A new study has shed light on the genetic messages encoded by genes within ‘triple negative’ breast cancers (TNBC), and shows they could predict response to chemotherapy.
The study, by researchers at The Institute of Cancer Research, London, shows that certain characteristics within patients’ primary tumours can predict how they will respond to different treatments after their tumours have spread around the body.
For example, women whose primary tumours have a higher presence of immune cell genes, and genes linked to their activity, are more likely to respond to docetaxel than carboplatin.
Additionally, patients whose cancer has spread but who have not yet received chemotherapy, and whose primary tumours have markers of faults in genes linked to DNA repair pathways, tend to respond better to carboplatin.
“Our findings paint a complex picture – with many, dynamic factors driving how tumours respond to treatment.”
The findings suggest it might be possible to predict who will benefit from carboplatin and docetaxel using a range of different biomarkers and suggest further investigation of these biomarkers in clinical trials is warranted.
The presence of these biomarkers could be used to accelerate the development of more personalised treatments for triple negative breast cancers.
Triple negative cancers are not driven by any of the three molecules that can be blocked by targeted hormone receptor drugs – the HER2 protein and two hormone receptors for oestrogen and progesterone – and so current treatment options are limited.
Cancers evolve between therapy and recurrence
The researchers also explored whether immune signatures were conserved between primary tumour samples and secondary tumour samples taken after the cancer had become metastatic.
Although immune features remained relatively stable, RNA-based features related to DNA damage repair pathways changed significantly.
The authors therefore recommend against doctors routinely using biopsies taken from primary tumour samples to carry out gene-expression (RNA)-based biomarker tests for guiding the treatment for secondary cancers.
They suggest it would be better to use biopsies taken from secondary tumours as the cancers can evolve between first diagnosis and recurrence after initial therapy.
Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robins Research Centre at the ICR, said: “Our analysis takes a deep dive into tumour biology and how different tumour characteristics can predict which treatment patients’ tumours will respond to. Our findings paint a complex picture – with many, dynamic factors driving how tumours respond to treatment. I hope this work will contribute to a future where patients with triple negative breast cancer have more effective and personalised treatment options which extend their lives.”
Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World