NOSTRA-Feasibility Study: A Study Looking at Ultrasound Guided Biopsies for Breast Cancer

Inclusion Criteria:

• Patient with histological diagnosis of operable HER2-positive, ER-negative, earlystage 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 morethan five cycles of a NOSTRA-Feasibility Study approved treatment regimen, in theopinion 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 contraceptivemeasures if sexually active for at least 6 months after completion of studymedication

• 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 cytotoxicchemotherapy regimen

• Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion ofthe Investigator

• Prior diagnosis of cardiac failure

• Uncontrolled hypertension, coronary heart disease or other significant cardiacabnormality

• Bleeding diathesis

• Any evidence of other disease which in the opinion of the Investigator places thepatient at high risk of treatment related complications

• Pregnant (female patients of child bearing potential must have a urine or bloodHuman Chorionic Gonadotropin test performed to rule out pregnancy prior to studyentry)

• 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 theInvestigator 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 andstudy procedures

• Patient has started protocol non-compliant neo-adjuvant chemotherapy

• Patient has started approved neoadjuvant chemotherapy but insufficient data isavailable to complete relevant CRFs

• Patient has already received more than five cycles of approved neoadjuvantchemotherapy

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