The Lancet Oncology reports that offering entire DNA analysis to women with breast cancer can uncover distinctive genomic clues, aiding immediate care decisions and guiding entry into clinical studies, researchers at the University of Cambridge explain.
In 2022, 2.3 million women worldwide received a breast cancer diagnosis and 670,000 died from it. Despite advances, clinicians still struggle to pinpoint the optimal therapy for each individual and to foresee which cases will behave more aggressively.
Whole‑genome sequencing compares the DNA of a patient and their tumour to identify mutations that drive the disease. The information reveals why a tumour started, which pathways are active, and can flag weaknesses that drugs might exploit or resistance that could arise.
While costs are falling—Ultima Genomics has claimed a $100 price for a human genome—the technique is not yet routine across the United Kingdom’s National Health Service (NHS). Through the NHS Genomic Medicine Service, it is currently reserved for select adult cancers, rare cancers, pediatric cancers, and certain metastatic disease.
Professor Serena Nik‑Zainal of Cambridge’s Department of Genomic Medicine and Early Cancer Institute says, “Whole‑genome sequencing is becoming feasible for cancer care, yet it remains under‑used, especially for common cancers.”
She added, “Part of the issue is the lack of clinical evidence supporting its use, but another factor is simply the sheer volume of data it generates, which can be intimidating to interpret.”
To tackle these barriers, Nik‑Zainal’s team analysed data from nearly 2,500 women across England stored in the National Genomic Research Library, a world‑leading repository managed by Genomics England. The cohort, recruited through the 100,000 Genomes Project, was linked to medical and mortality records, enabling five‑year outcome tracking.
The investigators searched for mutations that cause or influence breast cancer, with a focus on defects in DNA‑repair pathways.
They discovered that about 27% of cancers exhibited genomic features that could inform a personalised strategy promptly—either through existing medications or by enrolling patients in ongoing or planned trials. In the UK, this represents more than 15,000 women annually.
Identified markers included homology‑directed repair deficiency (HRD) in roughly 12% of cases; unique drug‑targetable mutations; evidence of hormone‑therapy resistance; and mutational fingerprints that expose therapeutic vulnerabilities.
Another 15% of tumours displayed characteristics useful for future research, such as alternate DNA‑repair defects, equating to over 8,300 women a year.
The study also shed light on prognosis. For the most prevalent subtype, estrogen‑receptor positive, HER2‑negative breast cancer (≈70% of diagnoses), specific genetic signatures predicted aggressive behaviour more accurately than conventional factors like age, stage, or tumour grade. Notable predictors were extensive structural DNA rearrangements, APOBEC‑related mutational patterns, and TP53 mutations.
Using these insights, the team devised a decision framework to help clinicians determine which patients would benefit from intensified treatment and which could safely receive less intensive regimens. The model suggested that around 7,500 women each year with low‑grade tumours might still merit stronger therapy.
Professor Nik‑Zainal highlighted that the UK’s NHS is a global leader in applying whole‑genome sequencing through the Genomic Medicine Service. “Now that we have population‑level evidence of its impact, we can meaningfully improve thousands of patients’ care each year, tailoring treatment more precisely,” she said.
Beyond individual care, comprehensive genome data can revolutionise how patients are selected for and managed in clinical trials, accelerating the arrival of new treatments.
She added, “At present we screen for only a handful of mutations and invite patients into trials that target those changes. With full genomic profiles, we’re no longer limited to single‑target studies; we can open up recruitment to multiple trials simultaneously, making the process faster and ensuring patients receive the right therapy sooner.”