Megestrol Acetate for Fatigue Management in T-DXd Treated Breast Cancer

This study aims to evaluate whether the combination of Megestrol Acetate at the initiation of Trastuzumab Deruxtecan (T-DXd) treatment can effectively prevent and alleviate T-DXd-related fatigue, thereby improving the quality of life for advanced breast cancer patients.

Evaluate the efficacy and safety of Megestrol Acetate (MA) in improving fatigue in breast cancer patients after T-DXd treatment.

Inclusion Criteria: 1. Female, aged 18-75 years 2. Pathologically confirmed inoperable or metastatic breast cancer with complete ER, PR, and HER2 status 3. HER2-positive (IHC 3+ or IHC 2+ with FISH positive), HER2-low (IHC 1+ or IHC 2+ with FISH negative), or HER2-ultralow (IHC 0 with ≤10% weak incomplete membrane staining) \[most recent specimen used\] 4. Investigator-assessed indication for Trastuzumab Deruxtecan (T-DXd) therapy 5. No prior treatment with Trastuzumab Deruxtecan 6. Received ≤5 lines (including 5 lines) of prior chemotherapy 7. ECOG Performance Status 0-1 8. Estimated life expectancy ≥12 weeks 9. Adequate organ function 10. Reliable contraception or negative serum/urine pregnancy test within 7 days prior to enrollment; willing to use appropriate contraception during study and for 8 weeks after last dose 11. Voluntary participation with good compliance Exclusion Criteria: 1. Severe underlying disease, comorbidities, active infection, or severe metabolic disorders 2. Clinically significant severe fatigue at baseline (FACIT-F score \<30) 3. Currently receiving other antitumor therapies 4. Pregnant or lactating patients 5. Poor compliance or unable to complete normal follow-up 6. History of allergy to megestrol acetate or other components of the formulation 7. History of thromboembolism (use with caution) 8. Other malignancies diagnosed within 5 years, except: resected non-melanoma skin cancer, adequately treated cervical carcinoma in situ, locally radically treated prostate cancer, surgically radically treated ductal carcinoma in situ, or malignancies diagnosed \>2 years ago with no current disease evidence and untreated for ≤2 years before randomization 9. Any condition judged by investigator that may affect study conduct or outcome assessment