Multigene RNA signature enhances treatment strategies for triple negative breast cancer

BMJ GroupOct 23 2024

Using a gene signature technique to tailor chemotherapy for patients with early triple negative breast cancer shows promise as a way to improve disease-free survival, finds a clinical trial published by The BMJ today.

Triple negative breast cancer is an aggressive type of breast cancer that carries a higher risk of recurrence and death after standard treatment. As such, there is an urgent need for more effective chemotherapy strategies.

Multigene signatures are tests that analyse genes in a tumour sample to predict how well a patient will respond to chemotherapy and the risk of their cancer returning to help guide treatment decisions, but validated signatures for triple negative breast cancer are scarce.

So researchers in China set out to test the feasibility of using a multigene RNA signature to tailor chemotherapy for patients with operable triple negative breast cancer.

The trial enrolled 504 female patients aged 18-70 years at seven cancer centres in China who had undergone surgery for early stage triple-negative breast cancer between January 2016 and July 2023.

Patients classified by the signature as being at high risk were randomised to receive intensive chemotherapy or standard chemotherapy. Patients at low risk also received standard chemotherapy.

After an average follow-up period of 45 months, three year disease-free survival was significantly better among participants at high risk who received the more intensive treatment than in those receiving standard care (91% v 81%). However, the result for the three year overall survival rate was less certain (98% v 91%).

Patients classified as being at low risk had significantly higher rates of disease-free survival, recurrence-free survival, and overall survival than patients at high risk receiving the same standard chemotherapy. 

As expected, intensive chemotherapy carried a higher risk of serious adverse events, but there were no treatment related deaths.

The researchers acknowledge several limitations, such as the open-label design (where both health providers and patients are aware of the treatment being given), and note that the findings may not apply to other populations.

However, they say this trial "marks a pivotal advance, showing for the first time the feasibility of using multigene signatures to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer."

"In addition, this study provides independent external validation of the prognostic value of the integrated signature in a uniformly treated population," they conclude.

How can this risk score be used to improve practice, ask Australian researchers in a linked editorial?

"A validated predictive test could enhance treatment decisions for many patients, perhaps to guide selection of neoadjuvant chemotherapies such as anthracyclines and platinum agents alongside novel treatments," they explain. 

"Hopefully this score, and others, will contribute to a future in which treatment is more personalised, more targeted, and less reliant on conventional cytotoxic chemotherapy for people with this difficult subtype of breast cancer," they conclude.