PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial

Inclusion Criteria: * Previously untreated, histologically confirmed non-inflammatory breast cancer, \>4 cm in diameter and /or metastatic ipsilateral axillary deposits for which the smallest diameter of the largest node \>2 cm by CT or ultrasound scan. * WHO performance status 0-1 * Known tumor ER, PGR, HER2 and TP53 status. * Known tumor Ki67 percentage (if ER/PGR\>50% and TP53 wt status). * Distant metastasis not suspected. Patients will undergo radiology exams during screening phase, after signing the informed consent. * Age \>18 years * Patients must have clinically and/or radiographically documented measurable breast cancer according to RECIST. * Radiology studies (CT thorax/abdomen and bone scintigraphy/bone scan) must be performed within 28 days prior to registration. * Absence of 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 * Before patient registration/randomization, written informed consent must be given according to national and local regulations. * For arms B-H: * Neutrophils \> 1.5 x 109/L * Platelets \> 100 x 109/L * Bilirubin \< 2 x upper limit normal (ULN). For patients with Gilbert´s syndrome bilirubin \>2 x ULN is accepted if there is no evidence of biliary obstruction. * Serum creatinine \< 1.5 x ULN * ALT and Alk Phos (ALP) \<2.5 x ULN * INR \< 1.5 Exclusion Criteria: * Unstable angina pectoris or heart failure * Other co-morbidity that, based on the assessment of the treating physician, may preclude the use of chemotherapy at actual doses. * Pregnant or lactating patients can not be included. * Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist. * Patient not able to give an informed consent or comply with study regulations as deemed by study investigator. * Active cystitis (to be treated upfront) * Active bacterial infections * Urinary obstruction