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The fourteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology and Breast Cancer was held on April 26th − 29th in Weggis, Switzerland. For the first time, early career researchers organised and took part in an additional ECR workshop on the 26th of April, which was received with great enthusiasm. The topics of the main workshop included mammary branching and morphogenesis, novel experimental systems (model organisms), systemic influences on tumour progression and the tumour microenvironment. Novel and recent findings were shared across excellent oral and poster presentations. [ABSTRACT FROM AUTHOR]

The thirteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) Laboratories Annual Workshop took place on the 28–30 April 2022 in Weggis, Switzerland and focused on methods in mammary gland biology and breast cancer. Sixty scientists participated in the ENBDC annual workshop which had not been held in person since 2019 due to the global COVID-19 pandemic. Topics spanned the mammary gland biology field, ranging from lactation biology and embryonic development, single cell sequencing of the human breast, and stunning cutting-edge imaging of the mouse mammary gland and human breast as well as breast cancer research topics including invasive progression of the pre-invasive DCIS stage, metabolic determinants of endocrine therapy resistance, models for lobular breast cancer, and how mutational landscapes of normal breast during age and pregnancy determine cancer risk. The latest findings from participating researchers were presented through oral presentations and poster sessions and included plenty of unpublished work. [ABSTRACT FROM AUTHOR]

A first full term birth at an early age protects women against breast cancer by reducing lifetime risk by up to 50%. The underlying mechanism resulting in this protective effect remains unclear, but many avenues have been investigated, including lobular differentiation, cell fate, and stromal composition. A single pregnancy at an early age protects women for 30-40 years and this long-term protection is likely regulated by a relatively stable yet still modifiable method, such as epigenetic reprogramming. Long lasting epigenetic modifications have been shown to be induced by pregnancy and to target the IGF pathway. Understanding how an early first full term pregnancy protects against breast cancer and the role of epigenetic reprogramming of the IGF system may aid in developing new preventative strategies for young healthy women in the future.

Lipids are released in milk as fat globules, which are droplets of apolar lipids surrounded by a complex membrane deriving from the mammary epithelial cell (MEC) and called the milk fat globule membrane (MFGM). The structure of the MFGM is highly complex and closely related to the mechanisms of milk fat globule secretion in the mammary epithelial cell. Indeed, MFGM is composed of two biological membranes, a phospholipid monolayer, deriving from the endoplasmic reticulum, and a phospholipid bilayer, which originates from the apical plasma membrane of the MEC, with variable amounts of cytoplasm trapped between. Biochemical techniques (i.e. sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by different staining procedures) have been employed historically to characterize major MFGM proteins, namely MUC-1, fatty acid synthase, xanthine oxidase, butyrophilin, lactadherin, and adipophilin. However, recent advances in the field of proteomics (mostly development of one-dimensional gel electrophoresis approach coupled with tandem mass spectrometry) have led to the identification of hundreds of proteins associated with the MFGM. Surprisingly, newly identified MFGM proteins were not only involved in lipid metabolic or exocytosis-related biological processes, but also in cell signalling, translation, or host defense-related mechanisms. Therefore, the milk fat globule should no longer be viewed as an inert structure only devoted to the delivery of lipids to the newborn, but rather as a dynamic and informative compartment which can contribute to the improvement of our comprehension of the mammary gland biology.

A first full-term birth at an early age protects women against breast cancer by reducing lifetime risk by up to 50%. The underlying mechanism resulting in this protective effect remains unclear, but many avenues have been investigated, including lobular differentiation, cell fate, and stromal composition. A single pregnancy at an early age protects women for 30-40 years, and this long-term protection is likely regulated by a relatively stable yet still modifiable method, such as epigenetic reprograming. Long-lasting epigenetic modifications have been shown to be induced by pregnancy and to target the IGF pathway. Understanding how an early first full-term pregnancy protects against breast cancer and the role of epigenetic reprograming of the IGF system may aid in developing new preventative strategies for young healthy women in the future. [ABSTRACT FROM AUTHOR]

Breast cancer incidence continues to increase in the US and Europe, a reflection of the growing influence of environment factors that interact with personal genetics. The US Environmental Protection Agency estimates that there are approximately 10,000 endocrine disrupting chemicals among the common daily exposures that could affect the risk of disease. The daunting tasks of identifying, characterizing, and elucidating the mechanisms of endocrine disrupting chemicals in breast cancer need to be addressed to produce a comprehensive model that will facilitate preventive strategies and public policy. An expert panel met to describe and bring attention to needs linking common environmental exposures, critical windows of exposure, and optimal times of assessment in investigating breast cancer risk. The group included investigators with extensive experience in the use of rodent models and in leading population studies and produced a set of recommendations for effective approaches to gaining insights into the environmental origins of breast cancer across the lifespan. [ABSTRACT FROM AUTHOR]

