Trastuzumab significantly improves outcomes in early HER2-positive breast cancer, irrespectively of any prognostic or predictive factors. Unfortunately, about a quarter of patients receiving neoadjuvant trastuzumab experience disease recurrence, revealing the unquestionable need for further improvement of treatment outcomes.

Adding HER2 blockade to adjuvant trastuzumab with pertuzumab and neratinib improves invasive disease-free survival (IDFS), particularly for those at highest risk of recurrence. A shift toward a neoadjuvant strategy for patients with a higher risk of recurrence could result in further treatment optimization. For patients without a pathological complete response (pCR) after the neoadjuvant part of the therapy, a switch to adjuvant trastuzumab emtansine significantly improves IDFS and distant recurrence-free survival and shows a trend towards improved overall survival (OS). On the other hand, for low-risk patients, chemotherapy deescalation should be strongly considered with the use of trastuzumab monotherapy as an anti-HER2 backbone.

Neoadjuvant therapy should be offered for a significant proportion of HER2-positive early breast cancer patients with a higher risk of recurrence. Postneoadjuvant treatment should be tailored according to the initial stage of disease and the response to neoadjuvant treatment.