Atezolizumab + Pertuzumab + Trastuzumab In CNS Mets In BC

Inclusion Criteria:

\- Eligibility will be assessed as part of the screening procedures for all patients.

* Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ≥ 2.0 or average HER2 copy number ≥ 6.0 signals/cells).
* At least one measurable CNS metastasis, defined as ≥ 10 mm in at least one dimension
* Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:

  * Treated with SRS or surgery with residual un-treated lesions remaining. Such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable
  * Participants who have had prior WBRT and/or SRS and then whose lesions have subsequently progressed are also eligible. In this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS.
  * Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control.
  * Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (echo) or multigated acquisition (MUGA) scan within 28 days before day 1 of study.
* Stable dose of dexamethasone 2mg or less for at least 7 days prior to initiation of treatment
* Concurrent administration of other anti-cancer therapy during the course of this study is not allowed. Note that concurrent use of supportive care medications (e.g. anti-resorptive agents, pain medications) is allowed.
* The subject is 18 years old.
* Participants must have normal organ and marrow function as defined below:

  * absolute neutrophil count ≥1,000/μl
  * platelets ≥75,000/μl
  * hemoglobin ≥9 g/dL
  * total bilirubin ≤1.5mg/dL (upper limit of normal) except subject with documented Gilbert's syndrome (≤5 x ULN) or liver metastasis, who must have a baseline total bilirubin ≤3.0 mg/dL;
  * AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN ≤ 5.0 × institutional ULN for patients with documented liver metastases.
  * albumin \>2.5mg/dL
  * serum creatinine ≤ 1.5 mg/dL (or glomerular filtration rate ≥ 60 ml/min as determined by the Cockcroft-Gault equation)
* Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 8 days of initiating protocol therapy.
* The effects of atezolizumab on the developing human fetus are unknown and radiotherapy has known teratogenic effects so women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of atezolizumab administration.
* The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

Exclusion Criteria:

* Visceral crisis or impending visceral crisis at time of screening.
* CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement).
* Known leptomeningeal or brainstem metastases \[Defined as positive CSF cytology and/or unequivocal radiological evidence of clinically significant leptomeningeal involvement. CSF sampling is not required in the absence of suggestive symptoms to exclude leptomeningeal involvement\].
* Treatment with high dose systemic corticosteroids defined as dexamethasone \> 2mg/day or bioequivalent within 7 days of initiating therapy.
* Patients unable to undergo gadolinium contrast-enhanced MRI or receive IV contrast for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitivity).
* Chemotherapy or targeted therapy within 14 days prior to cycle 1 day 1 of protocol therapy.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
* No washout is required for endocrine therapy. If a patient has been on endocrine therapy within 28 days of study entry, that same endocrine therapy is permitted to be continued during protocol therapy, at the investigator's discretion, as is continuation of ovarian suppression in premenopausal women. Starting a new endocrine therapy during protocol therapy is not permitted
* Current use or history of receiving a non-approved, investigational treatment within 14 days prior to cycle 1 day 1 of protocol therapy
* Subjects with a history of hypersensitivity to compounds of similar biologic composition to atezolizumab or any constituent of the product
* The subject has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, or severe malnutrition.
* The subject is pregnant or breast-feeding
* No active, second potentially life-threatening cancer
* Has had major surgery within 21 days before cycle 1, day 1
* Active infection requiring iv antibiotics at day 1 of cycle 1
* Participant has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
* The participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with atezolizumab.
* Has received a live vaccine within 28 days of planned start of study therapy.
* Known intolerance to trastuzumab or pertuzumab or atezolizumab.