According to the World Health Organization (WHO), nearly 2.3 million women worldwide were diagnosed with breast cancer in 2022, making it the most common cancer among women globally. While treatments such as surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapies are widely used, not every treatment proves equally effective for every patient. Success often depends on tumour type, disease stage, and the patient’s overall health, making it challenging for clinicians to predict treatment outcomes in advance.
A recent study published in Clinical Cancer Research has highlighted a promising new tool: a form of “liquid biopsy” capable of predicting, in advance, how well patients with advanced breast cancer might respond to targeted therapies.
Detecting Circulating Tumour DNA
The research, conducted under the ‘PlasmaMATCH’ trial, analysed blood samples from 176 patients with advanced breast cancer. Scientists focused on detecting circulating tumour DNA (ctDNA), tiny fragments of DNA released from cancer cells into the bloodstream.
Participants were divided into two groups based on cancer subtype and genetic mutations:
| Group | Number of Patients | Characteristics |
|---|---|---|
| Group 1 | 82 | Patients with genetic alterations in ESR1, HER2, AKT1, AKT, or PTEN |
| Group 2 | 94 | Triple-negative breast cancer patients with no identifiable genetic alterations |
ctDNA levels were measured before treatment and four weeks into therapy.
ctDNA as a Biomarker for Treatment Response
In Group 1, patients whose ctDNA was undetectable four weeks into treatment had significantly better outcomes. Their progression-free survival (PFS) averaged 10.6 months, compared to just 3.5 months for those with detectable ctDNA. Among those with low ctDNA levels, 46.2% showed a positive response to therapy, versus only 7.9% in the high ctDNA subgroup.
Group 2 showed similar trends. Patients with low ctDNA at baseline experienced an average PFS of 10.2 months, while those with high ctDNA had a PFS of 4.4 months. Treatment response rates were 40% for the low ctDNA group, compared to 9.7% for the high ctDNA group. Notably, patients with undetectable ctDNA experienced disease control for nearly 12 months, with 85.7% responding positively, whereas those with detectable ctDNA averaged 4.3 months PFS and an 11.4% response rate.
Dr Isalt Brown, Clinical Research Fellow at the Institute of Cancer Research, London, explained, “By analysing ctDNA before and after initial therapy, we can identify which patients are likely to respond to treatment, offering a personalised approach to care.”
Hope for Metastatic Breast Cancer Patients
Dr Richard Reitherman, Medical Director of Breast Imaging at MemorialCare Breast Center in California, emphasised that the trial involved patients with metastatic breast cancer, where tumours had spread beyond the breast and lymph nodes to organs such as bones, liver, or lungs. “Detecting and treating cancer at this stage is extremely challenging,” he noted. “Monitoring ctDNA offers a method to predict treatment efficacy before changes are visible via imaging.”
Dr Richard Zelkowitz, Medical Director of Breast Oncology at Hartford Healthcare Cancer Institute, described the findings as “a potential game-changer.” He added, “Tracking circulating DNA allows clinicians to adjust treatment rapidly, ensuring patients receive the most effective therapy. This personalised approach could markedly improve outcomes and quality of life.”
Liquid biopsies for ctDNA may revolutionise the management of advanced breast cancer, offering timely predictions of treatment success and providing new hope for patients facing metastatic disease.