HER2-positive Breast Cancer With Brain Metastasis (GCC 1345)

Inclusion Criteria:

* Histologically proven diagnosis HER2-positive breast cancer. Her2-positive is defined as follows:

  \* Validated IHC assay score of 3+ (defined as uniform, intense staining of \>30% of invasive tumor cells)
* OR- Average HER2 gene copy number of \>6
* OR- Gene amplified (HER2:D17Z1 ratio \>2.20).
* Patients with 1-10 newly diagnosed brain metastases
* The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.
* History and physical with neurological examination, steroid documentation, height, and weight within 14 days of registration.
* A diagnostic contrast-enhanced MRI of the brain must be performed within 28 days prior to registration.
* Eligibility for treatment with SRS confirmed by a radiation oncologist.
* Performance Status 0-2
* Age ≥ 18.
* CBC with differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) ≥ 1,100 cells/mm3.
* Platelets ≥ 75,000 cells/mm3.
* Hemoglobin ≥ 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥9.0 g/dl is acceptable).
* Adequate renal function within 14 days prior to registration, as defined below:
* BUN ≤ 30 mg/dl.
* Creatinine ≤ 1.5 x ULN
* Creatinine clearance ≥30 mL/min.

Adequate hepatic function within 14 days prior to registration, as defined below:

* Total Bilirubin ≤1.5 x ULN
* ALT/AST ≤ 2.5 x upper limit of normal (ULN).
* Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to registration.
* Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 14 days prior to registration. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:
* No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
* In-range INR (between 2.5 and 3.5) on a stable dose of warfarin-based oral anticoagulant; or on a stable dose of low molecular weight heparin; or INR between 1.5 and 2 if a Greenfield filter is in place.
* Patient must provide study specific informed consent prior to study entry.
* For women of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.
* Women of childbearing potential and male participants must practice adequate contraception.
* Echocardiogram or MUGA scan with ejection fraction within normal institution limits within 28 days of registration

Exclusion Criteria:

* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. For example, carcinoma in situ of the oral cavity and cervix are all permissible.
* Leptomeningeal metastases
* Previous treatment with all of the following: lapatinib, trastuzumab, pertuzumab, and trastuzumab emtansine. (Patients are eligible if treated with 3 or less of these agents.)
* Prior cranial radiotherapy.
* Prior resection of cerebral metastases
* Allergy to gadolinium

Severe, active co-morbidity, defined as follows:

* Unstable angina and/or congestive heart failure within the last 6 months.
* Transmural myocardial infarction within the last 6 months.
* New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
* History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months.
* Serious and inadequately controlled cardiac arrhythmia.
* Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
* Evidence of bleeding diathesis or coagulopathy.
* Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess, major surgical procedure or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection or follow-on craniotomies to manage complications of brain tumor management such as hemorrhage or infection.
* Bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
* Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
* Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
* Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.
* Women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the chemotherapeutic treatment involved in this study is potentially teratogenic.
* Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study treatment.
* Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
* Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker).
* Inability to undergo SRS due to claustrophobia