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A risk-associated Active transcriptome phenotype expressed by histologically normal human breast tissue and linked to a pro-tumorigenic adipocyte population.


ABSTRACT:

Background

Previous studies have identified and validated a risk-associated Active transcriptome phenotype commonly expressed in the cancer-adjacent and histologically normal epithelium, stroma, and adipose containing peritumor microenvironment of clinically established invasive breast cancers, conferring a 2.5- to 3-fold later risk of dying from recurrent breast cancer. Expression of this Active transcriptome phenotype has not yet been evaluated in normal breast tissue samples unassociated with any benign or malignant lesions; however, it has been associated with increased peritumor adipocyte composition.

Methods

Detailed histologic and transcriptomic (RNAseq) analyses were performed on normal breast biopsy samples from 151 healthy, parous, non-obese (mean BMI?=?29.60?±?7.92) women, ages 27-66 who donated core breast biopsy samples to the Komen Tissue Bank, and whose average breast cancer risk estimate (Gail score) at the time of biopsy (1.27?±?1.34) would not qualify them for endocrine prevention therapy.

Results

Full genome RNA sequencing (RNAseq) identified 52% (78/151) of these normal breast samples as expressing the Active breast phenotype. While Active signature genes were found to be most variably expressed in mammary adipocytes, donors with the Active phenotype had no difference in BMI but significantly higher Gail scores (1.46 vs. 1.18; p?=?0.007). Active breast samples possessed 1.6-fold more (~?80%) adipocyte nuclei, larger cross-sectional adipocyte areas (p?ConclusionsThe risk-associated Active transcriptome phenotype first identified in cancer-adjacent breast tissues also occurs commonly in healthy women without breast disease who do not qualify for breast cancer chemoprevention, and independently of breast expressed cancer-associated mutations. The risk-associated Active phenotype appears driven by a pro-tumorigenic adipocyte microenvironment that can predate breast cancer development.

SUBMITTER: Kang T 

PROVIDER: S-EPMC7395362 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A risk-associated Active transcriptome phenotype expressed by histologically normal human breast tissue and linked to a pro-tumorigenic adipocyte population.

Kang Taekyu T   Yau Christina C   Wong Christopher K CK   Sanborn John Z JZ   Newton Yulia Y   Vaske Charlie C   Benz Stephen C SC   Krings Gregor G   Camarda Roman R   Henry Jill E JE   Stuart Josh J   Powell Mark M   Benz Christopher C CC  

Breast cancer research : BCR 20200731 1


<h4>Background</h4>Previous studies have identified and validated a risk-associated Active transcriptome phenotype commonly expressed in the cancer-adjacent and histologically normal epithelium, stroma, and adipose containing peritumor microenvironment of clinically established invasive breast cancers, conferring a 2.5- to 3-fold later risk of dying from recurrent breast cancer. Expression of this Active transcriptome phenotype has not yet been evaluated in normal breast tissue samples unassocia  ...[more]

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