Genetic testing takes guess work out of breast cancer treatment

3 minute read

Molecular sequencing pinpoints which triple-negative breast cancer patients need radiation, but it will take time before it’s easily accessible.

US researchers have found a novel way to figure out which triple negative breast cancer patients will respond to immunotherapy alone, and which patients will require further treatment.   

Triple negative breast cancer is more responsive to immunotherapy than other types of breast cancer, but only one in five patients have an objective response to immune checkpoint inhibitors alone. Combining radiotherapy and immunotherapy improves treatment efficacy, but exposes patients to significant toxicity. There is currently no way to tell which patients will benefit from immunotherapy alone and who will require additional treatment. 

But a new clinical trial, published in Cancer Cell, has identified a way to determine which patients will improve with immunotherapy alone and which patients will require radiotherapy or chemotherapy before undergoing surgery.    

“We saw [the] tumours of patients who didn’t respond at all to pre-surgical therapy had no immune cells in them, and [the] tumours of patients who responded right away to immunotherapy were packed with certain types of immune cells,” the study’s senior author, Assistant Professor Simon Knott, said in a statement. 

“But we [also] found another group of patients with tumours that looked quite similar to the tumours of non-responders and didn’t respond to the initial round of immunotherapy. However, they did respond after the combination of immunotherapy and radiotherapy – immune cells invaded the tumours, and the tumours shrank.” 

US researchers biopsied tumours from 34 patients with triple-negative breast cancer at three separate time points: before they began any treatment, after one course of pembrolizumab and after a second course of pembrolizumab combined with radiation therapy. 

Three distinct groups of patients were identified after the biopsy samples underwent single-cell genetic profiling, differing in the types of immune cells within each tumour and the proteins expressed by the cells. 

The first group (non-responders) did not have immune infiltrate before or after therapy and showed minimal therapy-induced immune changes. 

The second group (responders) had increased major histocompatibility complex expression, tertiary lymphoid structures and evidence of anti-tumour immunity prior to immunotherapy. These patients had the strongest T cell response following pembrolizumab treatment.  

The third group (delayed responders) had a similar tumour profile to non-responders at baseline but displayed an immune response characterised by cytotoxic T cells and antigen-presenting myeloid cell interactions after immunotherapy and radiation therapy. 

Dr Nina Stewart, a WA-based radiation oncologist, said that while this approach could have significant impact on breast cancer patients’ lives, it would be some time before there would be changes to clinical practice. 

Dr Stewart said she was interested in seeing whether BRCA1 mutation status could be used as an alternative method for predicting the potential response to treatment, as patients carrying the BRCA1 mutation tend to have immunogenic tumours. 

“We do BRCA1 testing as part of a routine standard of care, and finding a more relevant, readily available surrogate could be an important missing link for translation. It doesn’t have to be perfect to provide much-needed clinical benefit.” 

“Breast radiotherapy is well tolerated, but when you consider the potential treatment and financial toxicity for these patients… any time we can deescalate care would provide a huge impact on a patient’s quality of life. 

“[But] I don’t think this approach would be feasible or possible anywhere but the clinical trial environment at this stage. We’re still going to rely on more rudimentary testing until molecular sequencing or looking at the tumour microenvironment becomes cheaper and more readily available.” 

Cancer Cell 2024, online January 8 

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