Recurrent breast cancer complicated by T-DXd-associated dermatomyositis and interstitial lung disease

What happened, in summary

This 43-year-old Chinese woman had no personal or family history of autoimmune disease when she was diagnosed in December 2022 with left invasive ductal breast carcinoma. The initial tumor was weakly ER-positive at 20%, PR-negative, AR weakly positive at 10%, HER2 0, mutant p53-positive at 90%, and highly proliferative with Ki-67 80%. She underwent left modified radical mastectomy. Frozen section showed a small metastatic deposit in the sentinel lymph node, while left axillary nodes were negative. Starting in January 2023, she received adjuvant AC-T chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel liposome. She also received tamoxifen plus goserelin and radiotherapy to the chest wall and supraclavicular region, 48 Gy in 25 fractions. In March 2024, the disease progressed with multiple lymph-node metastases and was staged cT2N3cM0, Stage IIIC. Biopsy of a left supraclavicular lymph node showed a more aggressive recurrent profile: ER-negative, PR-negative, AR-negative, HER2 mostly 0 with low-level 1+/2+ staining, mutant p53-positive 80%, Ki-67 90%, TROP-2 3+, and PD-L1 CPS about 30. She received gemcitabine plus carboplatin, but the cancer progressed after 6 cycles. Trastuzumab deruxtecan began in November 2024. Seven days after the first infusion, she developed itchy widespread rash that evolved into classic dermatomyositis signs, including heliotrope rash, Gottron papules, neck/chest poikiloderma, proximal weakness, and muscle pain. Prednisone initially helped, but after further trastuzumab deruxtecan exposure her dermatomyositis worsened, and CT showed interstitial pneumonia. The course raised concern for a serious drug-related immune complication, although paraneoplastic dermatomyositis could not be excluded during ongoing cancer treatment.