Advances in Whole Genome Sequencing Enhance Breast Cancer Treatment and Clinical Trial Matching

Recent research from the University of Cambridge highlights the growing potential of whole genome sequencing (WGS) to revolutionize breast cancer care. The study, published in The Lancet Oncology, demonstrates that applying WGS to breast cancer patients can uncover unique genetic features that inform personalized treatments and facilitate matching patients with suitable clinical trials.

In 2022, approximately 2.3 million women globally were diagnosed with breast cancer, with around 670,000 fatalities. Despite medical advances, accurately tailoring treatments to individual genetic profiles remains challenging. WGS involves analyzing the complete DNA of both the tumor and the patient, revealing genetic mutations and vulnerabilities that drive cancer progression. This information can identify potential treatment targets, resistance mechanisms to current therapies like hormone therapy, and specific mutational signatures.

Though the cost of sequencing has significantly decreased—recently announced at around US $100 per genome—its routine use within the UK's NHS is limited, currently available only for some adult, pediatric, and metastatic cancers via the NHS Genomic Medicine Service. Professor Serena Nik-Zainal from the University of Cambridge emphasizes that while WGS has great promise, its full potential is hampered by a lack of extensive clinical studies and the overwhelming richness of genetic data.

The researchers analyzed data from nearly 2,500 women within England’s National Genomic Research Library, part of the 100,000 Genomes Project, linked to clinical and mortality records over five years. They identified genetic features in about 27% of breast cancer cases that could immediately guide treatment decisions—using existing drugs or directing patients toward ongoing clinical trials. Notably, defects in DNA repair mechanisms such as homologous recombination deficiency (HRD) were present in 12% of cases, alongside other mutations indicating drug resistance and therapeutic vulnerabilities.

Furthermore, an additional 15% of cases displayed genetic features valuable for future research, such as alternative DNA repair pathway issues. Genetic markers also provided more accurate prognosis insights—particularly in ER+HER2- breast cancer, the most common subtype—where DNA structural changes, mutational signatures, and TP53 mutations correlated with higher mortality risk. These findings could help stratify patients for more or less aggressive treatments, potentially improving survival outcomes.

Prof. Nik-Zainal notes that the UK's leadership in population-level genomic sequencing offers a remarkable opportunity to integrate WGS into routine breast cancer management. The implementation could significantly enhance patient-specific care and accelerate the recruitment process in clinical trials by allowing comprehensive genetic profiles rather than single mutation testing.

The study underscores the transformative impact of WGS not only on personalized medicine but also on trial design, where broader genetic data could streamline participant recruitment and enhance the development of novel therapies. As Prof. Nik-Zainal explains, utilizing entire genetic readouts increases the scope of trials and expediates the delivery of effective treatments to patients who need them most.

Source: [https://medicalxpress.com/news/2025-10-genome-sequencing-breast-cancer-patients.html]