Prädiktive Biomarker beim ER+/HER2 - Mammakarzinom - Diskrepanz zwischen S3-Leitlinie, AGO-Empfehlung und St.-Gallen-Expertenmeinung

Auch fur die Behandlung von Brustkrebs bilden Leitlinien und Expertenkonsensus eine unverzichtbare Basis fur eine evidenzbasierte Auswahl der Therapie. In Deutschland sind dies unter anderem die S3-Leitlinie der Deutschen Krebsgesellschaft, die Leitlinien der Arbeitsgemeinschaft Gynakologische Onkologie und der Expertenkonsensus von St. Gallen. Durch sie wurden einheitliche Behandlungsstrategien erreicht und so wesentliche Fortschritte bei der Behandlung des Mammakarzinoms mit ermoglicht. Fur die Entscheidung, ob Patientinnen mit einem luminalen Mammakarzinom der mittleren Risikogruppe mit einer chemo-endokrinen Therapie behandelt werden sollten oder ob eine einfache Hormontherapie ausreich…

Gene Expression Analyses in Early Breast Carcinoma — Quo Vadis?

AbstractIn order to establish whether adjuvant therapy should be administered in patients with breast carcinoma, it is decisive to have as precise as possible an assessment of the risk of recurrence. In this context, gene expression — and thus gene expression signatures as well — have become a focus of attention as prognostic factors. For practical application, it is important to be able to analyze gene expression signatures in formalin-fixed, paraffin-embedded tumor tissue. Careful analytic and clinical validations and a high level of evidence (LoE) are required in order to avoid imprecise risk classification and thus potential overtreatment or undertreatment of the patients. Among the com…

Ligneous Cervicitis in a Woman With Plasminogen Deficiency Associated With an Atypical Form of Microglandular Hyperplasia

A 19-yr-old woman with previously diagnosed clear cell adenocarcinoma was referred to the Charité for further treatment. Biopsies were taken from the cervix, the endometrium, pseudomembranes in the peritoneum, and sentinel lymph nodes. The morphologic picture of pseudomembranes and inflammation together with the provided information about plasminogen deficiency of the patients led to the hypothesis of ligneous cervicitis. The previously taken biopsies of the adenocarcinoma were reevaluated and showed a clear cell lesion. Further immunohistochemical examination with antibodies against p16, Ki67, CEA, and p53 could not prove its malignant character. As a result we diagnosed an atypical form o…

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and one hundred and elev…

Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)

Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distribution of PD-L1 IC–positivity in the pivotal atezolizumab studies (Emens et al., SABCS 2018; JAMA Oncol 2019). Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and…

A multicentre analytical comparison study of inter-reader and inter-assay agreement of four programmed death-ligand 1 immunohistochemistry assays for scoring in triple-negative breast cancer.

AIMS Studies in various cancer types have demonstrated discordance between results from different programmed death-ligand 1 (PD-L1) assays. Here, we compare the reproducibility and analytical concordance of four clinically developed assays for assessing PD-L1-positivity in tumour-infiltrating immune cells in the tumour area (PD-L1-IC-positivity) in triple-negative breast cancer (TNBC). METHODS AND RESULTS Primary TNBC resection specimens (n = 30) were selected based on their PD-L1-IC-positivity per VENTANA SP142 ( 5%: eight cases). Serial histological sections were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3 and DAKO 28-8. PD-L1-IC-positivity and tumour cell expression (…

A randomized, open-label, multicentre, phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy based treatment strategy in patients with hormone receptor positive/HER2-negative metastatic breast cancer in a real world setting.

TPS1115 Background: Although endocrine based therapy is recommended as first-line treatment in metastatic breast cancer (MBC) in patients with an HER2-/HR+ tumour up to 50% of the patients receive chemotherapy. Palbociclib (P) a CDK4/6 inhibitor improves PFS by 42% in endocrine sensitive and resistant HER2-/HR+ MBC when added to an endocrine therapy (ET). Patients included in clinical trials are often criticised not to be representative for real world breast cancer patients. Methods: Patients with first-line HER2-/HR+ MBC who are candidate for mono-chemotherapy will be eligible to be randomised 1:1 to receive either P plus ET per label or mono-chemotherapy per investigator´s choice with or…

Anti-hormonal maintenance treatment with or without the CDK4/6 inhibitor ribociclib after first line chemotherapy in hormone receptor positive/HER2 negative metastatic breast cancer: A phase II trial (AMICA) GBG 97

The EndoPredict Gene-Expression Assay in Clinical Practice - Performance and Impact on Clinical Decisions

The validated EndoPredict assay is a novel tool to predict the risk of metastases of patients with estrogen receptor positive, HER2 negative breast cancer treated with endocrine therapy alone. It has been designed to integrate genomic and clinical information and includes clinico-pathological factors such as tumor size and nodal status. The test is feasible in a decentral setting in molecular pathology laboratories. In this project, we investigated the performance of this test in clinical practice, and performed a retrospective evaluation of its impact on treatment decisions in breast cancer. During one year, EndoPredict assays from 167 patients could be successfully performed. For retrospe…

Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple negative breast cancer (TNBC)

Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distribution of PD-L1 IC–positivity in the pivotal atezolizumab studies (Emens et al., SABCS 2018; JAMA Oncol 2019). Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and…

A Novel Multigene Assay in Clinical Practice - Performance and Impact On Clinical Decisions

Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2–Positive and Triple-Negative Primary Breast Cancers

Purpose Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, …

Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2)

Abstract Background The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed. Patients and methods GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m2, nab-paclitaxel (nP) 330 mg/m2 and cyclophosphamide (C) 2000 mg/m2 (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD…

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer

Geburtshilfe und Frauenheilkunde 78(11), 1056-1088 (2018). doi:10.1055/a-0646-4630

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80&ndash

From High-Throughput Microarray-Based Screening to Clinical Application: The Development of a Second Generation Multigene Test for Breast Cancer Prognosis

Several multigene tests have been developed for breast cancer patients to predict the individual risk of recurrence. Most of the first generation tests rely on proliferation-associated genes and are commonly carried out in central reference laboratories. Here, we describe the development of a second generation multigene assay, the EndoPredict test, a prognostic multigene expression test for estrogen receptor (ER) positive, human epidermal growth factor receptor (HER2) negative (ER+/HER2−) breast cancer patients. The EndoPredict gene signature was initially established in a large high-throughput microarray-based screening study. The key steps for biomarker identification are discussed in det…

Targeted mRNA sequencing of small formalin-fixed and paraffin-embedded breast cancer samples for the quantification of immune and cancer-related genes

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer

62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, DGGG'18, Berlin, Germany, 31 Oct 2018 - 3 Nov 2018; Geburtshilfe und Frauenheilkunde 78(10), 927-948 (2018). doi:10.1055/a-0646-4522 special issue: "62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, DGGG'18, Berlin, 31.10 – 03.11.2018 : Frauenheilkunde im Fokus: wissenschaftlich fundiert und der Qualität verpflichtet"

Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry—Comparison of Three Different GPA Prognostic Scores

Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and l…