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. ABSTRACT: 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.