Anti-HER2 therapy response assessment for guiding treatment (de-)escalation in early HER2-positive breast cancer using a novel deep learning radiomics model

ObjectivesAnti-HER2 targeted therapy significantly reduces risk of relapse in HER2+breast cancer. New measures are needed for a precise risk stratification to guide (de-)escalation of anti-HER2 strategy.MethodsA total of 726 HER2+cases who received no/single/dual anti-HER2 targeted therapies were split into three respective cohorts. A deep learning model (DeepTEPP) based on preoperative breast magnetic resonance (MR) was developed. Patients were scored and categorized into low-, moderate-, and high-risk groups. Recurrence-free survival (RFS) was compared in patients with different risk groups according to the anti-HER2 treatment they received, to validate the value of DeepTEPP in predicting treatment efficacy and guiding anti-HER2 strategy.ResultsDeepTEPP was capable of risk stratification and guiding anti-HER2 treatment strategy: DeepTEPP-Low patients (60.5%) did not derive significant RFS benefit from trastuzumab (p=0.144), proposing an anti-HER2 de-escalation. DeepTEPP-Moderate patients (19.8%) significantly benefited from trastuzumab (p=0.048), but did not obtain additional improvements from pertuzumab (p=0.125). DeepTEPP-High patients (19.7%) significantly benefited from dual HER2 blockade (p=0.045), suggesting an anti-HER2 escalation.ConclusionsDeepTEPP represents a pioneering MR-based deep learning model that enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thereby providing valuable guidance for anti-HER2 (de-)escalation strategies. DeepTEPP provides an important reference for choosing the appropriate individualized treatment in HER2+breast cancer patients, warranting prospective validation.Clinical relevance statementWe built an MR-based deep learning model DeepTEPP, which enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thus guiding anti-HER2 (de-)escalation strategies in early HER2-positive breast cancer patients.Key Points center dot DeepTEPP is able to predict anti-HER2 effectiveness and to guide treatment (de-)escalation.center dot DeepTEPP demonstrated an impressive prognostic efficacy for recurrence-free survival and overall survival.center dot To our knowledge, this is one of the very few, also the largest study to test the efficacy of a deep learning model extracted from breast MR images on HER2-positive breast cancer survival and anti-HER2 therapy effectiveness prediction.