PD-L2 Biomarker May Predict Outcomes for Patients with ER-Positive Breast Cancer


The use of PD-L1 to predict outcomes highlights a possible opportunity to better understand which patients with ER-positive breast cancer may benefit from an immune checkpoint inhibitor.

PD-L2, a biomarker seen in breast cancer tumors, was determined a “therapy-relevant” biomarker and may help identifiy patients with estrogen receptor (ER)- positive disease may benefit from treatment with PD-1 inhibitors, according to recent study results.

Dr. Hallgeir Rui, lead author on the study, explained that last year, a new class of drugs, immune checkpoint inhibitors, were approved for triple-negative breast cancer. Patients now have access to PD-1 inhibitors, unless the tumors were ER-positive. So, the purpose of the study was to evaluate whether PD-L2 is a predictor for early recurrence in ER-positive breast cancer.

Results, which were published in the Journal of Clinical Oncology, demonstrated that high PD-L2 expression was associated with a short progression-free survival (time from treatment until disease worsens); 33% of patients fell into this category. This trend remained even after adjustment for different patient characteristics.

“The one thing it could mean is, we now identified the subgroup of patients with estrogen receptor positive breast cancer who could benefit from this type of drug,” said Rui, who is a professor in pathology and vice chair of research at the Medical College of Wisconsin in Milwaukee, in an interview with CURE®. “This would need to be tested in in a clinical trial, but that this is now motivation for clinical trial work.”

Moreover, a sub analysis of patients who were treated with adjuvant chemotherapy (197 patients) also demonstrated the high PD-L2 expression was again associated with shorter progression-free survival.

“(These data are) indicating indirectly … that these patients may benefit from targeted immune checkpoint proteins to break up the functionalities of the PD-L2 protein,” he explained.

This highlights that ER-positive breast cancer may be targeted with this class of drugs, immune checkpoint inhibitors, because this biomarker could predict an outcome.

“Now we have put on the map that estrogen receptor-positive breast cancer maybe targeted by this new class of drugs, and we have a methodology that could identify (that),” he said. “It's not overnight going to change therapy. It's more that we have now a rationale to look among ER-positive breast cancer to find potential responding tumors, those patients could benefit from the drug if a follow up clinical trial can show evidence for this. So again, it's a step towards … certainly potentially, and possibly likely identifying a new group of breast cancer patients who could benefit from this type of drugs.”

Understanding a biomarker, such as PD-L2, is important because it can tell researchers how a patient may react to a treatment. Rui explained that immune checkpoint inhibitors are potent drugs and can cause side effects, so they do not want to give it to someone who might not have a good outcome.

“Progress is continuing to be the made in understanding how the immune system may be exploited to improve breast cancer therapy in general, and specifically for patients with estrogen receptor positive breast cancer,” he said. “I think that's a key message that this is a step towards continued improved understanding so we can apply these potent drugs to the right patients.”

However, there is no established test for PD-L2 in the clinic currently. So, it is important that patients advocate for themselves and request that type of test, Rui noted.

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