The advent of HER2-targeted therapies has led to an important shift in the management of HER2-positive early breast cancer. However, initial treatment approaches apply uniform treatment regimens to all patients, with significant treatment-related and financial toxicities for both the patient and the health care system. Recent data demonstrates that for many patients, the chemotherapy backbone, duration and nature (mono- versus dual-targeted therapy) of the HER2 blockade can be better targeted to an individual patient’s risk of recurrence. We will provide a review of current data supporting risk tailored therapy in early stage HER2-positive breast cancer along with key completed and ongoing Canadian and international risk tailored trials. Neoadjuvant systemic therapy should now be considered for patients with clinical stage 2 disease, with greater use of non-anthracycline based chemotherapy regimens. Patients with residual disease following neoadjuvant therapy should be considered for escalated treatment with adjuvant T-DM1. Patients with stage I disease can often be managed with upfront surgery and evidence-based de-escalated adjuvant chemotherapy regimens. The modest benefit of 12- versus 6 months of adjuvant HER2 therapy and/or dual adjuvant HER2 therapy should be carefully weighed against the toxicities. All patients with HER2-positive breast cancer should be enrolled in ongoing risk tailored treatment trials whenever possible. Increasing data supports risk tailored therapy in early stage HER2-positive breast cancer in place of the routine application of aggressive and toxic systemic therapy regimens to all patients. While much progress has been made towards treatment de-escalation in appropriate patients, more is needed, as we highlight in this review. Indeed, Canadian-led clinical trials are helping to lead these efforts.
This is an open access article distributed under the Creative Commons Attribution License
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.