Unraveling the intricate molecular mechanisms of sex hormones' roles in breast cancer pathogenesis: A review.

Authors

Matthew Chibunna Igwe, Ogbonna Alphonsus Ogbuabor, Simeon Ikechukwu Egba

Published in

Medicine. Volume 105. Issue 26. Pages e49376. Jun 26, 2026.

Abstract

This study examines the role and function of the specific signaling molecules that are associated with the binding of sex hormone receptors, including estrogen receptor (ER) and progesterone receptor (PR), in relation to cell proliferation, differentiation, and survival. The present work focuses on the mutual relationship between signaling pathways of sex hormone receptors and MAPK and PI3K/AKT pathways, as well as the involvement of these molecules in the development of breast cancer. The review systemizes the present knowledge regarding genetic changes related to breast cancer, including the effects of changes on sex hormone signaling, biochemical pathways influencing sex hormone availability, and epigenetic modifications. The focus is made on genetic changes the researchers observed in breast cancer, like ERBB2/HER2 amplification and TP53 mutations, which cooperate with sex hormone signaling to advance tumor growth. The changes in the metabolism of sex hormones are as follows: High aromatase leading to high estrogen and more. Furthermore, the impact of sex steroids on the tumor microenvironment, including angiogenesis, immune regulation, and matrix, is consequently discussed. The effects of sex hormones on DNA methylation, histone modifications, and noncoding RNA with regard to breast cancer development are reviewed. The study also demonstrates how genetic changes, metabolism, and epigenetics work in concert with sex hormones to modulate breast cancer development. SERMs, aromatase inhibitors, and the endocrine approach are described, as well as novel directions to develop inhibitors of androgen and other hormone signaling pathways.

PMID:
42363452
Bibliographic data and abstract were imported from PubMed on 27 Jun 2026.

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