ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.

HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

BACKGROUND: HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. PATIENTS AND METHODS: Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. RESULTS: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab. CONCLUSIONS: Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. TRIAL REGISTRATION: ISRCTN Register: 99828560.

King of the Renaissance: Art and Politics at the Neapolitan Court of Ferrante I, 1458-1494

In the second half of the fifteenth century, King Ferrante I of Naples (r. 1458-1494) dominated the political and cultural life of the Mediterranean world. His court was home to artists, writers, musicians, and ambassadors from England to Egypt and everywhere in between. Yet, despite its historical importance, Ferrante’s court has been neglected in the scholarship. This dissertation provides a long-overdue analysis of Ferrante’s artistic patronage and attempts to explicate the king’s specific role in the process of art production at the Neapolitan court, as well as the experiences of artists employed therein. By situating Ferrante and the material culture of his court within the broader discourse of Early Modern art history for the first time, my project broadens our understanding of the function of art in Early Modern Europe. I demonstrate that, contrary to traditional assumptions, King Ferrante was a sophisticated patron of the visual arts whose political circumstances and shifting alliances were the most influential factors contributing to his artistic patronage. Unlike his father, Alfonso the Magnanimous, whose court was dominated by artists and courtiers from Spain, France, and elsewhere, Ferrante differentiated himself as a truly Neapolitan king. Yet Ferrante’s court was by no means provincial. His residence, the Castel Nuovo in Naples, became the physical embodiment of his commercial and political network, revealing the accretion of local and foreign visual vocabularies that characterizes Neapolitan visual culture.

The importance of being Alfred -- from the king of West Saxons to Nobel

The article appeared in a Festschrift devoted to a distinguished Polish linguist Professor Alfred F. Majewicz. It discusses the Christian name Alfred born by the Jubilarian in its various aspects: its Anglo-Saxon origins, etymology and popularity (past and present) in various European countries, with particular emphasis on Poland. It also presents some famous people, literary characters and pop culture heroes bearing this name.

Moriscos peninsulares, moros filipinos y el islam en el extremo oriental del imperio español: estudio y edición de la Segunda carta para la S.C.M.R. acerca de los mahometanos de las Philipinas de Melchor de Ávalos (1585)

Exposición y análisis de los argumentos que utilizó Melchor de Ávalos en la "Segunda carta para la S.C.M.R acerca de los mahometanos de las Philipinas", que dirige a Felipe II en 1585. Se concluye que son argumentos del derecho canónico que ya se utilizaron para justificar la conquista de al-Andalus primero y luego la expulsión de los moriscos. Se publica como apéndice este documento.

Vita della venerabile serva di Dio, Maria Cristina di Savoia, regina delle Due Sicilie cavata da'processi per la di lei beatificazione e canonizzazione.

Mode of access: Internet.

Dell'argenteo imbusto al primo patrono S. Gennaro da re Carlo Secondo di Angiò decretato : con una disquisizione intorno al Libro delle spese della casa dello stesso re, dove s'indagano gli anni ai quali va assegnato se ne classificato le notizie più interessanti, e si fa accurata rassegna dei pesi e delle misure state in uso nel reame di Napoli /

Last leaf blank.

Descripcion del túmulo y relacion de las exequias que hizo la ciudad de Sevilla en la muerte del rey don Felipe segvndo,

"Prologo del editor" signed: Francisco de B. Palomo.

Mélanges biographiques et littéraires,

Mode of access: Internet.

Heinrich Ludewig Manger's, Königl. Preuss. Ober-Hof-Baurath und Garteninspectors, Baugeschichte von Potsdam : besonders unter der Regierung König Friedrichs des Zweiten.

1. Bd. Die Baugeschichte von den ältesten Zeiten bis 1762 -- 2. Bd. Die Baugeschichte vom Jahre 1763 bis zu 1786 -- 3. Bd. Nachrichten von den Baumeistern, Kassenverwaltern, den übrigen Vorfällen und ein Verzeichniss der verwendeten Baukosten. Register über alle drey Bände.

Über die Flugschriften Friedrich's des Grossen aus der Zeit des siebenjährigen Krieges /

Includes some text in French.

Rameses the Great; or, Egypt 3300 years ago.

Mode of access: Internet.

König Philipp, Sohn des Amyntas von Makedonien, und die hellenischen Staaten,

Mode of access: Internet.

Lettres inédites de Mme. la Mise. Du Châtelet [à Maupertuis]

Mode of access: Internet.