Risk-based decision-making in the treatment of HER2-positive early breast cancer: Recommendations based on the current state of knowledge

Christian Jackisch, Patricia Cortazar, Charles E. Geyer, Luca Gianni, Joseph Gligorov, Zuzana Machackova, Edith A. Perez, Andreas Schneeweiss, Sara M. Tolaney, Michael Untch, Andrew Wardley, Martine Piccart

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Treatment of HER2-positive early breast cancer (EBC) continues to evolve with neoadjuvant (pre-operative) and adjuvant (post-operative) HER2-targeted therapies as standard of care. There are two important decision points. The first involves deciding between neoadjuvant therapy or proceeding directly to surgery. Neoadjuvant chemotherapy (NACT) plus pertuzumab–trastuzumab is appropriate for patients with high-risk HER2-positive EBC (tumour diameter ≥2 cm, and/or node-positive disease). Patients with node-negative disease and tumour diameter <2 cm are candidates for upfront surgery followed by paclitaxel for 12 weeks plus 18 cycles of trastuzumab, with the option to add pertuzumab (if pN+). The second decision point involves the pathohistological result at surgery after neoadjuvant therapy. Total pathological complete response (tpCR: ypT0/is, ypN0) is associated with improved survival endpoints. Patients with tumours ≥2 cm and/or node-positive disease at diagnosis who have a tpCR after dual blockade should continue pertuzumab–trastuzumab in the adjuvant setting to complete 1 year (18 cycles) of treatment. For patients with invasive residual disease, 14 cycles of post-neoadjuvant trastuzumab emtansine (T-DM1) therapy significantly increases invasive-DFS compared with trastuzumab. Extended adjuvant therapy with neratinib is an option in selected patients (HER2-positive and oestrogen receptor [ER]-positive) who have completed adjuvant trastuzumab-based therapy. Less aggressive chemotherapy regimens are recommended in populations with a lower risk of recurrence (patients with small tumours without axillary involvement; patients unlikely to tolerate anthracycline-taxane or taxane-carboplatin regimens). Ultimately, treatment recommendations should be consistent with local and international guidelines. Further studies will guide optimisation of treatment for patients with HER2-positive EBC according to the risk of disease recurrence.

Original languageEnglish (US)
Article number102229
JournalCancer Treatment Reviews
Volume99
DOIs
StatePublished - Sep 2021

Keywords

  • HER2-postive early breast cancer
  • Neoadjuvant therapy
  • Neratinib
  • Pertuzumab
  • T-DM1
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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