Decisional conflict and knowledge in women with BRCA1/2 pathogenic variants: An exploratory age group analysis of a randomised controlled decision aid trial.

Female BRCA1/2 pathogenic variant (PV) carriers face substantial risks for breast and ovarian cancer. Evidence-based decision aids (DAs) can facilitate these women in their decision-making process on an individually suitable preventive strategy. However, there is a gap in previous literature exploring whether DA effectiveness varies according to women's age.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer.

Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024.

Results And Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

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.

Decision Coaching for Healthy Women With BRCA1/2 Pathogenic Variants—Findings of the Randomized Controlled EDCP-BRCA Trial.

Background: Women with pathogenic variants (PV) of the genes BRCA1/2 have a choice of preventive options. To help these women decide for themselves, we developed and implemented a decision coaching (DC) program and evaluated it for congruence between the participants' desired and actual roles in decision-making.

Methods: Healthy BRCA1/2 PV carriers (25-60 years of age) were recruited at six centers in Germany.

Predictors of knowledge and knowledge gain after decision aid use among women with BRCA1/2 pathogenic variants.

Objective: To identify factors contributing to baseline knowledge in women with BRCA1/2 pathogenic variants (PVs) and knowledge gain after decision aid (DA) use.

Methods: Women with PVs in BRCA1 or BRCA2 genes were randomly assigned to an intervention group (IG) receiving DAs or a control group (CG). Of the total sample, 417 completed the baseline survey and were included in this analysis.

Implementing mainstream genetic counseling within the area-wide network of the German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC): Satisfaction of primary care providers with the provided state-of-the-art training by the Cologne Center.

The German Cancer Society (Deutsche Krebsgesellschaft DKG) has published a position paper to address the challenges of cancer patient care in the era of genomic medicine. The German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC) has implemented this recommendation in its care concept for families at risk. Core elements are the outcome-oriented evaluation of structured and standardized clinical measures and reporting recommendations derived therefrom to primary care providers and patients.

Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in g Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer.

Purpose: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline , high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment.

Methods: Data were collected before random assignment, and at 6, 12, 18, and 24 months.

Phenotype analysis of families with TP53 germline variants at the Center for Familial Breast and Ovarian Cancer, Cologne.

Purpose: Tumor protein p53 (TP53) pathogenic variant (PV) carriers are identified during genetic testing for hereditary causes of cancer. PVs in TP53 are associated with the Li-Fraumeni syndrome (LFS), and thus, surveillance and preventive measures are important for TP53 PV carriers. However, the penetrance of TP53 PVs can be low if the Chompret criteria are not fulfilled.

Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction.

Background: Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines.

Methods: For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21-74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk.

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2023.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC).

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2023.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer.

Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023.

Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Effectiveness of evidence-based decision aids for women with pathogenic BRCA1 or BRCA2 variants in the german health care context: results from a randomized controlled trial.

Background: Women with pathogenic BRCA1 or BRCA2 variants are at high risk for breast and ovarian cancer. Preventive options include risk-reducing breast and ovarian surgeries and intensified breast surveillance. However, individual decision-making is often associated with decisional conflicts.

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.

Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation.

Background: Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC.

Methods: The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study.

Pathogenic germline variants in SMARCA4 and further cancer predisposition genes in early onset ovarian cancer.

To assess the role of germline pathogenic variants (PVs) in and further established ovarian cancer (OC) predisposition genes in early onset OC, we investigated a clinical cohort of 206 unrelated OC index patients with an age at diagnosis of OC ≤40 years using an extended panel of 24 (candidate) cancer predisposition genes. PVs in established OC predisposition genes were most frequent in patients with high grade serous OC (21/62, 33.9%), comparatively rare in patients with epithelial OC other than high grade serous (5/74, 6.

Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer.

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis.

Assessing Psychological Morbidity in Cancer-Unaffected Pathogenic Variant Carriers: A Systematic Review.

Female pathogenic variant carriers have an increased lifetime risk for breast and ovarian cancer. Cancer-unaffected women who are newly diagnosed with this pathogenic variant may experience psychological distress because of imminent health threat. No comprehensible review on psychological morbidity in cancer-unaffected pathogenic variant carriers is currently available.

Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients.

Data on deleterious variants in genes other than remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded.

Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy.

This retrospective pooled analysis aims to identify factors predicting relapse despite a pathologic complete response (pCR) in patients with breast cancer (BC). 2066 patients with a pCR from five neoadjuvant GBG/AGO-B trials fulfill the inclusion criteria of this analysis. Primary endpoint is disease-free survival (DFS); secondary endpoints is distant DFS (DDFS) and overall survival (OS).

The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy.

Background: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient's pathologic complete response (pCR) rate.

Psychological distress and decision-making factors for prophylactic bilateral mastectomy in cancer-unaffected BRCA1/2 pathogenic variant carriers.

Objective: Women carrying a BRCA1/2 pathogenic variant have an increased risk for breast cancer and may opt for risk-reducing bilateral mastectomy. In this study, we examine which demographic, psychosocial, and personality factors are associated with their decision to undergo risk-reducing bilateral mastectomy.

Methods: Cancer-unaffected women with a pathogenic variant in BRCA1 or BRCA2 were recruited before receiving their genetic test result and completed follow-up including decision to undergo mastectomy over 6-8 months after genetic test result disclosure.

Coping Self-Efficacy and Its Relationship with Psychological Morbidity after Genetic Test Result Disclosure: Results from Cancer-Unaffected Mutation Carriers.

Women who are found to carry a pathogenic variant experience psychological distress due to an increased risk of breast and ovarian cancer. They may decide between different preventive options. In this secondary analysis of data collected alongside a larger randomized controlled trial, we are looking at 130 newly found pathogenic variant carriers and how their coping self-efficacy immediately after genetic test result disclosure is related to their psychological burden and status of preventive decision making.

Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer.

The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice test on all the patients with an indication for tumor HRD testing.