Efficacy Study of Herceptin to Treat HER2-negative CTC Breast Cancer (TREAT-CTC)

Inclusion Criteria:

• Female gender
• WHO performance status 0-1

• Non-metastatic and non-relapsed operable primary invasive HER2 negative adeno-carcinoma of the breast that is adequately excised and all of the following:

  • histological grade > 1 at the time of surgery (all patients) and primary tumor size > 1 cm
  • the patient should have completed either
  • adjuvant chemotherapy for node-positive disease (pN ≥1, macrometastasis only) or
  • neoadjuvant chemotherapy. In this case, no pathological complete response (defined as any residual invasive disease in breast or lymph nodes) after neoadjuvant chemotherapy is required.
• Availability of peripheral blood draw for CTC blood test
• Tumor block or unstained slides of primary tumor must be available prior to randomization for centralized HER2 testing
• Prior chemotherapy with doxorubicin restricted to a total dose of 360 mg/m2 or with epirubicin restricted to a total dose of 720 mg/m2 is allowed.
• Adjuvant hormonal therapy or adjuvant radiotherapy (if applicable) is allowed upon physician's choice
• The interval between definitive surgery (neoadjuvant group) or end of adjuvant chemotherapy (adjuvant group) and registration must be at least 3 weeks but no more than 12 weeks.

Exclusion Criteria:

• No further adjuvant chemotherapy treatment planned.
• No prior use of anti-HER2 therapy for any reason or other prior use of biological agent or immunotherapy for BC
• No prior and/or concomitant use of bisphosphonate therapy for any reason is allowed.
• No prior mediastinal irradiation except internal mammary node irradiation for the present BC
• No history of prior (ipsilateral and/or contralateral) invasive breast carcinoma or ductal carcinoma in situ.
• No history of any malignant neoplasms in the past 5 years except for curatively treated basal and squamous cell carcinoma of the skin.
• No history of serious cardiac illness or other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions. Baseline LVEF≥55% measured by echocardiography or MUGA scan (performed 2 weeks before randomization)

Eligibility Criteria at patient randomisation:

• ≥1CTC/15mL of blood by CellSearch® between 3 weeks and up to 12 weeks after surgery (neoadjuvant population) or end of adjuvant chemotherapy (adjuvant population).
• Centrally confirmed HER2-negative primary BC. Centralized HER2 testing will be performed in the surgical tumor specimen. A HER2-negative primary BC sample eligible for randomization should have HER2 IHC scores of 0 or 1+ or 2+ AND should be HER2 FISH negative in central testing.
• Baseline LVEF≥55% measured by echocardiography or MUGA scan (performed within 2 weeks prior to randomization)
• No evidence of unresolved or unstable serious toxicity from prior surgery, adjuvant chemotherapy or radiotherapy
• No concurrent participation in another trial.
• Written informed consent must be given according to ICH/GCP, and national/local regulations