Evaluation of [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT for Predicting Pathological Complete Response After Neoadjuvant Chemotherapy in HER2 Positive Early Breast Cancer

Evaluation of [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT for Predicting Pathological Complete Response After Neoadjuvant Chemotherapy in HER2 Positive Early Breast Cancer (GATHER): a Study Protocol for a Monocentric, Prospective, Interventional, Phase 2, Imaging Biomarker Trial.

The GATHER trial aim to evaluate the diagnostic performance of [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT in predicting pCR following neoadjuvant chemotherapy. This study is part of the development of new functional, non-invasive approaches with the aim of offering personalized therapeutic approaches.

In early-stage HER2-positive breast cancer, neoadjuvant chemotherapy is frequently required, and pathological complete response (pCR) correlates with excellent prognosis. However, no non-invasive imaging method reliably predicts pCR, making surgery mandatory despite its aesthetic, functional, and psychological burden. Recently, new functional imaging tracers targeting the HER2 protein have been developed. Among these, [68Ga]Ga-NOTA-anti-HER2-sdAb is of particular interest due to its molecular characteristic; it has demonstrated favorable safety profile and ability to identify HER2+ cells in vivo. This trial evaluates its ability to predict pCR, with the prospect of paving the way for future therapeutic de escalation and surgical sparing.

Inclusion Criteria:

• Female aged 18 years or older
• Histologically proven HER2-positive early breast cancer, defined as IHC 3+ or IHC 2+ with ISH amplification
• Indication for neoadjuvant chemotherapy combined with anti-HER2 targeted therapy followed by surgery, as determined by a multidisciplinary tumor board
• ECOG performance status of 0 or 1
• Affiliated to or beneficiary of a social protection scheme
• Written informed consent signed prior to any study-specific procedure

Exclusion Criteria:

• Pregnant or breastfeeding women

  • Patient not treated with curative intent
  • History of ipsilateral breast cancer treated by surgery and/or radiotherapy
  • Lobular histology
  • Known contraindication or hypersensitivity to [68Ga]Ga-NOTA-anti-HER2-sdAb or any of its radiopharmaceutical excipients
  • Known contraindication or hypersensitivity to [18F]F-FDG or any of its radiopharmaceutical excipients
  • Concurrent enrollment in another clinical trial evaluating radiopharmaceuticals
  • Patient under guardianship, curatorship, or judicial protection
  • Patient deprived of liberty
  • Inability to understand the study or comply with trial constraints due to linguistic, psychological, or geographical barriers