Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

Inclusion Criteria:

* Histologically confirmed infiltrating breast cancer
* Stage II or stage III disease. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan.
* Overexpression and/or amplification of HER2 in an invasive component of the core biopsy, according to one of the following definitions:

  •\>30% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+)

  •HER2 gene amplification defined as \>6 HER2 gene copies per nucleus by in situ hybridization.
* Age ≥18
* Eastern Cooperative Oncology Group performance status ≤1
* Adequate bone marrow function (ANC \>1.5 x 109/l, platelets \>100 x 109/l)
* Adequate hepatic function (ALAT, ASAT and bilirubin \<2.5 times upper limit of normal)
* Adequate renal function (creatinine clearance \>50 ml/min)
* LVEF ≥50% measured by echocardiography or MUGA
* Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Absence of any medical condition that would place the patient at unusual risk.
* Signed written informed consent

Exclusion Criteria:

* previous radiation therapy or chemotherapy
* other malignancy except carcinoma in situ, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiation therapy.
* current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection
* evidence of distant metastases. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures.
* evidence of bilateral infiltrating breast cancer. Evaluation of the presence of bilateral infiltrating breast cancer may include mammography, breast ultrasound and/or MRI breast.
* concurrent anti-cancer treatment or another investigational drug.