Antibody-drug conjugates (ADCs) are a class of targeted cancer therapies designed to deliver cytotoxic drugs directly to tumor cells whereas sparing healthy tissue. In breast cancer treatment, ADCs have emerged as a significant advancement, particularly for patients with HER2-positive, HER2-low, and hormone receptor-positive metastatic disease. These therapies combine the specificity of monoclonal antibodies with the potency of chemotherapy, enabling precise delivery of anticancer agents to cancer cells expressing specific antigens. The development and clinical use of ADCs in breast cancer have been informed by robust clinical trial data. Trastuzumab deruxtecan (T-DXd), for example, is an ADC approved for the treatment of HER2-low metastatic breast cancer, a population previously considered ineligible for HER2-targeted therapies. Clinical trials such as DESTINY-Breast04 demonstrated that T-DXd significantly improved progression-free and overall survival compared to chemotherapy in this subgroup, leading to regulatory approval and changes in treatment guidelines. Another ADC, sacituzumab govitecan, targets Trop-2 and is approved for metastatic triple-negative breast cancer and hormone receptor-positive, HER2-negative breast cancer. Trials including ASCENT and TROPiCS-02 have shown meaningful improvements in survival outcomes for patients who have received prior therapies, establishing sacituzumab govitecan as a key option in later-line treatment. Despite their efficacy, ADCs carry specific safety considerations. Interstitial lung disease (ILD) is a known class effect, particularly associated with T-DXd, with reported incidence rates ranging from 12% to 15% across studies. This risk necessitates proactive monitoring, including baseline and periodic imaging, along with patient education on respiratory symptoms such as cough or dyspnea. Early detection and prompt intervention, including corticosteroid use and treatment discontinuation when necessary, are critical to managing this adverse event effectively. Clinical decision-making around ADC use involves evaluating prior treatment history, biomarker status (such as HER2 expression levels), comorbidities, and patient preferences. Sequencing of ADCs—using one ADC after another—remains an area of active investigation, as current evidence does not strongly support routine sequential use due to overlapping toxicities and limited data on efficacy in later settings. Ongoing research aims to identify optimal sequences, biomarkers of response, and strategies to mitigate resistance. Adverse event management is integral to ADC therapy. Common side effects include nausea, fatigue, alopecia, and neutropenia, which are generally manageable with supportive care. Proactive symptom assessment, dose adjustments, and timely interventions help maintain treatment continuity and quality of life. As research progresses, next-generation ADCs are being developed with improved linkers, payloads, and targeting mechanisms to enhance efficacy, and safety. Novel targets such as HER3, B7-H3, and folate receptor alpha are under investigation, aiming to expand the applicability of ADCs across breast cancer subtypes and earlier lines of therapy. The integration of ADCs into breast cancer care reflects a broader shift toward precision oncology, where treatment is tailored to the molecular profile of the tumor and the individual patient. By combining target specificity with potent cytotoxic activity, ADCs represent a valuable tool in the evolving landscape of breast cancer management, offering meaningful clinical benefits when used appropriately and monitored closely.
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