Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.

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Many artists have used the symbol of salt in both religious and profane works, yet very few studies have explored the symbolism of salt as used in works of art. In this study, Panofsky’s method has been adopted to evaluate works of art through an organic process articulated into three stages: (1) pre-iconographic, (2) iconographic and (3) iconological. The method was used for (a) religious paintings of the Old and New Testaments and (b) mythological and profane themes. Various salt-cellars were also studied. In particular, the paper examines the following themes: Isaac blessing Jacob, the return of Esau, Samuel consecrating David, the Last Supper, the suppers at Emmaus and at the house of Simon, the birth of St. John the Baptist, the Baptism of Constantine, the prodigal son, Bacchus-Apollo, the nuptial banquet of Love and Psyche, the death of the Cavalier of Celano, the king drinks, the landlord’s visit, ‘Phitopolis faisant servir des mets en or au roi Pithès’, certain still life paintings and various salt-cellars including those of Cellini and Giulio Romano. The paper discusses the works of many artists including Raphael, Leonardo and his school (Boltraffio, Giampietrino, d’Oggiono, Solario), Hendricksz, Corenzio, Jean-Baptiste and Philippe de Champaigne, Damaskinos, Tintoretto, Titian, Romanino, Rubens, Bellini, Bloemaert, Veronese, Sustris, Just of Ghent, Jan Van Hemessen, Poussin, Loir, Giotto, Jordaens, Brueghel and Mimmo Paladino with his enchanted mountain. From the data examined it emerged that salt is a primary iconological presence in various works of art.

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