The researchers doing this study think that performing scans of the brain and testing cerebrospinal fluid (CSF) in people with HER2-positive breast cancer may be an effective way of identifying the early onset of CNS metastases (such as brain cancer). If the researchers can identify the early onset of CNS metastases, they can immediately treat that cancer and possibly prevent it from worsening. Currently, people with breast cancer don't usually have scans of the brain or CSF testing unless they are experiencing symptoms of CNS metastases.

Inclusion Criteria:

• Patients with Stage IV metastatic HER2+ breast cancer without CNS disease s/p 1 or more lines of HER2 directed therapy (Cohort A Only)
• Patients with Stage II-III HER2+ breast cancer without CNS disease (Cohort B Only)
• Male and Female participants Age ≥18 years
• HER2+ as defined by ASCO/CAP guidelines*
• Ability to undergo bedside Lumbar puncture to obtain cerebrospinal fluid; if beside LP is not successful due to patient discomfort or inability to obtain spinal fluid then patients will be offered LP through interventional radiology and patients will continue to be monitored on study
• Patients with breast implants and/or tissue expanders are eligible if they are able to safely undergo an MRI
• Able to provide written informed consent *ASCO/CAP guidelines: HER2+ defined as IHC 3+ positive and/or by ISH average copy number ≥ 6 signals/cell

Exclusion Criteria:

• Patients who are unable to undergo MRI with gadolinium
• Patients with CNS Metastases on Screening MRI
• Patients with Positive Cytology on Screening Bedside lumbar puncture

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.