Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets

Zhigang Chen (), Yi Zhang, Wenlu Li, Chenyi Gao, Fengbo Huang, Lu Cheng, Menglei Jin, Xiaoming Xu and Jian Huang ()
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Zhigang Chen: Zhejiang University School of Medicine
Yi Zhang: Zhejiang University School of Medicine
Wenlu Li: Massachusetts General Hospital, Harvard Medical School
Chenyi Gao: Zhejiang University School of Medicine
Fengbo Huang: Zhejiang University School of Medicine
Lu Cheng: Zhejiang University School of Medicine
Menglei Jin: Zhejiang University School of Medicine
Xiaoming Xu: Zhejiang University School of Medicine
Jian Huang: Zhejiang University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.

Date: 2023
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DOI: 10.1038/s41467-023-39059-3

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