New test predicts ER+/HER2+ breast cancer relapse in 2 weeks
Changes in the intrinsic subtype of an ER+/HER2+ tumor after 2 weeks of hormone therapy can tell us the optimal treatment strategy going forward by predicting the risk of relapse.
Scientists from The Institute of Cancer Research (London, UK) have identified a quick and simple test that can assess the risk of cancer returning in ER+/HER2+ breast cancer patients. This test involves analyzing tumor subtype changes after a brief course of hormone therapy.
The current standard of care for ER+/HER2+ breast cancer patients involves five years of aromatase inhibitor (AI) therapy, but these tumors are highly heterogenous and responses to these hormone treatments can vary. With 200,000 new cases of ER+/HER2+ breast cancer each year, improving our understanding of how the tumors respond to peri-operative AI (POAI) treatment is essential.
The Phase III POETIC trial assessed whether POAI improved outcomes in ER+ breast cancer, and while it didn’t demonstrate clear benefits for all patients, this new research has shown that the effect of the treatment on the tumors’ intrinsic subtype can inform on the optimal post-surgery treatment strategy for each patient.
The researchers analyzed 213 tumors taken from patients who had undergone 2 weeks of hormone treatment with AIs prior to surgery as part of the Phase III POETIC trial. Results showed that some of these tumors had changed subtype during this treatment, which can provide valuable information on the risk relapse in each patient. While treatment of ER+/HER2+ breast cancer presents many challenges, the development of this prognostic test offers an opportunity to tailor treatment strategies for each patient.
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The research looked at two subtypes of ER+/HER2+ tumors defined by their distinctive molecular and genetic features, called Luminal A and Luminal B, with the latter being associated with a higher risk of relapse. They found that 2 weeks of the hormone therapy altered the characteristics of some tumors, causing their subtype to change. The lowest chance of relapse was seen in the 19% of tumors that remained as Luminal A throughout the treatment, and these patients could therefore remain on the standard of care hormone treatment. 28% of the 213 tumors changed from Luminal B to Luminal A, indicating a positive response to the POAI treatment the patients could also continue with the hormone treatment. However, tumors that did not shift from Luminal B demonstrated a 1.5x higher chance of subsequent relapse than those that moved to Luminal A, meaning these patients would require more intensive treatment to prevent relapse, such as the use of CDK4/6 inhibitors.
The findings of this study show that the outcomes of having 2 weeks of hormone therapy before surgery can be used to guide clinical decision making. By testing for changes in the tumor’s subtype both before and after POAI, clinicians can develop personalized treatment plans for each patient, as opposed to proceeding with a plan based off just the initial subtype. This can help prevent unnecessarily intensive treatments being used on patients who have a low risk of relapse, preventing unnecessary side effects, while allowing patients with aggressive tumors to be offered more effective, intensive treatments.
“Ultimately, our findings move us closer to more precise, patient-centred care for this over-looked breast cancer subtype.” stated the senior author of the paper, Maggie Cheang (Institute of Cancer Research, London, UK)