RESUMEN
Antibody-drug conjugates (ADCs) represent an effective class of agents for the treatment of several tumor types, including breast cancer (BC), featuring approved molecules such as trastuzumab-emtansine, trastuzumab-deruxtecan, and sacituzumab-govitecan. Immune-checkpoint inhibitors (ICIs) also showed activity in selected BC subtypes, and two agents, pembrolizumab and atezolizumab, are currently approved for the treatment of triple-negative BC patients. The potential synergy between ADCs and immunotherapy in BC remains an area of active investigation. Preclinical studies suggest that ADCs promote immune surveillance, modulating tumor microenvironment, inducing immunogenic cell death, and enhancing antitumor immunity. Translational evidence has shown potential predictive biomarkers for ADCs alone or in combination with immunotherapy, including expression of target antigen, oncogenic pathways, tumor-infiltrating lymphocytes, and neutrophil-to-lymphocyte ratio. Given this background, several clinical trials evaluated ADC-ICI combinations in BC patients, demonstrating promising outcomes with an overall manageable toxicity profile, and many studies are currently ongoing to confirm the efficacy and feasibility of this therapeutic approach. In the present review, we summarized the available evidence about the integration of ADCs and immunotherapy for the management of BC, emphasizing the need for further translational and clinical investigations to optimize this treatment strategy and elucidate predictive biomarkers, eventually improving patient outcomes.
RESUMEN
Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously defined with different molecular profiles: (i) luminal androgen receptor (LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA). Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undefined prognosis and clinical behavior. Here, we report a case of a woman affected by recurring LAR TNBC, which underwent phenotypic changes throughout its natural history. After the initial diagnosis of LAR breast cancer, the patient experienced local recurrence with strong expression of the estrogen receptor. Due to this finding, she started treatment with a CDK4/6-inhibitor and an aromatase inhibitor, followed by oral vinorelbine, both with dismal outcomes. Then, she received everolimus and exemestane, which determined temporary disease stabilization. An extensive NGS analysis of tumor tissue showed PIK3CA and HER2 mutations. Our case is consistent with previous reports of LAR breast cancer and underlines the potential utility of re-biopsy and molecular testing in breast cancer (BC), especially in rare subtypes.