % vs. 47.9 % (p = 0.002), 24.2% vs. 53.1 % (p = 0.015), and 65.1% vs. 92.2% (0.002) respectively. On Cox multivariate analysis, patients who received adjuvant chemotherapy were associated with statistically improved significant LC (p = 0.002) and OS (p = 0.002). The variables included were: BMI (p = 0.050), distance travelled (p = 0.027), 8th AJCC TNM staging (p = 0.018) and tumor grade (p = 0.022). Conclusion In this hypothesis-generating report, among TNBC patients undergoing RT, adjuvant chemotherapy appears to be better than neoadjuvant chemotherapy in determining the clinical outcomes.


2016 ◽  
Author(s):  
Julie E. Getz ◽  
Davyd B. Teoh ◽  
Sara Nasser ◽  
Christophe R. Legendre ◽  
Waibhav Tembe ◽  
...  

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