Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial.

Background: Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear.

Methods: In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome).

On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.

Background: Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies.

Methods: On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto).

BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.

Recent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer (PC) progression. However, driver genes that direct EV function, the EV-recipient cells, and their cellular response to EV uptake remain to be identified. Therefore, we studied the role of Bcl-2-associated-anthanogene 6 (BAG6), a regulator of EV biogenesis for cancer progression.

Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE).

Background: The GENEVIEVE study, comparing neoadjuvant cabazitaxel versus paclitaxel in triple-negative breast cancer (TNBC) and luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC), previously reported significant differences in pathological complete response (pCR) rates. Effects on long-term outcome are unknown.

Patients And Methods: GENEVIEVE randomized patients with cT2-3, any cN or cT1, cN+/pN+, centrally confirmed TNBC or luminal B/HER2-negative BC (latter defined as estrogen/progesterone receptor-positive and >14% Ki-67-stained cells) to receive either cabazitaxel 25 mg/m q3w for four cycles or paclitaxel 80 mg/m weekly for 12 weeks.

Plasmapheresis as therapeutic option in a 16-year-old with EVALI: A case report.

Since 2019 when a cluster of cases with acute respiratory distress syndrome (ARDS) associated with e-cigarettes in the United States was reported, there have been increasing numbers of reports. Electronic-cigarette or Vaping Use-associated Lung Injury (EVALI) represents a recent entity of respiratory clinical syndromes, primarily in young adults. We report a previously healthy 16-year-old boy who developed severe ARDS following a brief nonspecific prodromal phase after excessive consumption of e-cigarettes.

RANK Expression as an Independent Predictor for Response to Neoadjuvant Chemotherapy in Luminal-Like Breast Cancer: A Translational Insight from the GeparX Trial.

Purpose: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel-based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m² weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published.

An integrated cellular and molecular model of gastric neuroendocrine cancer evolution highlights therapeutic targets.

Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We identify global and subtype-specific alterations and expose hitherto unappreciated gains of MYC family members in a large part of cases.

ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer.

Characterization of Hormone Receptor and HER2 Status in Breast Cancer Using Mass Spectrometry Imaging.

Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers.

Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer.

Purpose: In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT.

Experimental Design: Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes, classified by Absolute Intrinsic Molecular Subtyping.

Selecting patients with HER2-low breast cancer: Getting out of the tangle.

The promising effect of antibody-drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable.

pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas-proposal for a new pT3a/pT3b subclassification.

Background: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision.

Methods: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich).

Response-based molecular subtyping-emergence of the third generation of breast cancer subtypes.

The therapeutic landscape of breast cancer is becoming increasingly complex. In this issue of Cancer Cell, Wolf et al. present a breast cancer classification scheme that allows for better prediction of treatment response and can be continuously adapted to guide prioritization of new treatments.

Multiparametric Phenotyping of Circulating Tumor Cells for Analysis of Therapeutic Targets, Oncogenic Signaling Pathways and DNA Repair Markers.

Detection of circulating tumor cells (CTCs) has been established as an independent prognostic marker in solid cancer. Multiparametric phenotyping of CTCs could expand the area of application for this liquid biomarker. We evaluated the Amnis brand ImageStreamX MkII (ISX) (Luminex, Austin, TX, USA) imaging flow cytometer for its suitability for protein expression analysis and monitoring of treatment effects in CTCs.

Polycomb Protein BMI-1 as a Potential Therapeutic Target in Mucinous Ovarian Cancer.

Background/aim: Mucinous ovarian carcinoma (mOC) is a rare subtype with distinct clinical characteristics and biological behavior that differentiate them from other epithelial ovarian cancers. This study aimed to evaluate BMI-1 expression as a potential target for therapeutic approaches in advanced stage mOC.

Materials And Methods: We performed gene set, as well as transcription factor enrichment analysis and immunohistochemistry assessing of the BMI-1 protein levels in tissue specimens of eighteen mucinous ovarian cancer patients.

Comparison of risk assessment in 1652 early ER positive, HER2 negative breast cancer in a real-world data set: classical pathological parameters vs. 12-gene molecular assay (EndoPredict).

Background: Risk assessment on the molecular level is important in predictive pathology to determine the risk of metastatic disease for ERpos, HER2neg breast cancer. The gene expression test EndoPredict (EP) was trained and validated for prediction of a 10-year risk of distant recurrence to support therapy decisions regarding endocrine therapy alone or in combination with chemotherapy. The EP test provides the 12-gene Molecular Score (MS) and the EPclin-Score (EPclin), which combines the molecular score with tumor size and nodal status.

Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness.

In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group.

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs.