Loss of HER2-positivity following neoadjuvant targeted therapy for breast cancer is not associated with inferior oncologic outcomes

J Surg Oncol. 2021 Dec;124(8):1224-1234. doi: 10.1002/jso.26646. Epub 2021 Aug 20.

Abstract

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are treated with trastuzumab-based neoadjuvant therapy (NAT); some patients with residual disease post-NAT show loss of HER2 amplification and has been inconsistently associated with oncologic outcomes.

Methods: We queried our multi-institutional cancer registry for women with HER2-positive breast cancer undergoing NAT from 2011 to 2018. Clinicopathologic, treatment-related, and outcomes data were collected. Kaplan-Meier and Cox proportional hazards analysis were used to evaluate oncologic outcomes.

Results: A total of 348 patients were identified; 166 (48%) had a pathologic complete response. Of the 182 patients with residual disease, 87 (48%) were HER2-positive, 34 (19%) were HER2-negative, and 61 (33%) were HER2-unknown, with a median follow-up of 44 months. There were no factors associated with HER2 loss apart from age. On Kaplan-Meier analysis, estimated 5-year recurrence-free survival (RFS) and overall survival (OS) for patients with HER2-positive residual disease was 81% and 92%, respectively, and 74% (log rank p = 0.75) and 81% (p = 0.35) in patients with HER2-negative residual disease.

Conclusion: The loss of HER2-positivity following NAT is not associated with worse 5-year RFS or OS. We do not recommend retesting HER2 status following NAT for the purpose of clinical management; these patients should complete targeted adjuvant therapy.

Keywords: HER2; breast cancer; neoadjuvant therapy; trastuzumab.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / mortality*
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2