Lipids are released in milk as fat globules, which are droplets of apolar lipids surrounded by a complex membrane deriving from the mammary epithelial cell (MEC) and called the milk fat globule membrane (MFGM). The structure of the MFGM is highly complex and closely related to the mechanisms of milk fat globule secretion in the mammary epithelial cell. Indeed, MFGM is composed of two biological membranes, a phospholipid monolayer, deriving from the endoplasmic reticulum, and a phospholipid bilayer, which originates from the apical plasma membrane of the MEC, with variable amounts of cytoplasm trapped between. Biochemical techniques (i.e. sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by different staining procedures) have been employed historically to characterize major MFGM proteins, namely MUC-1, fatty acid synthase, xanthine oxidase, butyrophilin, lactadherin, and adipophilin. However, recent advances in the field of proteomics (mostly development of one-dimensional gel electrophoresis approach coupled with tandem mass spectrometry) have led to the identification of hundreds of proteins associated with the MFGM. Surprisingly, newly identified MFGM proteins were not only involved in lipid metabolic or exocytosis-related biological processes, but also in . cell signalling, translation, or host defense-related mechanisms. Therefore, the milk fat globule should no longer be viewed as an inert structure only devoted to the delivery of lipids to the newborn, but rather as a dynamic and informative compartment which can contribute to the improvement of our comprehension of the mammary gland biology. [ABSTRACT FROM AUTHOR]

The ovarian steroid hormones, estradiol and progesterone, and their nuclear receptors (estrogen receptor [ER] and progesterone receptor [PR]), are involved in breast cancer development. As ER-positive/PR-positive tumors progress, they are likely to become steroid hormone-resistant/independent, yet often retain expression of their steroid receptors. Notably, up to 40% of women with steroid receptor-positive tumors exhibit de novo resistance or eventually fail on estrogen- or ERa-blocking therapies (acquired resistance). Indeed, most of the research on this topic has centered on mechanisms of ER 'escape' from endocrine therapy and the design of better ER-blocking strategies; signaling pathways that mediate endocrine (i.e., anti-estrogen) resistance are also excellent therapeutic targets. However, serious consideration of PR isoforms as important drivers of early breast cancer progression and ER modulators is timely and significant. Indeed, progress has been hindered by ER-centric experimental approaches. This article will focus on defining a role for PR in breast cancer with hopes of providing a refreshing PR-focused perspective. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Bone-related diseases, such as osteoporosis and rheumatoid arthritis, affect hundreds of millions of people worldwide and pose a tremendous burden to health care. By deepening our understanding of the molecular mechanisms of bone metabolism and bone turnover, it became possible over the past years to devise new and promising strategies for treating such diseases. In particular, three tumor necrosis factor (TNF) family molecules, the receptor activator of NF-κB (RANK), its ligand RANKL, and the decoy receptor of RANKL, osteoprotegerin (OPG), have attracted the attention of scientists and pharmaceutical companies alike. Genetic experiments revolving around these molecules established their pivotal role as central regulators of osteoclast development and osteoclast function. RANK-RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also fine-tunes bone homeostasis both in normal physiology and disease. In addition, RANKL and RANK have essential roles in lymph node formation, establishment of the thymic microenvironment, and development of a lactating mammary gland during pregnancy. Consequently, novel drugs specifically targeting RANK, RANKL, and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various ailments associated with bone loss, such as arthritis, periodontal disease, cancer metastases, and osteoporosis. [ABSTRACT FROM AUTHOR]

Background/aim: GATA3, a transcription factor expressed in luminal breast epithelial cells, is required for mammary gland development. Heterozygous GATA3 mutations occur in up to 15% of estrogen receptor (ER)-positive breast tumors and have been proposed to be null alleles resulting in haploinsufficiency; however, the mutation spectrum of GATA3 in breast cancer is in sharp contrast to that found in HDR syndrome, a true GATA3 haploinsufficiency disease., Materials and Methods: Transgenic mice, 3D cultures and xenografts were used to examine the effect of mutant GATA3 expression on mammary cell proliferation., Results: Mutant GATA3 accelerated tumor growth of ZR751 cell xenografts and promoted precocious lobuloalveolar development in transgenic mouse mammary glands., Conclusion: GATA3 mutations, recently observed in breast cancer, encode active transcription factors, which elicit proliferative phenotypes in normal mammary epithelium and promote the growth of ER-positive breast cancer cell lines., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)