NBRST: Prospective Neo-adjuvant REGISTRY Trial

This will be a prospective observational, case-only study linking MammaPrint, BluePrint,
TargetPrint, TheraPrint and possible additional profiles of interest to treatment response
and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS). Only patients
who receive neo-adjuvant therapy can participate.

For this project, approximately 50-70 institutions in the US will be invited to contribute
clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and
TheraPrint test has been successfully performed and the patient has started neo-adjuvant
therapy.

Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a
recognized alternative.

The clinical data is to be entered online at 4 time points; amounting to four Case Report
Forms (CRFs). Data will be collected on an ongoing basis, the first CRF must be completed
within 6 weeks after the MammaPrint, BluePrint, TargetPrint, and TheraPrint result was
provided. The second CRF should be completed 4 weeks after definitive surgery. CRF 3 and CRF4
will be completed 2-3 and 5 years after surgery.

It is expected that we will enroll around 1000 patients in 4 years.

OBJECTIVES

- Measure chemosensitivity (as defined by pCR) or endocrine sensitivity (as defined by
decrease in longest tumor diameter or RCB1)in the molecular subgroups as determined by
combining MammaPrint and BluePrint results.

- Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.

- Compare local IHC and FISH results (if available) with TargetPrint results. Compare the
three BluePrint molecular subgroups with IHC-based subtype classification.

- Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.

- Assess the 2-3 and 5 years DMFS and RFS for the different molecular subgroups.

- Measure chemosensitivity or endocrine sensitivity correlation with novel expression
profiles.

Inclusion Criteria:

- Women with histologically proven breast cancer, who have started or are scheduled to
start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after
successful MammaPrint assay

- Age 18-90

- Written informed consent

Exclusion Criteria:

- Patients who have had excisional biopsy or axillary dissection Patients with confirmed
distant metastatic disease

- Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails QA or QC criteria

- Patients who have had any prior chemotherapy, radiotherapy, or endocrine therapy for
the treatment of breast cancer

- Any serious uncontrolled intercurrent infections, or other serious uncontrolled
concomitant disease