Early-stage HER2+ Breast Cancer

Early-stage HER2+ Breast Cancer: overview

This algorithm covers early-stage HER2-positive breast cancer and branches first on tumor size and nodal status, then on response to neoadjuvant therapy.

For tumors under 2 cm that are node negative, the chart begins with surgery. Patients with pT1 pN0 disease receive weekly paclitaxel plus trastuzumab for 12 weeks (Tolaney, NEJM 2015), then complete 1 year of trastuzumab. If surgery shows pT2 or pN1 or greater disease, adjuvant chemotherapy plus trastuzumab with or without pertuzumab is given, supported by APHINITY. For tumors 2 cm or larger or node-positive disease, neoadjuvant chemotherapy plus trastuzumab and pertuzumab is used (NeoSphere, APHINITY), followed by surgery. Patients with a pathologic complete response complete 1 year of trastuzumab with or without pertuzumab. Patients with residual disease switch to T-DM1 for 14 cycles to complete 1 year, based on KATHERINE, which halved the relative risk of recurrence or death. Extended neratinib for 1 year may be considered afterward, particularly in HR-positive, node-positive disease (ExteNET).

Step by step

• Tumor under 2 cm and node negative: surgery first.
• pT1 pN0 at surgery: weekly paclitaxel plus trastuzumab for 12 weeks, then complete 1 year of trastuzumab (Tolaney, NEJM 2015).
• pT2 or pN1 or greater at surgery: adjuvant chemotherapy plus trastuzumab with or without pertuzumab (APHINITY).
• Tumor 2 cm or larger or node positive: neoadjuvant chemotherapy plus trastuzumab and pertuzumab (NeoSphere, APHINITY), then surgery.
• Pathologic complete response: complete 1 year of trastuzumab with or without pertuzumab (APHINITY).
• Residual disease: T-DM1 for 14 cycles to complete 1 year (KATHERINE).
• After either path, consider neratinib for 1 year in HR-positive, node-positive disease (ExteNET).

Trials behind this algorithm

• APHINITY Piccart M et al, JCO, 2021; PMID: 33539215
• NeoSphere Gianni L et al, Lancet Oncol, 2012; PMID: 22153890
• ExteNET Martin M et al, Lancet Oncol, 2017; PMID: 29146401
• KATHERINE von Minckwitz G et al, NEJM, 2019; PMID: 30516102

Background reading: Breast Cancer (Part 2): DCIS, Early-Stage and Metastatic Treatment board review notes.