Inclusion Criteria:
1. Male or female aged \>18 years at the time of consent
2. Breast cancer with progressive brain metastases supra and/or infratentorial. Patients can proceed with SRS as long as at least 1 lesion which is 2 cm or less in a noncritical area in the brain is spared as per the discretion of treating neurosurgeon/radiation oncologist.
3. At least one non irradiated, untreated progressive brain metastases site
4. Serum HCMV DNA by real time PCR \> 250 copies/ml or positive CMV Ig G or Ig M.
5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. If the patient is unable to consent for any reason a legally authorized guardian may provide consent on their behalf. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) will be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
6. Metastatic breast cancer who has systemically no evidence of disease, complete remission, partial remission, stable or progressive disease
7. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
8. Adequate hematology without ongoing transfusion support (hemoglobin \> 9 g/dl, absolute neutrophil count (ANC) \> 1500 per mm3 , platelets \> 100,000 per mm3)
9. Adequate renal and hepatic function (creatinine clearance \[CrCL\] \> 60 mL/min, bilirubin x:≤1.5 upper limit of normal (ULN), aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] ≤ 2.5 x ULN and serum albumin ≥ 3 g/dl.
10. Other CMV treatment if clinically indicated per physician's choice
11. Evidence of postmenopausal status or negative serum pregnancy test for premenopausal female patients. Negative serum β-human chorionic gonadotropin pregnancy test within 7 days prior to the first dose of study treatment for premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause.
The following age-specific requirements apply:
12. Women \<50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
13. Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
14. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
Exclusion Criteria:
1. Single resectable intracranial lesion
2. Last intracranial progression free survival \> 12 months
3. All progressive brain metastases have been radiated
4. Brain metastases needing immediate local intervention such as mass effect, herniation, active neurological symptoms, increased intracranial pressure, those near vital structures like the motor cortex, proximity to the optic nerve/chiasm or brain stem etc (can still be included if there are any other non-radiated progressive brain metastases) Multidisciplinary discussion with neurosurgery and radiation oncology will be needed to determine which patients may be safely enrolled on the trial.
5. Active pregnancy or breast feeding
6. Women of childbearing potential or fertile men unwilling to use effective contraception (Section 6.2, Table 6) during study and up to three months after treatment discontinuation.
7. Known psychiatric disorder that causes poor cooperation with the trial requirements.
8. Participants with previous other malignancies must have had at least a 3-year disease free interval, except those with non-melanoma skin cancer or carcinoma in situ of cervix
9. Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.
10. Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
11. Unresolved or unstable adverse events (AEs) from prior administration of another investigational drug, per investigators' discretion.
12. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.
13. Non-English-speaking subjects will not be enrolled in this study since the neurocognitive tests including DKEFS, RAVLT and TMT are not validated to be scored in other languages.
