Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs

Sep 24, 2026

Uploaded by Stanley

Breast cancer research evaluates whether spontaneous mammary tumors in pet dogs can model human basal-like breast cancer (BLBC), a hard-to-treat, often triple-negative subtype. The study classifies 236 canine mammary tumors using RNA-seq–based subtyping, PAM50, and machine-learning feature genes, then compares dog and human subtype homology. Two canine subtypes emerge: one aligns molecularly with human BLBC, while the other does not; the canine BLBC-like group recapitulates key cell-cycle, TP53, interferon-γ, and Wnt-pluripotency features, with notable ER−PR+ variation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Human breast cancer heterogeneity

Rationale for pet dog models

Watson et al. Breast Cancer Research (2023) 25:114 [https://doi.org/10.1186/s13058-023-01705-5](https://doi.org/10.1186/s13058-023-01705-5) Breast Cancer Research RESEARCH Open Access Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs Joshua Watson1, Tianfang Wang2, Kun‑Lin Ho 1, Yuan Feng1, Tanakamol Mahawan3, Kevin K. Dobbin4 and Shaying Zhao1,2* Abstract Background About 20% of breast cancers in humans are basal‑like, a subtype that is often triple‑negative and dif‑ ficult to treat. An effective translational model for basal‑like breast cancer is currently lacking and urgently needed. To determine whether spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog–human molecular homology at the subtype level. Methods We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA‑seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We identified feature genes for human BLBC and luminal A subtypes via machine learning and used these genes to repeat canine‑alone and cross‑species tumor classifications. We inves‑ tigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog–human subtype comparison. Results Our independent genome‑wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal‑like and clusters with human BLBC in cross‑species PAM50 and feature gene classifications, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal‑like subtype recaptures key molecular features (e. g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched in histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal‑like tumors are estrogen receptor negative (ER−) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER−PR+ canine tumors harbor additional basal‑like features, including upregulation of genes of interferon‑γ response and ofthe Wnt‑pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors and with the expression ofT cell exhaustion markers (e. g., PDCD1) in ER−PR+ canine tumors. Conclusions We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall and thus could serve as a vital translational model of this devastating breast cancer subtype. Our study also shedslight on the dog–human difference in the mammary tumor histology and the hormonal cycle. *Correspondence: Shaying Zhao [szhao@uga.edu](szhao@uga.edu) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons

FAQs

What question does the study address about basal-like breast cancer models?

It tests whether spontaneous mammary tumors in pet dogs can serve as a translational model for human basal-like breast cancer by assessing subtype-level molecular homology.

How were the canine mammary tumors analyzed in this research?

The authors subtyped 236 canine mammary tumors using RNA-seq–based strategies and PAM50 classification, including analyses with and without human tumors combined.

What key finding links one canine subtype to human BLBC?

A molecularly distinct canine subtype consistently clusters with human BLBC in cross-species PAM50 and feature-gene classifications and recaptures hallmark BLBC molecular features.

Sep 24, 2026

Uploaded by Stanley