Neoadjuvant Phase II Trial in Patients With T1c Operable, HER2-positive Breast Cancer According to TOP2A Status

Inclusion Criteria:

* Women aged ≥ 18;
* Patient has histologically confirmed breast cancer, with a clinical tumour diameter of \> 1 cm (cT1c, cT2-3 or T4a)-
* Any N status
* No clinically or radiologically detectable metastases (M0);
* HR negative (both ER and PR \< 10% by IHC); for T1c status, otherwise HR negative or positive
* Her-2 positive (i.e. IHC score 3+ or FISH/SISH/CISH positive);
* Performance status ≤ 1 (according to WHO criteria);
* Patients not previously treated by surgery, radiotherapy, hormone therapy or chemotherapy;
* Hæmatology: Absolute neutrophil count (ANC) ≥1,500/mm³; Platelets ≥100,000/mm³; Total white blood cell count (WBC) ≥3.000/mm³; Hb\> 9g/dl;
* Hepatic Function: Total bilirubin ≤1.5 time the upper normal limit (UNL); ASAT ≤ 1.5xUNL; ALAT ≤ 1.5xUNL; Alkaline phosphatase ≤ 2.5xUNL;
* Renal Function: Serum creatinine ≤1.5xUNL (and if Serum creatinine \>1.5xUNL, Creatinine clearance ≥50 mL/min (MDRD formula);
* Metabolic Function: Magnesium ≥ lower limit of normal; Calcium ≥ lower limit of normal;
* Patient with not controlled heart disease and for whom anthracyclines are not contraindicated. Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion;
* Patient agreeing to use effective contraception during and for ≥ 7 months after completion of study treatment;
* Patient able to comply with the protocol;
* Patient must have signed a written informed consent form prior to any study specific procedures;
* Patient must be affiliated to a Social Health Insurance.

Exclusion Criteria:

* Bilateral or multifocal breast cancer;
* Non-measurable tumour;
* Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or overlooked forms (T4b or T4d);
* HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative);
* RH positive (ER or PR ≥ 10% by IHC) ;
* Patient has a history of second cancer, with exception of in situ cervical cancer or basocellular skin cancer which is regarded as cured;
* Patient has already been treated for new breast cancer;
* Patients have already undergone surgery for their disease or have had primary axillary dissection;
* Prior docetaxel administration or anti-HER2 antibody therapy (e.g.: trastuzumab or pertuzumab);
* Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:

  * Heart or kidney failure, medullary, respiratory or liver failure, dyspnea
  * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, poorly controlled hypertension) ≤ 1 year before enrollment
  * Uncontrolled diabetes
  * Significant neurological or psychiatric abnormalities
  * Symptomatic or progressive disorder of the central nervous system (CNS) or metastasis at the initial check-up.
  * Peripheral neuropathy \> grade 2
  * Acute urinary infection, ongoing hemorrhagic cystitis;
* Patients with a known history of HIV seropositivity;
* Sensitivity to any of the study medications or any of the ingredients or excipients of these medications;
* Patients receiving of the concomitant medications with phenytoin;
* Patients who received any other investigational drugs within 30 days of initiation of treatment and/or during the study;
* Must not have had a major surgical procedure within 30 days of initiation of treatment;
* Pregnant women, women who are likely to become pregnant or are breast-feeding;
* Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
* Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol;
* Individual deprived of liberty or placed under the authority of a tutor.