The Double-edged Sword of Targeted Therapy: Trastuzumab Deruxtecan-induced Interstitial Lung Disease in Breast Carcinoma: A Case with Review

Case DesCriptionA 66-year-old female, a homemaker with a history of well-controlled hypertension and hypothyroidism, presented to our institute in April 2023 with complaints of a progressively enlarging right breast lump.On clinical examination and biopsy, she was diagnosed with invasive ductal carcinoma, grade 3, estrogen receptor (ER) and progesterone receptor (PR) negative, and HER2-positive, introDuCtion Breast cancer remains the most common malignancy among women worldwide, with human epidermal growth factor receptor (HER2) positivity reported in approximately 15-20% of cases and associated with aggressive disease biology and poorer prognosis. 1 The advent of HER2-targeted therapies has significantly improved survival outcomes in this subgroup.Trastuzumab deruxtecan (T-DXd), a novel antibody-drug conjugate (ADC), combines a humanized anti-HER2 monoclonal antibody with a cleavable linker and a potent topoisomerase I inhibitor payload (deruxtecan). 2This unique design provides not only direct cytotoxicity but also a "bystander effect," enabling activity even in HER2-low tumors. 3 While T-DXd has transformed the therapeutic landscape in HER2-positive and HER2-low metastatic breast cancer, it carries a distinct toxicity profile.The most concerning adverse event is interstitial lung disease (ILD)/ pneumonitis, which can be life-threatening.Across pivotal trials such as DESTINY-Breast01, 03, and 04, ILD incidence has ranged between 9 and 15%, with fatal cases reported despite proactive monitoring. [4]5][6] The risk appears to be dose-dependent and typically emerges within the first year of therapy.Recognizing clinical and radiological features early, excluding infectious or malignant differentials, and instituting prompt corticosteroid therapy are essential to improving outcomes. 7 We report here a case of T-DXd-associated ILD in a patient with stage IV right breast carcinoma, highlighting the diagnostic and management challenges, followed by a review of the literature.