Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study

Santandrea, Giacomo; Bellarosa, Chiara; Gibertoni, Dino; Cucchi, M.C.; Sánchez, Alejandro Martín; Franceschini, Gianluca; Masetti, Riccardo; Foschini, Maria Pia

doi:10.3390/jpm11050387

Cited by 6 publications

(5 citation statements)

References 29 publications

(36 reference statements)

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“…Higher ER expression was observed in the TDLU epithelium of samples from mature parous women compared to young nulliparous. Gradually increasing ER status has been previously reported in response to ageing (Santandrea et al, 2021; Shoker et al, 1999) and ER+ breast cancer is more common with increasing age (Shah et al, 2022). In turn, parity and the use of hormonal contraception have been shown to decrease ER levels (Russo et al, 1999; Williams et al, 1991; Hilton et al, 2018).…”

Section: Discussionmentioning

confidence: 96%

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Peurla

Paavolainen

Tammelin

et al. 2023

Preprint

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The major lactiferous ducts of the human breast branch out and ultimately end at terminal ductal lobular units (TDLUs). These glandular structures are the source of milk upon lactation, and also the most common origin of breast cancer. Despite their functional and clinical importance, the three dimensional (3D) architecture of TDLUs has remained undetermined, largely due to their absence in rodent animal models. By utilizing recent technological advances in optical tissue clearing and microscopy, we imaged the 3D structure of healthy human breast tissue to determine whether general branching patterns or cell type specific niches exist in the TDLU. Our data demonstrate that TDLUs have a consistent shape and their branch parameters are largely comparable between different TDLUs and individuals irrespective of age or parity. Simulation of TDLU branching morphogenesis in 3D by mathematical modelling suggests that evolutionarily conserved mechanisms regulate mammary gland branching in humans and mice, despite their anatomical differences. The data also demonstrate a new level of organization within the TDLU structure identifying a main branch that dominates in bifurcation events and exhibits a more duct-like keratin expression pattern. In all, our data provide the first structural insights into 3D human breast anatomy and branching, and exemplify the power of volumetric imaging in deeper understanding of human breast biology.

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Section: Discussionmentioning

confidence: 96%

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Peurla

Paavolainen

Tammelin

et al. 2023

Preprint

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“…Both proteins have previously been associated with younger age in normal breast tissue, although few studies have investigated the relationship. 41,43 Younger women have more mammographic breast density and respond to tamoxifen with a greater density decrease after therapy. 11,13 Progesterone is associated with greater overall mammographic density, in particular in younger and premenopausal women.…”

Section: Discussionmentioning

confidence: 99%

“…Greater epithelial proliferative activity and more stromal PR was predominantly found in younger and premenopausal women. Both proteins have previously been associated with younger age in normal breast tissue, although few studies have investigated the relationship 41,43 . Younger women have more mammographic breast density and respond to tamoxifen with a greater density decrease after therapy 11,13 .…”

Section: Discussionmentioning

confidence: 99%

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change

Gabrielson,

Hammarström,

Bergqvist

et al. 2024

Intl Journal of Cancer

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Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk‐reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen‐associated density change. This biopsy‐based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double‐blinded tamoxifen dose‐determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound‐guided core‐needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1–20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2‐fold higher PR expression compared to non‐responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen‐associated density decrease, and that the age‐associated difference in density change may be related to age‐dependant differences in expression of Ki67 and PR.

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“…37 ERα also acts as a key regulator of normal mammary gland development and differentiation, although knowledge remains limited regarding how hormone signaling is altered during the progression of luminal breast cancer. 38,39 The cell line MCF7 is hormone-dependent and is considered as a model of luminal breast cancer.…”

Section: Analysis Of Signaling Pathways In Breast Cancer Cells and Dr...mentioning

confidence: 99%

Design and synthesis of phosphoryl-substituted steroidal pyridazines (Pho-STPYRs) as potent estrogen receptor alpha inhibitors: targeted treatment of hormone-dependent breast cancer cells

Volkova,

Scherbakov,

Dzichenka

et al. 2024

RSC Med. Chem.

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Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study

Cited by 6 publications

References 29 publications

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change

Design and synthesis of phosphoryl-substituted steroidal pyridazines (Pho-STPYRs) as potent estrogen receptor alpha inhibitors: targeted treatment of hormone-dependent breast cancer cells

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