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.
• •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.