Whole genome sequencing (WGS) could transform breast cancer diagnosis and treatment by enabling truly personalized care, according to new research from the University of Cambridge. The study, published in The Lancet Oncology, shows that analyzing the complete genetic makeup of patients and their tumors can identify treatment targets, predict disease progression, and match patients to clinical trials faster and more accurately.
Breast cancer remains the most common cancer worldwide, affecting 2.3 million women each year. Despite major progress, treatment selection still largely relies on general tumor characteristics rather than individual genetic profiles. Whole genome sequencing offers a more detailed approach, mapping every DNA change that drives tumor growth or influences treatment response.
Rich source of information
Professor Serena Nik-Zainal, from Cambridge’s Department of Genomic Medicine, explains: “Whole genome sequencing provides an incredibly rich source of information that can guide treatment, but its full potential has yet to be realized, especially for common cancers like breast cancer.”
Her team analyzed genomic data from 2,500 breast cancer patients through England’s 100,000 Genomes Project, linking DNA patterns with treatment outcomes over five years. The results revealed that 27% of breast cancers contained genetic features that could immediately guide therapy or clinical trial selection, equivalent to more than 15,000 women annually in the UK. These included DNA repair defects, drug-targetable mutations, and genetic markers of resistance to hormone therapy.
An additional 15% of cases had genetic signatures that could inform future drug development and research. The retrospective analysus study was published in The Lancet Oncology
Prognosis and treatment intensity
Beyond treatment targeting, WGS also revealed key insights into prognosis. In the most common breast cancer subtype (ER+HER2−), specific DNA alterations, such as large-scale structural changes or mutations in the TP53 gene, were found to predict poorer outcomes more accurately than traditional clinical measures like tumor grade or patient age.
The researchers developed a clinical framework to help oncologists determine which patients might benefit from more intensive therapies and which could safely receive less aggressive treatment. This could potentially optimize care for around 7,500 women annually with early-stage or low-grade tumors.
Innovation through data-driven trials
According to Professor Nik-Zainal, these findings highlight how WGS can redefine clinical trial recruitment. Instead of testing for one or two known mutations, researchers could use full genomic profiles to connect patients to multiple trials simultaneously, dramatically speeding up access to promising new therapies.
“The UK is uniquely positioned to lead this transformation,” she said. “With the NHS Genomic Medicine Service, we now have the infrastructure to deliver whole genome sequencing at scale, turning population-level data into personalized care that saves lives.”
This research underscores a pivotal shift toward genomic-driven oncology, where every breast cancer patient’s treatment could one day be guided by the unique genetic signature of their disease.
