Germline BRCA1/2 mutations and severe haematological toxicities in patients with breast cancer treated with neoadjuvant chemotherapy.

Background: BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities.

Methods: Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed.

Reconstructing tumor history in breast cancer: signatures of mutational processes and response to neoadjuvant chemotherapy.

Background: Different endogenous and exogenous mutational processes act over the evolutionary history of a malignant tumor, driven by abnormal DNA editing, mutagens or age-related DNA alterations, among others, to generate the specific mutational landscape of each individual tumor. The signatures of these mutational processes can be identified in large genomic datasets. We investigated the hypothesis that genomic patterns of mutational signatures are associated with the clinical behavior of breast cancer, in particular chemotherapy response and survival, with a particular focus on therapy-resistant disease.

Correction: Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine.

[This corrects the article DOI: 10.1055/a-1286-2917.].

Prospective Evaluation of All-lesion Versus Single-lesion Radiotherapy in Combination With PD-1/PD-L1 Immune Checkpoint Inhibitors.

Background: Local ablative treatments improve survival in patients with oligometastatic disease in addition to chemotherapy. The application of immune checkpoint inhibitors prolonged patients' survival in different tumor entities. This raises the question if patients still benefit from intensified local treatments in combination with a more efficient systemic treatment with immune checkpoint inhibitors.

Understanding PD-L1 Testing in Breast Cancer: A Practical Approach.

Background: Immune checkpoint inhibitors (ICI) have changed therapy strategies for cancer patients tremendously. Some approved ICI acquire testing of PD-L1 expression on tumor and/or immune cells. However, since PD-L1 testing is a comprehensive issue with various assays, antibody clones, scoring methods, and cut-offs, we aimed to summarize the recommendations and technical and histopathological issues of diagnostic PD-L1 assessment with an emphasis on invasive breast cancer (IBC).

Gynecologists' attitudes toward and use of complementary and integrative medicine approaches: results of a national survey in Germany.

Purpose: Despite patients' widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals' current implementation of it in clinical routine. A national survey was conducted to assess gynecologists' attitudes to and implementation of complementary and integrative treatment approaches.

Methods: The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019.

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients.

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine.

Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment.

HLA-J, a Non-Pseudogene as a New Prognostic Marker for Therapy Response and Survival in Breast Cancer.

The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a "pseudogene" by in silico sequence interpretation.

Update Breast Cancer 2020 Part 4 - Advanced Breast Cancer.

Substances with good effectiveness that intervene in specific signalling pathways have been used increasingly in recent years in the treatment of patients with advanced breast cancer, and new therapies and approaches have now been added, which actually relate to quite specific changes, such as the treatment of patients with HR+/HER2 tumours with a mutation. The treatment of patients with a or mutation has also been improved by the introduction of PARP inhibitors. Attempts are now being made increasingly to extend treatment indications based on molecular patterns, to identify other patients who could benefit from a treatment and to integrate the newly established treatment methods in existing therapy sequences.

Update Breast Cancer 2020 Part 3 - Early Breast Cancer.

The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation.

Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor?

The role of tumour-infiltrating inflammatory cells (TIICs) in the disease progression of hormone-receptor-positive breast cancer (HR+ BC) is largely unclear since it is generally regarded as the least immunogenic BC subtype. This study investigated the prognostic significance of CD1a+ dendritic cells, CD20+ B cells, CD45RO+ memory T cells and CD4+ T-helper cells in HR+ BC. One hundred and forty-six patients were treated for early stage, distant-metastases-free HR+ BC in an accelerated partial breast irradiation (APBI) phase II trial.

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting.

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study.

Purpose: In the MONALEESA-3 Phase III trial of patients with hormone receptor-positive human epidermal growth factor receptor-negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL).

Methods: Patients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant.

Prospective evaluation of the prognostic value of immune-related adverse events in patients with non-melanoma solid tumour treated with PD-1/PD-L1 inhibitors alone and in combination with radiotherapy.

Background: Prospective data about the prognostic value of immune-related adverse events (irAEs) in non-melanoma solid tumours are rare. The prognostic value of irAEs in patients treated with combined radiotherapy and immunotherapy is currently unknown.

Patients And Methods: The prospective non-interventional ST-ICI trial investigates treatment response of tumour patients to anti-programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors alone and in combination with radiotherapy and possible predictive markers.

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8.

Background: To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.

Methods: Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab.

Gene Expression Signatures of BRCAness and Tumor Inflammation Define Subgroups of Early-Stage Hormone Receptor-Positive Breast Cancer Patients.

Purpose: Patients with estrogen receptor- and/or progesterone receptor-positive, early breast cancer benefit from hormonal treatment, yet high global death burdens due to high prevalence and long-term recurrence risk call for biomarkers to guide additional treatment approaches.

Experimental Design: From a prospective, observational study of postmenopausal early breast cancer patients treated with tamoxifen or aromatase inhibitors, gene expression analyses of 612 tumors was performed using the NanoString Breast Cancer 360 panel to interrogate 23 breast cancer pathways. Candidate signatures associated with disease subtype and event-free survival (EFS) were obtained by cluster analysis, Cox modeling, and conditional inference trees, and were independently tested in 613 patients from BreastMark.

Genetic variations in estrogen and progesterone pathway genes in preeclampsia patients and controls in Bavaria.

Purpose: Hypertensive pregnancy disorders and preeclampsia are major causes of maternal and fetal morbidity and mortality worldwide. Many different organs are involved in the diseases' clinical phenotype. The underlying mechanism is still unknown, with a possible genetic component.

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

: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. : The aim of this analysis was to characterize patients with asymptomatic BM ( = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. : Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.

Assessment of the additional clinical potential of X-ray dark-field imaging for breast cancer in a preclinical setup.

Background: Mammography can identify calcifications up to 50-100 μm in size as a surrogate parameter for breast cancer or ductal carcinoma (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications.

PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer.

PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome.

Histology of Luminal Breast Cancer.

Background: Invasive breast cancer (IBC) can be categorized into prognostic and predictive molecular subtypes (including luminal breast cancer) using gene expression profiling. Luminal IBC comprises a variety of histological subtypes with varying clinical and pathological features.

Summary: IBC of no special subtype is the most common histological subtype in general and likewise within luminal IBC.