“This important new information about DCIS biology and behavior could change the way we manage and treat the condition in the future,” says pathologist and lead investigator Jelle Wesseling from the Netherlands Cancer Institute. For example: radiotherapy to treat DCIS will not prevent an unrelated breast cancer later on in life. “Our findings bring us closer to understanding the risk of a particular DCIS lesion in a particular individual.”
Investigating the progression of DCIS to breast cancer is a methodologically challenging effort. The proportion of people with DCIS who later develop breast cancer is relatively small, and the disease occurs up to 20 years after the initial DCIS diagnosis. In the current study, the Cancer Grand Challenges team has overcome this obstacle by analyzing data and samples from well-annotated cohorts of people with DCIS from the Netherlands, the UK, and the US – which is the largest of its kind in the world.
The team integrated clinical, pathological, and epidemiological data from 95 women who developed breast cancer long after their DCIS, in addition to multiple layers of genomic, exomic, and mutational analyses up to the single-cell level. “This study is the culmination of a real tour de force,” says Jelle Wesseling.
A remaining question is why some people develop two clonally unrelated cancers in the same breast. One possibility might be that inherited genetic variants influence whether people are more likely to develop a recurrence or a new cancer after DCIS. Alternatively, certain factors in the breast microenvironment and surrounding tissue architecture might make some people more prone to breast tissue tumorigenesis, permitting the emergence of a second, unrelated primary tumor. Further research is ongoing to investigate these hypotheses.
Learn more about this and other Cancer Grand Challenges in the 2022 CGC annual progress magazine Discover, featuring NKI researchers Jelle Wesseling, Esther Lips, Jacco van Rheenen and Jos Jonkers.
The Cancer Grand Challenges PRECISION team is generously supported by Cancer Research UK and the Dutch Cancer Society.