This study will assess whether a quantitative, HER2 assay can accurately and reliably discriminate between responders and non-responders among patients with HER2 IHCI+ metastatic breast cancer who are receiving T-Dxd.

Inclusion Criteria:

• Women and men age > 18 years
• Metastatic breast cancer, histologically- confirmed. Any estrogen receptor (ER) status is allowed. ER status will be determined by local laboratory assessment utilizing ASCO/CAP guidelines.
• Primary and/or metastatic tumor with 1+ level of expression of HER2 by immunohistochemistry as determined by local laboratory assessment utilizing ASCO/CAP guidelines.
• Measurable disease by cross-sectional imaging at the start of treatment. Patients with measurable bone-only disease or active brain metastases are eligible.
• Archival tissue available for biomarker assessment. One specimen should be the most recent metastatic biopsy. If HER2 1+ status was determined on a different specimen (either primary or metastatic tissue), that specimen is also required. Samples obtained from bone metastases that were processed via decalcification methods are not eligible.
• Intention to initiate therapy with T-DXd (Enhertu) at FDA-approved dose and schedule as next line of therapy. If T-DXd was already initiated, patients must be registered within 30 days of initiation.
• Ability to provide informed consent

Exclusion Criteria:

• Concurrent Her2-overexpressing metastatic breast cancer (as confirmed by a metastatic biopsy with IHC 3+ or IHC 2+ with FISH amplified as per standard ASCO/CAP guidelines)

Patients with HER2 IHC1+ metastatic breast cancer, histologically confirmed