New study using Hartwig Medical Foundation data maps how breast cancer’s genetic makeup shifts when it spreads

Analysis of nearly 1,300 tumor genomes across ten genomic subtypes points to candidate drug targets and biomarkers for metastatic breast cancer

14 July 2026 — Researchers at Cancer Research UK Cambridge Institute, have published a study in Scientific Reports describing how the genetic profile of breast cancer changes as it spreads to other organs, and how those changes differ depending on a tumor’s underlying genomic subtype. The work draws on nearly 1,300 whole-genome sequenced tumors, including 750 metastatic biopsies made available through the Hartwig Medical Database.

In 2012, Cambridge researchers led by Carlos Caldas [current affiliation HUJI – Hebrew University in Jerusalem | the Lautenberg Centre for Immunology and Cancer Research – Faculty of medicine] classified breast cancer into ten genomic subtypes, known as Integrative Clusters, based on patterns of DNA copy number changes — sections of the genome that are duplicated or lost. These subtypes carry markedly different risks of relapse. Until now, it has been unclear which genetic changes accompany the transition from primary tumor to metastatic disease within each subtype, since studies have typically been too small, lacked a primary-tumor comparison, or sequenced only a limited set of known cancer genes.

By comparing primary and metastatic tumor genomes subtype by subtype, the researchers found that metastases tend to be more genetically uniform than primary tumors, yet no less unstable. They also pinpointed specific genes and biological pathways — including DNA repair, hormone signaling, and pathways linked to resistance to HER2-targeted therapy — that are gained or lost more often once cancer has spread, with the pattern depending on genomic subtype. The subtypes also differed in where they tend to spread: one subtype was markedly under-represented among liver metastases, for example, while a largely HER2-positive subtype was over-represented in the lungs.

Potential impact for patients

For patients, the findings offer a roadmap towards more precisely matched treatment once breast cancer has spread — a stage of disease with far poorer outcomes than primary breast cancer. By linking genomic subtypes to specific vulnerabilities in metastases, such as DNA repair defects that could be targeted with PARP inhibitors, or growth-signaling changes associated with resistance to HER2-directed therapy, the study nominates candidate biomarkers that could eventually help clinicians anticipate how a patient’s disease might evolve and which treatments are most likely to help. The authors are clear that these are hypotheses generated from genomic patterns rather than validated clinical tools: further laboratory and clinical studies are needed before they can inform patient care.

The value of shared and integrated genomic data

The study was only possible because of the scale of real-world genomic data now available. Previous research into the genetics of metastatic breast cancer was limited by small sample sizes, a lack of primary-tumor baselines, or sequencing restricted to a handful of known cancer genes. By combining primary tumor data from the International Cancer Genome Consortium with whole-genome sequenced metastatic samples from the Hartwig Medical Database, one of the world’s largest collections of metastatic cancer genomes, the researchers were able to analyze close to 1,300 tumors genome-wide, revealing patterns that smaller or narrower studies could not detect. Hartwig Medical Foundation is proud that its database, built from routine clinical biopsies of patients with advanced cancer across the Netherlands, continues to support independent researchers worldwide in uncovering the biology of cancer spread.

The study, “Breast Cancer Genomic Subtype-Specific Copy Number Alterations in Metastases” by Eason, K. et al., is published in Scientific Reports (2026), DOI: 10.1038/s41598-026-60972-2.

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