Using the HER2/CEP17 FISH Ratio to Predict Pathologic Complete Response Following Neoadjuvant Anti-HER2 Doublet Therapy in HER2+ Breast Cancer

Oncologist. 2023 Feb 8;28(2):123-130. doi: 10.1093/oncolo/oyac247.


Background: Clinical trials of HER2-directed therapy that omit neoadjuvant conventional chemotherapy for HER+ breast cancer demonstrate that a subset of patients still obtains a pCR. Identifying tumor characteristics which predict pCR may help select patients for de-escalated neoadjuvant dual HER2-targeted treatment without chemotherapy. This is the first study evaluating the HER2/CEP17 ratio by FISH as a biomarker to predict pCR among patients who received neoadjuvant anti-HER2 regimens without chemotherapy.

Patients and methods: Data from patients with locally advanced HER2+ breast cancer who received neoadjuvant dual HER2-targeted therapy without conventional chemotherapy from a single center was retrospectively reviewed. All patients were enrolled in one of 3 clinical trials evaluating chemotherapy de-escalation. Logistic regression modeling assessed for a relationship between the HER2/CEP17 FISH ratio obtained from baseline tissue biopsy and pCR based on pathology at the time of definitive breast surgery following neoadjuvant treatment.

Results: Following neoadjuvant treatment with dual HER2-targeted therapies in 56 patients, the probability of pCR was 73% among patients with a HER2 ratio of 13.1 compared to a probability of 38% among patients with HER2 ratio of 5.5 (OR 4.14, 95% CI 1.44-11.89; P = .012). This positive association persisted after controlling for different treatment regimens administered (OR 2.87, 95% CI 0.9-9.18, P = .020).

Conclusions: These data found a positive association between the HER2/CEP17 FISH ratio and pCR following neoadjuvant dual HER2-targeted therapy without chemotherapy. Larger prospective studies are needed to validate the HER2 ratio as a biomarker to select patients for neoadjuvant dual anti-HER2 therapy without chemotherapy.

Keywords: HER2/CEP17 FISH ratio; HER2; breast cancer; pathologic complete response; pertuzumab; trastuzumab.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Neoadjuvant Therapy* / adverse effects
  • Receptor, ErbB-2 / therapeutic use
  • Retrospective Studies
  • Trastuzumab / therapeutic use


  • Receptor, ErbB-2
  • Trastuzumab
  • DNA-Binding Proteins