Inference of tissue relative proportions of the breast epithelial cell types luminal progenitor, basal, and luminal mature

Hormone receptor negative breast cancers are highly aggressive, and are thought to originate from a subtype of epithelial cells called the luminal progenitor. In this paper, we show how to quantify the number of luminal progenitor cells as well as other epithelial subtypes in breast tissue samples using DNA and RNA based measurements. We find elevated levels of these hormone receptor negative luminal progenitor cells in breast tumour biopsies of hormone receptor negative cancers, as well as in healthy breast tissue samples from BRCA1 (FANCS) mutation carriers. We also find that breast tumours from carriers of heterozygous mutations in non-BRCA Fanconi Anaemia pathway genes are much more likely to be hormone receptor negative.

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Inference of tissue relative proportions of the breast epithelial cell types luminal progenitor, basal, and luminal mature

Scientific Reports ◽

10.1038/s41598-021-03161-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thomas E. Bartlett ◽

Peiwen Jia ◽

Swati Chandna ◽

Sandipan Roy

Keyword(s):

Single Cell ◽

Hormone Receptor ◽

Breast Tissue ◽

Single Cell Analysis ◽

Fanconi Anaemia ◽

Cell Analysis ◽

Breast Cancers ◽

Luminal Progenitor ◽

Tissue Samples ◽

Luminal Progenitor Cells

AbstractSingle-cell analysis has revolutionised genomic science in recent years. However, due to cost and other practical considerations, single-cell analyses are impossible for studies based on medium or large patient cohorts. For example, a single-cell analysis usually costs thousands of euros for one tissue sample from one volunteer, meaning that typical studies using single-cell analyses are based on very few individuals. While single-cell genomic data can be used to examine the phenotype of individual cells, cell-type deconvolution methods are required to track the quantities of these cells in bulk-tissue genomic data. Hormone receptor negative breast cancers are highly aggressive, and are thought to originate from a subtype of epithelial cells called the luminal progenitor. In this paper, we show how to quantify the number of luminal progenitor cells as well as other epithelial subtypes in breast tissue samples using DNA and RNA based measurements. We find elevated levels of cells which resemble these hormone receptor negative luminal progenitor cells in breast tumour biopsies of hormone receptor negative cancers, as well as in healthy breast tissue samples from BRCA1 (FANCS) mutation carriers. We also find that breast tumours from carriers of heterozygous mutations in non-BRCA Fanconi Anaemia pathway genes are much more likely to be hormone receptor negative. These findings have implications for understanding hormone receptor negative breast cancers, and for breast cancer screening in carriers of heterozygous mutations of Fanconi Anaemia pathway genes.

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

Journal of Personalized Medicine ◽

10.3390/jpm11050387 ◽

2021 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Giacomo Santandrea ◽

Chiara Bellarosa ◽

Dino Gibertoni ◽

Maria C. Cucchi ◽

Alejandro M. Sanchez ◽

...

Keyword(s):

Hormone Receptor ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Receptor Expression ◽

Hormonal Stimulation ◽

Tissue Samples ◽

Hormonal Receptor ◽

Hormone Receptor Expression ◽

Cystic Disease Fluid Protein

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

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