Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody–drug conjugates (ADCs) are a relatively new class of anticancer drugs. By merging the selectivity of monoclonal antibodies with the cytotoxic properties of chemotherapy, they improve the therapeutic index of antineoplastic agents. Three core components characterize ADCs: the antibody, directed to a target antigen; the payload, typically a cytotoxic agent; a linker, connecting the antibody to the payload. The most studied target antigen is HER2 with some agents, such as trastuzumab deruxtecan, showing activity not only in HER2-positive, but also in HER2-low BC patients, possibly due to a bystander effect. This property to provide a cytotoxic impact also against off-target cancer cells may overcome the intratumoral heterogeneity of some target antigens. Other cancer-associated antigens represent a strategy for the development of ADCs against triple-negative BC, as shown by the recent approval of sacituzumab govitecan. In this review, we discuss the current landscape of ADC development for the treatment of BC, as well as the possible limitations of this treatment.
Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.
17 August 2024 in Critical Reviews in Oncology/Hematology
Liquid biopsy has emerged as a crucial tool in managing breast cancer (BC) patients, offering a minimally invasive approach to detect circulating tumor biomarkers. Until recently, the majority of the studies in BC focused on evaluating a single liquid biopsy analyte, primarily circulating tumor DNA and circulating tumor cells (CTCs). Despite the proven prognostic and predictive value of CTCs, their low abundance when detected using enrichment methods, especially in the early stages, poses a significant challenge. It is becoming evident that combining diverse circulating biomarkers, each representing different facets of tumor biology, has the potential to enhance the management of patients with BC. This article emphasizes the importance of considering these biomarkers as complementary/synergistic rather than competitive, recognizing their ability to contribute to a comprehensive disease profile. The review provides an overview of the clinical significance of simultaneously analyzing CTCs and other biomarkers, including cell-free circulating DNA, extracellular vesicles, non-canonical CTCs, cell-free RNAs, and non-malignant cells. Such a comprehensive liquid biopsy approach holds promise not only in BC but also in other cancer types, offering opportunities for early detection, prognostication, and therapy monitoring. However, addressing associated challenges, such as refining detection methods and establishing standardized protocols, is crucial for realizing the full potential of liquid biopsy in transforming our understanding and approach to BC. As the field evolves, collaborative efforts will be instrumental in unlocking the revolutionary impact of liquid biopsy in BC research and management.