Cell changes around early breast cancers provide clues to why some cases become invasive

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by University of Texas MD Anderson Cancer Center

edited by Sadie Harley, reviewed by Robert Egan

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Representative image highlighting different microenvironment cell types surrounding the ducts with preinvasive breast cancer cells. Credit: Navin lab; The University of Texas MD Anderson Cancer Center

Researchers at The University of Texas MD Anderson Cancer Center have created one of the most detailed maps to date of the cell environment surrounding ductal carcinoma in situ (DCIS), the most common form of preinvasive, or stage 0, breast cancer. The findings may help explain why some lesions progress to invasive breast cancer and others do not, informing strategies to improve patient risk prediction and develop better targeted approaches for patients at higher risk of invasive disease.

The study, published in Science, was co-led by Nicholas Navin, Ph.D., chair of Systems Biology, and Savitri Krishnamurthy, M.D., professor of Anatomical Pathology, as well as co-first authors Siyuan He, Ph.D., and Aatish Thennavan, Ph.D., postdoctoral fellows of Systems Biology.

"DCIS is considered a snapshot before breast cancer becomes invasive, but not all DCIS cases progress to invasive disease, and the biology surrounding these lesions has been challenging to examine," Navin said.

"This atlas reveals the surrounding cells and structures that may help disease become invasive. In the future, these findings may allow clinicians to better identify and treat patients with DCIS who are at higher risk of invasive progression while also avoiding unnecessary treatments for those at low risk."

What is DCIS and what do we know about its tumor microenvironment?

DCIS occurs when abnormal cells grow inside the breast milk ducts but have not yet spread into surrounding tissue. It is considered to be a precursor to the most common type of breast cancer.

Mammograms and other breast examinations have increased the detection of DCIS cases, but many of these lesions never progress to invasive disease, making it challenging to determine which patients actually need more aggressive treatment.

While genetic changes in DCIS have been well studied, little is known about its tumor microenvironment—the community of immune cells, blood vessels and tissue cells that surround and interact with the cancer cells. This led the researchers to generate a comprehensive atlas for DCIS.

How did the researchers create this map and what did it show?

Using advanced single-cell and spatial profiling technologies, the researchers mapped more than 850,000 cells from samples of normal breast tissue, DCIS and invasive breast cancer. They identified extensive changes in cancer cells and the surrounding microenvironment as disease progressed. The detailed atlas suggests that important biological features associated with invasive breast cancer begin to emerge earlier than previously known.

The study also uncovered previously unknown "cancer stromal loops," ringlike structures made of supportive tissue and vascular cells that surround DCIS lesions, which create conditions that support tumor growth.

What does this mean for researchers and patients with breast cancer?

Additional research is needed to validate these findings and evaluate their potential use in future diagnostic tools and prevention or treatment strategies. Researchers will continue studying the cellular features identified in this atlas to determine whether they can predict which DCIS lesions are most likely to become invasive in order to better determine the best strategies for individual patients.

Publication details

Siyuan He et al., A cellular atlas of the preinvasive breast cancer microenvironment, Science (2026). DOI: 10.1126/science.aef4622. www.science.org/doi/10.1126/science.aef4622

Journal information: Science

Key medical concepts

Carcinoma, Intraductal, NoninfiltratingTumor MicroenvironmentInvasive Breast Carcinoma

Clinical categories

OncologyWomen's healthCommon illnesses & Prevention Provided by University of Texas MD Anderson Cancer Center Who's behind this story?

Sadie Harley

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