Kadcyla In pAtients With bRAin Metastasis

Inclusion Criteria: Participants must meet all these criteria in order to be eligible for the study: General Criteria: * Female patients (≥ 18 years); * Histologically confirmed HER2-positive breast cancer patients (IHC 3+ and/or ISH positive); * Patients should have previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy; * At least one measurable brain metastasis as defined by RECIST 1.1 (≥ 10 mm); * Any hormone receptor status; * Predicted life expectancy \> 3 months; * Any previous anti-HER2 therapies are allowed, other than T-DM1; * ECOG performance score 0-2; * No significant cardiac history and a current LVEF ≥ 50%. LVEF should be determined within 21 days before enrolment; * Adequate organ function, evidenced by the following laboratory results. Exams are to be performed at a maximum of 7 days before enrolment. * Absolute neutrophil count \> 1,500 cells/mm3 without growth factor support (14 days after last peg-filgrastrim, 7 days for regular filgrastrim). * Platelet count \> 100,000 cells/mm3 without transfusion 2 weeks prior assessment * Hemoglobin \> 9 g/dL without transfusion 2 weeks prior assessment. * Aspartate aminotransferase and alanine aminotransferase \< 2.5 x upper limit of normal (ULN). * Total bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert's syndrome, in which case direct (conjugated) bilirubin level needs to be within normal limits. * Serum alkaline phosphatase ≤ 2.5 x ULN. Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN. * Serum creatinine \< 2.0 mg/dL or \< 177 μmol/L. * International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time \< 1.5 ULN unless patient receiving anticoagulant therapy * For women of childbearing potential a serum pregnancy test will be done up to 7 days before enrolment (and it must be negative) and an agreement to use one highly-effective form of non-hormonal contraception (true abstinence, vasectomy, oophorectomy/hysterectomy, IUD) or two effective forms of non-hormonal contraception (e.g., condoms plus spermicidal agent) at study entry (to be put in place within 2 weeks prior to enrolment), during the administration of T-DM1 and for 7 months after the last administration of T-DM1 will be obtained * Signed informed consent obtained before any study-specific procedure; * Able and willing to comply with the protocol; including the willingness to provide samples (primary if available and blood) for translational research. Cohort 1 additional specific criteria: * No corticosteroids at enrolment * Oligosymptomatic or asymptomatic brain metastases not requiring immediate local therapy. Cohort 2 additional specific criteria: * Radiologically confirmed brain progression after previous local therapy (neurosurgery, radiosurgery to the brain, stereotactic radiotherapy to the brain, or whole brain radiotherapy) with at least 3 months between end of local therapy and brain progression. * Decreasing corticosteroid dose or stable dose for at least one week prior to enrolment Exclusion Criteria: Patients who exhibit any of the following conditions at screening will be ineligible for admission into the study: General Criteria: * Single brain metastasis with indication of surgical resection * Pregnant or breast-feeding women * Documented leptomeningeal disease * Having received any investigational therapy within ≤ 28 days or 5 half-lives at ICF signature, whichever is longer * Having received hormonal therapy within 14 days of enrolment * Having received trastuzumab within 21 days of enrolment * Prior enrolment in a T-DM1-containing study, regardless of whether the patient received T-DM1 or not * History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product. * Current peripheral neuropathy of Grade ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0.3 * History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above. * Current unstable ventricular arrhythmia requiring treatment. * History of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] Classes II-IV). * History of myocardial infarction or unstable angina within 6 months prior to first study drug administration. * Current dyspnoea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy. * Current severe, uncontrolled systemic disease other than cancer (e.g., clinically significant pulmonary, hypertension or metabolic disease) * Concurrent, serious, uncontrolled infections or current known infection with HIV, active hepatitis B and/or hepatitis C. * Major surgical procedure or significant traumatic injury within 28 days before enrolment or anticipation of the need for major surgery during the course of study treatment. * Known contraindications for undergoing MRI or CT, including to receive contrast media, Cohort 1 : additional specific criteria: • Previous neurosurgery or radiotherapy (radiosurgery, stereotactic radiotherapy, whole brain radiotherapy) to the brain Cohort 2 : no additional specific criteria