Trastuzumab deruxtecan (T-DXd) as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

Based on the extended therapeutic indication of Trastuzumab deruxtecan (Enhertu®), a new patient population will be enrolled, comprising adult patients with unresectable or metastatic HR-positive, HER2-low, or HER2-(ultra)low breast cancer who have received at least one endocrine therapy in the metastatic setting and are not considered suitable for endocrine therapy as the next line of treatment.

This non-interventional study will investigate the effectiveness of T-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low and HER2-(ultra)low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study.

Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study. For Study Group 2, only baseline data will be collected for patients treated with conventional chemotherapy.

Inclusion Criteria:

Study Group 1 and Study Group 2

• Adult patient (age ≥ 18 years) with histological or cytological confirmed diagnosis of unresectable and/or mBC
• Decision to newly initiate therapy of T-DXd or conventional chemotherapy according to the physicians choice per SmPC
• Written and signed Informed Consent to participate in the study

Study Group 1

• Documented HER2-low status (IHC1+, IHC2+/ISH-)
• Patients who have received prior chemotherapy in the metastatic setting or
• Patients who have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

Study Group 2:

• Documented HR+ status
• Documented HER2-low status (IHC1+ or IHC2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining [IHC > 0 to <1+]) status
• Patients who have received at least one endocrine therapy in the metastatic setting
• Patients who have NOT received prior chemotherapy in the metastatic setting

Exclusion Criteria:

Study Group 1 and Study Group 2

• Pregnancy or breastfeeding
• Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.

No other specific exclusion criteria are defined, as patients will be treated according to the proposed indication statements in the SmPC.

Study Group 1 will include adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

Study Group 2 will include adult patients with unresectable or metastatic HR +, HER2-low and HER2- ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment and have not received prior chemotherapy for advanced metastatic breast cancer.