MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I
MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I
Genomics assays that measure specific gene expression patterns in a patient's primary tumor
 have become important prognostic tools for breast cancer patients. This study is designed to
 test the ability of MammaPrint® in combination with TargetPrint®, BluePrint®, and
 TheraPrint®, as well as traditional pathologic and clinical prognostic factors, to predict
 responsiveness to neo-adjuvant chemotherapy in patients with locally advanced breast cancer
 (LABC).
Patients with suspected primary breast cancer on mammography and clinical examination will be
 assessed for eligibility by having a needle core biopsy to confirm invasive carcinoma.

 A fresh unfixed tumor specimen, incisional or core biopsy will be sent to Agendia to
 determine the MammaPrint risk profile, the BluePrint molecular subtyping profile, the
 TargetPrint ER, PR and HER2 single gene readout, the 56-geneTheraPrint Research Gene Panel
 and the additional genes as measured on the whole genome (44k) array.

 Surgical Protocol:

 1. Determination of nodal status:

 -  For clinically node-negative patients: Axillary ultra sound, followed by Sentinel
 Lymph Node (SLN) biopsy

 -  For clinically node-positive patients: ultra sound-guided Fine Needle Aspirate
 (FNA), followed by core biopsy

 2. Neo-adjuvant chemotherapy

 3. Definitive surgery:

 -  For node-positive patients: lumpectomy, repeat SLN biopsy, Axillary Lymph Node
 Dissection (ALND)

 -  For node-negative patients: lumpectomy, repeat SLN biopsy (optional), no ALND

 Response will be measured by pathological Complete Response (pCR) and by centrally assessed
 Residual Cancer Burden (RCB).
Inclusion Criteria:

 -  Women with histologically proven invasive breast cancer and no distant metastases and;

 -  Lymphnode negative and a clinical tumor classification of T2 (≥3.5cm)-T4 or with 1-3
 positive lymph nodes and a clinical tumor classification of T2-T4 DCIS or LCIS are
 allowed in addition to invasive cancer at T2 or T3 level.

 -  Age ≥ 18 years.

 -  At least one lesion that can be accurately measured in two dimensions utilizing
 mammogram, ultrasound, or MRI images to define specific size and validate complete
 pathologic response.

 -  Adequate bone marrow reserves (neutrophil count >1.5 x109 /l and platelet count >100
 x109/l), adequate renal function (serum creatinine ≤ 1.5 x upper limit of normal) and
 hepatic function (ALAT, ASAT ≤ 2.5 x upper limit of normal, alkaline phosphatase ≤ 2.5
 x upper limit of normal and total bilirubin ≤ 2.0 x upper limit of normal).

 -  Signed informed consent of the patient

 Exclusion Criteria:

 -  Any patient with confirmed metastatic disease. Patients with inflammatory breast
 cancer.

 -  Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails Quality Assurance
 or Quality Control 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.