Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

RAD51 testing in patients with early HER2-negative breast cancer and homologous recombination deficiency: post-hoc analysis of the GeparOla trial.

Purpose: The randomized GeparOla trial reported comparable pathological complete response (pCR) rates with neoadjuvant containing olaparib vs. carboplatin treatment. Here, we evaluate the association between functional homologous repair deficiency (HRD) by RAD51 foci and pCR, and the potential of improving patient selection by combining RAD51 and stromal tumor infiltrating lymphocytes (sTILs).

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).

Endoscopic submucosal dissection of colorectal pedunculated polyps.

For pedunculated colon polyps, en bloc resection with inclusion of the polyp stalk is necessary to yield an accurate histologic staging. This can be challenging in cases of a large polyp and/or broad stalk using conventional snare resection. We evaluated the feasibility of endoscopic submucosal dissection (ESD) for large pedunculated polyps with broad stalks.

Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

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).

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.

TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis.

Antibody-drug conjugates (ADCs) directed to trophoblast cell surface antigen 2 (TROP2) have gained approval as a therapeutic option for advanced triple-negative breast cancer, and TROP2 expression has been linked to unfavourable outcomes in various malignancies. In colorectal carcinoma (CRC), there is still a lack of comprehensive studies on its expression frequency and its prognostic implications in relation to the main clinicopathological parameters. We examined the expression of TROP2 in a large cohort of 1,052 CRC cases and correlated our findings with histopathological and molecular parameters, tumour stage, and patient outcomes.

GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer.

GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment.

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.

An Analysis of PIK3CA Hotspot Mutations and Response to Neoadjuvant Therapy in Patients with Breast Cancer from Four Prospective Clinical Trials.

Purpose: The PI3K signaling pathway is frequently dysregulated in breast cancer, and mutations in PIK3CA are relevant for therapy resistance in HER2-positive (HER2pos) breast cancer. Mutations in exons 9 or 20 may have different impacts on response to neoadjuvant chemotherapy-based treatment regimens.

Experimental Design: We investigated PIK3CA mutations in 1,691 patients with early breast cancer who were randomized into four neoadjuvant multicenter trials: GeparQuattro (NCT00288002), GeparQuinto (NCT00567554), GeparSixto (NCT01426880), and GeparSepto (NCT01583426).

DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer.

Objective: Highly malignant pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant immunosuppressive and fibrotic tumour microenvironment (TME). Future therapeutic attempts will therefore demand the targeting of tumours and stromal compartments in order to be effective. Here we investigate whether dual specificity and tyrosine phosphorylation-regulated kinase 1B (DYRK1B) fulfil these criteria and represent a promising anticancer target in PDAC.

Quality-Assured Analysis of PIK3CA Mutations in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Tissue.

In precision oncology, reliable testing of predictive molecular biomarkers is a prerequisite for optimal patient treatment. Interlaboratory comparisons are a crucial tool to verify diagnostic performance and reproducibility of one's approach. Herein is described the design and results of the first recurrent, internationally performed PIK3CA (phosphatidylinositol-4,5-bisphosphate 3 kinase catalytic subunit α) breast cancer tissue external quality assessment (EQA), organized by German Quality in Pathology GmbH and started in 2021.

NGS-Guided Precision Oncology in Breast Cancer and Gynecological Tumors-A Retrospective Molecular Tumor Board Analysis.

Precision oncology treatments are being applied more commonly in breast and gynecological oncology through the implementation of Molecular Tumor Boards (MTBs), but real-world clinical outcome data remain limited. A retrospective analysis was conducted in patients with breast cancer (BC) and gynecological malignancies referred to our center's MTB from 2018 to 2023. The analysis covered patient characteristics, next-generation sequencing (NGS) results, MTB recommendations, therapy received, and clinical outcomes.

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.

Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy.

Background: Neoadjuvant chemotherapy (NACT) is routinely used for patients with triple-negative breast cancer (TNBC). Upfront breast-conserving therapy (BCT) consisting of breast-conserving surgery (BCS) and adjuvant radiotherapy (RT) has been shown to be associated with improved outcome in patients with early TNBC as compared to mastectomy.

Methods: We identified 2632 patients with early TNBC from the German Breast Group meta-database.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

Purpose: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations.

Methods: Statements and voting results from the 18th St.

Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.

Background: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group.

AHRR and SFRP2 in primary versus recurrent high-grade serous ovarian carcinoma and their prognostic implication.

Background: The aim of this study was to analyse transcriptomic differences between primary and recurrent high-grade serous ovarian carcinoma (HGSOC) to identify prognostic biomarkers.

Methods: We analysed 19 paired primary and recurrent HGSOC samples using targeted RNA sequencing. We selected the best candidates using in silico survival and pathway analysis and validated the biomarkers using immunohistochemistry on a cohort of 44 paired samples, an additional cohort of 504 primary HGSOCs and explored their function.