A prospective non-randomised multi-centre feasibility study to assess if patients with residual cancer following dual-targeted neoadjuvant chemotherapy treatment for HER2-positive, ER-negative early breast cancer can be identified by multiple ultrasound (US)-guided tumour bed core biopsies

The NOSTRA-Feasibility study is designed to determine if it is safe to omit surgery after the planned neoadjuvant chemotherapy plus dual-targeted anti-HER2 treatment. The study is needed to determine whether patients with residual cancer can be identified by histological examination of multiple ultrasound-guided tumour bed core biopsies following dual-targeted neoadjuvant treatment for HER2-positive, ER-negative early primary breast cancer and whether there is concordance between local pathology reporting and central pathology reporting by the trials expert pathologists.

Inclusion Criteria:

• Patient with histological diagnosis of operable HER2-positive, ER-negative, early stage invasive breast cancer
• Tumour size ≥ 1cm and visible on US (T1c to T4d)
• Patient fit and willing to receive, or is already receiving and has received no more than five cycles of a NOSTRA-Feasibility Study approved treatment regimen, in the opinion of the responsible clinician
• Eastern Co-operative Group (ECOG) performance status of 0 or 1
• Women of child-bearing potential, prepared to adopt highly effective contraceptive measures if sexually active for at least 6 months after completion of study medication
• Female, 18 years or older
• Able to provide informed consent for the study
• Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy
• The radiology team are able and willing to perform the tumour bed core biopsies

Exclusion Criteria:

• Previous ipsilateral invasive breast cancer or Ductal Carcinoma in Situ (DCIS)
• Unequivocal evidence of distant metastatic disease at registration
• Multi-focal disease at diagnosis
• Active malignancy
• Previous chemotherapy
• Prior extensive radiotherapy (as judged by the Investigator) to bone marrow
• Risk factors precluding the safe administration of the intended cytotoxic chemotherapy regimen
• Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion of the Investigator
• Prior diagnosis of cardiac failure
• Uncontrolled hypertension, coronary heart disease or other significant cardiac abnormality
• Bleeding diathesis
• Any evidence of other disease which in the opinion of the Investigator places the patient at high risk of treatment related complications
• Pregnant (female patients of child bearing potential must have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to study entry)
• Patient lactating
• Patients who have received live vaccine within 4 weeks of the date of study entry
• Any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment or follow-up
• Patient unfit and/or unwilling to undergo surgery
• Patient unwilling or unable to comply with scheduled visits, treatment plan and study procedures
• Patient has started protocol non-compliant neo-adjuvant chemotherapy
• Patient has started approved neoadjuvant chemotherapy but insufficient data is available to complete relevant CRFs
• Patient has already received more than five cycles of approved neoadjuvant chemotherapy

Additional Inclusion Criteria for ctDNA Sub-Study

• Patient has not yet started neoadjuvant treatment
• Patient is willing and able to give blood samples as per ctDNA Sub-Study Guidelines

HER-2 positive ER-negative breast cancer patients