Rewiring of the Endocrine Network in Triple-Negative Breast Cancer

Abstract

The immunohistochemical definition of estrogen/progesterone receptors dictates endocrine feasibility in the treatment course of breast cancer. Characterized by the deficiency of estrogen receptor α, ERα-negative breast cancers are dissociated from any endocrine regimens in the routine clinical setting, triple-negative breast cancer in particular. However, the stereotype was challenged by triple-negative breast cancers’ retained sensitivity and vulnerability to endocrine agents. The interplay of hormone action and the carcinogenic signaling program previously underscored was gradually recognized along with the increasing investigation. In parallel, the overlooked endocrine-responsiveness in ERα-negative breast cancers attracted attention and supplied fresh insight into the therapeutic strategy in an ERα-independent manner. This review elaborates on the genomic and non-genomic steroid hormone actions and endocrine-related signals in triple-negative breast cancers attached to the hormone insensitivity label. We also shed light on the non-canonical mechanism detected in common hormone agents to showcase their pleiotropic effects.

CmPn signaling networks in the tumorigenesis of breast cancer

“…Ironically, recent data demonstrated that there is still quite a significant biological and/or clinical relevance of sex steroids in TNBCs and the action of these hormones is exerted through similar molecular mechanisms ( 10 – 14 ). This suggests a possible existence of previously undefined sex steroid receptor-mediated signaling pathways that retain the sensitivity and vulnerability of TNBCs to endocrine hormones ( 15 ), reemphasizing that perturbed expression of sex hormone receptors and abnormally long-exposure to sex steroids should be equally evaluated for more effective preventative strategies for breast cancers ( 16 , 17 ). Efforts on this aspect have thus far identified several candidate steroid receptors, including androgen receptors (ARs), novel classic ERs (ER-βs), and G-protein-coupled ERs (GPERs), in the pathobiological actions of sex hormones in TNBCs.…”

G-quadruplex DNA structures mediate non-autonomous instruction of breast tumour microenvironments

“…Arginase 1 is known to deplete arginine locally from the TME to suppress further other immune cells like T cells 49,50,51 . High expression of GR in breast cancer is linked to the development of TNBC and poor clinical outcome 52,53 . The pharmacological antagonism of GR-sensitised TNBC against DNA-damaging chemotherapy was indicated as a new therapeutic approach 54 .…”

Combined targeting of KRT23 and NCCRP1 as a potential novel therapeutic approach for the treatment of triple-negative breast cancer

“…Breast cancers characterized by triple-negative status tend to be more malignant and have a poorer prognosis (1,2,(4)(5)(6)19,20). To decrease the mortality rate and improve the prognosis of breast cancer patients, a model for predicting breast cancer risk should be developed.…”

“…Breast cancer with triple-negative receptors lacks the genes for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu. It accounts for 15–20% of all breast cancers and has a poor prognosis ( 1 , 2 ). In the absence of ER, PR, and HER2/neu, optimizing the therapeutic management of patients is difficult ( 2 , 3 ).…”