HER2+Breast Cancer Escalation and De-Escalation Trial Design: Potential Role of Intrinsic Subtyping

Simple Summary Classical clinical research has been developed according to immunohistochemical breast cancer subtypes, instead of designing trials specifically for each molecular subtype. Efforts in de-escalating treatment should focus on identifying a subgroup of HER2 oncogene addicted tumours that are especially sensitive to anti-HER2 therapies and, thus, spare unnecessary treatments. A prognostic assay that integrates molecular tumour features with clinical and pathologic variables and accurately defines a group of HER2 addicted tumours remains the best candidate among these strategies. Long-term outcomes in breast cancer patients differ based on the molecular subtype, with HER2-E being the most aggressive one. Advances in clinical practice have dramatically shifted HER2+ breast cancer prognosis. Risk adapted strategies to individualize therapies are necessary. De-escalation approaches have been encouraged based on the risks of clinical-pathological factors. Molecular gene subtyping could further accurately define HER2 addicted tumours that are sensitive to anti-HER2 therapies, thus sparing unnecessary treatments. The transition from immunochemistry to molecular profiling in HER2+ breast cancer is discussed.