Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX®, MammaPrint®, Prosigna®, or EndoPredict®) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors. METHODS: Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections. RESULTS: Histological analysis showed decreased sTILs, CD20+ cells, and CD8+/CD4+ ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4+ and Foxp3+ T cells, while it was inversely correlated with CD8+/CD4+ and CD8+/Foxp3+ ratios. CONCLUSION: sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumors.

Effect of reflux and esophagitis on esophageal volume and acid clearance in piglets.

BACKGROUND/AIMS: The study investigates esophageal motor function and esophageal clearance immediately after surgical induction of reflux in piglets and 8 weeks later after peptic esophagitis has developed. METHODS: Twenty-four sedated, nonintubated piglets were divided into three groups: sham (laparotomy only), reflux (distal esophageal myotomy), and reflux + esophagitis (8 weeks after myotomy). All animals underwent stationary manometry of the esophagus with a four-lumen perfused assembly after injection of 1-, 2-, and 3-mL boluses of saline and acid into the proximal esophagus. Simultaneous pH monitoring allowed assessment of acid clearance. Wave features and clearance times after saline and acid were compared among groups. RESULTS: There were minor changes in peristaltic activity of the esophagus after saline boluses in animals with reflux. Acid clearance time was prolonged, especially the time to re-establish resting esophageal pH, in animals with esophagitis. These changes, which were volume-dependent, were related to the loss of peristaltic organization of the esophageal waves. The esophageal wave frequency, amplitude, and duration were only slightly changed by the induction of reflux and by esophagitis. CONCLUSIONS: The esophagus affected by acid reflux, with or without esophagitis, was capable of near-normal motor responses after boluses of saline. Reflux impaired the peristaltic response to acid, and the effect was more pronounced when reflux and esophagitis were both present. The acid clearance time was also strikingly prolonged in the presence of reflux and esophagitis. The results suggest that long episodes of reflux seen on pH tracings from individuals with esophagitis might be secondary both to acid-related motor dysfunction and large volumes of refluxate.