Preventing alpelisib-related hyperglycaemia in HR+/HER2-/-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial.

Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/-mutated advanced breast cancer (ABC).

Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.

Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia.

Objectives: Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the and genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing.

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study.

Background: The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer.

Methods: In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%.

Drug cost avoidance analysis of cancer clinical trials in Spain: a study on cost contributors and their impact.

Objective: Analyze the cost contributors and their impact on the drug cost avoidance (DCA) resulting from cancer clinical trials over the period of 2015-2020 in a tertiary-level hospital in Spain (HCUVA).

Methods: We performed a cross-sectional, observational, retrospective study of a total of 53 clinical trials with 363 patients enrolled. We calculated the DCA from the price of the best standard of care (i.

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study.

Background: An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis.

Methods: Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2).

Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance.

Introduction: BRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed.

Material And Methods: an analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2.

Sapanisertib plus Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive/HER2-Negative Advanced Breast Cancer after Progression on Aromatase Inhibitor.

Purpose: This phase II study investigated daily or weekly sapanisertib (a selective dual inhibitor of mTOR complexes 1 and 2) in combination with fulvestrant.

Patients And Methods: Postmenopausal women with estrogen receptor-positive (ER+)/HER2-negative (HER2-) advanced or metastatic breast cancer following progression during/after aromatase inhibitor treatment were randomized to receive fulvestrant 500 mg (28-day treatment cycles), fulvestrant plus sapanisertib 4 mg daily, or fulvestrant plus sapanisertib 30 mg weekly, until progressive disease, unacceptable toxicity, consent withdrawal, or study completion.

Results: Among 141 enrolled patients, baseline characteristics were balanced among treatment arms, including prior cyclin-dependent kinase-4/6 (CDK4/6) inhibitor treatment in 33% to 35% of patients.

Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study.

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR).

Analysis of adolescent oncology cases from 2008 through 2018 in a tertiary-level hospital: an opportunity for improvement.

The purpose of this study was to disclose the variability of pathways currently taken in the treatment of adolescent patients from diagnosis to final follow-up with a view to developing a more homogenous system. A cross-sectional, observational and retrospective study of the cancer diagnosis and assignment to medical care teams in adolescent patients (12-20 years) from January 2008 to December 2018 was conducted. A total of 345 adolescent patients aged between 12 and 20 years, diagnosed with cancer and treated at Hospital Clinico Universitario Virgen de la Arrixaca were included.

Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies.

The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is based on disease progression as a tumor cell-autonomous process, regardless the effects of the host immune response. The natural history of a tumor includes different phases of growth, migration and invasion. During these phases, tumor cells interact with their microenvironment and are influenced by signals from stromal, endothelial, inflammatory and immune cells.

Type 2 Diabetes Alters Intracellular Ca Handling in Native Endothelium of Excised Rat Aorta.

An increase in intracellular Ca concentration ([Ca]) plays a key role in controlling endothelial functions; however, it is still unclear whether endothelial Ca handling is altered by type 2 diabetes mellitus, which results in severe endothelial dysfunction. Herein, we analyzed for the first time the Ca response to the physiological autacoid ATP in native aortic endothelium of obese Zucker diabetic fatty (OZDF) rats and their lean controls, which are termed LZDF rats. By loading the endothelial monolayer with the Ca-sensitive fluorophore, Fura-2/AM, we found that the endothelial Ca response to 20 µM and 300 µM ATP exhibited a higher plateau, a larger area under the curve and prolonged duration in OZDF rats.

New insights into the performance of multigene panel testing: Two novel nonsense variants in BRIP1 and TP53 in a young woman with breast cancer.

Li-Fraumeni syndrome is an autosomal-dominant disorder caused by germline mutations in the tumour suppressor gene TP53. Here we report the case of a family whose index case was a woman diagnosed with bilateral breast cancer at the age of 18 and who had a non-informative result after BRCA1 and BRCA2 testing. After extending the study through multigene panel testing, two clinically relevant variants in the TP53 and BRIP1 genes, respectively, were found.

SIRT1 and Estrogen Signaling Cooperation for Breast Cancer Onset and Progression.

Breast cancer remains a significant female mortality cause. It constitutes a multifactorial disease for which research on environmental factors offers little help in predicting onset or progression. The pursuit for its foundations by analyzing hormonal changes as a motive for disease development, indicates that increased exposure to estrogens associates with increased risk.

Mutational analysis of RAD51C and RAD51D genes in hereditary breast and ovarian cancer families from Murcia (southeastern Spain).

RAD51C and RAD51D have been defined as susceptibility genes for hereditary breast and ovarian cancer syndrome in several studies. In the present study, a mutation analysis of these genes was performed on non BRCA1/2 families. RAD51C and RAD51D genes were analyzed in 141 and 77 families, respectively.

Sirt1 interaction with active Smad2 modulates transforming growth factor-β regulated transcription.

Background: The simplicity of Transforming Growth Factor ß (TGFβ) signaling pathway, linear and non-amplified, hardly sustains its variety of responses. This is often justified by the complex regulation showed by Smad proteins, TGFβ signaling intracellular transducers, object of post-translational modifications that modulate TGFβ-dependent transcription. Protein acetylation is emerging as a compelling mechanism affecting the activities of significant transcription factors, including p53, FOXO or NF-kB.

Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical-pathological features in BRCA carriers and non-carriers.

This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained.

Potential drug-drug interactions in oncological adult inpatients at a Spanish hospital: epidemiology and risk factors.

Background: Oncological patients are at high risk for drug-drug interactions (DDIs), which may contribute to therapeutic failure or lead to serious adverse events.

Objective: To determine the prevalence of potential DDIs in medication lists, to describe the most frequent DDIs and to investigate the possible risk factors associated with them. A prospective cohort study was performed at the Oncology Department of a tertiary hospital over a 12-week period.

Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry.

Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein.

Intertrigo-like eruption caused by pegylated liposomal doxorubicin (PLD).

Pegylated liposomal doxorubicin (PLD) is a drug whose use is increasingly common. It has been associated with a lower rate of haematologic and cardiac side effects than its nonencapsulated form. However, mucocutaneous toxicity is quite frequent and can be severe.

[Immunohistochemical characterisation of breast cancer: towards a new clasification?].

Background: The aim of this paper is to determine the possible association between five different profiles of immunohistochemical expression related to clinical, histopathological and immunohistochemical known prognostic value variables for breast cancer.

Material And Method: A total of 194 breast carcinoma tumour samples were studied. In this study five groups or immunohistochemical profiles were defined, based on expression of hormone receptors (oestrogen or progesterone) and/or Her2/neu (luminal-type A, luminal-type B, mixed profile, Her2/neu profile and triple-negative-type profile) and we studied whether there are differences between them with regard to clinical, histopathological and immunohistochemical variables that have a known prognostic significance.

[Primary non-lymphoid thymic neoplasms. A study of 58 cases].

Background And Objective: Primary non-lymphoid thymus tumors (PNLTT) are an uncommon though quite varied pathology. Our objective was to identify the clinical, therapeutic and histologic variables with a prognostic value in these neoplasms.

Patients And Method: We studied 58 PNLTT cases, corresponding to 52 epithelial neoplams (PTEN), 4 thymolipomas (7%) and 2 neuroendocrine tumors (3%).