This multi-center observational prospective study will collect real-world clinical and patient-reported outcome data from eligible patients with unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2-based regimens or patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+, ISH-) breast cancer who have received at least a prior systemic therapy in the metastatic setting, or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

The primary objective of the study is to evaluate real-world time to next treatment or date of death from index date (T-DXd treatment initiation date)(rwTTNT) in each cohort. The secondary objectives of this study are to describe treatment patterns in eligible patients with HER2+ or HER2-low unresectable or mBC who are newly initiating T-DXd in a real-world setting, to describe demographic and clinical characteristics, to assess the safety and tolerability through the collection of physician-reported SEIs, to characterize the management of SEIs, to evaluate real-world time to treatment discontinuation (rwTTD) of T-DXd, and to evaluate patient-reported tolerability.

This decision to treat the patient with T-DXd will be made prior to, and independent of, their participation in this study. Eligible patients willing to participate will be enrolled consecutively in the study and followed up from index date (T-DXd treatment initiation date) until end of study, death, or withdrawal of consent, or loss to follow-up (LTFU), or study closure, whichever occurs first.

Patients must meet all of the following inclusion criteria to be eligible for the study:

1. ≥18 years of age at time of consent.

2. Pathologically documented breast cancer that is unresectable or metastatic.

3. Cohort A: Patients with confirmed HER2+ (IHC 3+ or IHC2+, ISH+); and patients have received one or more prior anti-HER2-based regimens; and patients should have received no more than 2 lines therapy in the metastatic settings.

   Cohort B: Patients with confirmed HER2-low expression (IHC 1+ or IHC 2+, ISH-); and patients have received at least a prior systemic therapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy; and patients should have received no more than 2 lines of previous chemotherapy regimen in the metastatic settings.

4. Decision to newly initiate T-DXd or just have started the first dose no longer than 14 days after the index date per approved label in China.

5. Capable of providing informed consent.

6. Patients capable of completing questionnaires are preferred. If the participant is unable to complete the questionnaire (e.g., being blind, illiterate, not fluent in the available language, or ePRO system is not ready), that participant is exempted from completing PRO questionnaires but may still participate in the study.

Patients who meet any of the following criteria will be excluded from the study:

1. Pregnancy or breastfeeding.
2. Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.
3. Patients who have known to have hypersensitivity reactions to the active substance of T-DXd or any excipients.
4. Patients who have been judged by the investigator to be unfit to participate the study.

Approximately 800 eligible subjects with HER2+ or HER2-low unresectable or mBC will be enrolled in this study.