Does an Autoimmune Disorder Following Ovarian Cancer Diagnosis Affect Prognosis?

We investigated whether developing an autoimmune disorder (AID) following a high-grade epithelial ovarian cancer diagnosis improves overall survival. This retrospective study included data from women treated for high-grade serous, endometrioid, or transitional cell ovarian, fallopian tube, or peritoneal cancer FIGO stage III or IV at a Swiss cantonal gynecological cancer center (2008-2023). We used Kaplan-Meier estimates and the Cox proportional hazards model using time-varying covariates for the survival function estimation. In all, 9 of 128 patients developed an AID following a cancer diagnosis. The median time from cancer diagnosis to AID was 2 years (IQR 2-5). These women survived for a median of 3031 days (IQR 1765-3963) versus 972 days (IQR 568-1819) for those who did not develop an AID (p = 0.001). The median overall survival of nine women with a pre-existing AID was 1093 days (IQR 716-1705), similar to those who never had an AID. The multivariate analyses showed older age (p = 0.003, HR 1.04, 95% CI 1.013-1.064) was associated with a poorer prognosis, and developing an AID after a cancer diagnosis was associated with longer survival (p = 0.033, HR 0.113, 95% CI 0.015-0.837). Clinical manifestations of autoimmune disorders following ovarian cancer diagnoses were associated with better overall survival (8 versus 2.7 years), indicating an overactive immune response may improve cancer control.

[Diagnosis and treatment of venous thrombosis]. / Management der Venenthrombose.

INTRODUCTION: The subject of this guideline from the Institute of Family Medicine at the University of Zurich (IHAMZ) is the management of venous thrombosis. The review summarizes the current evidence and recommendations from international guidelines (1-6). The IHAMZ-guidelines focus on primary care, they also provide guidance on the coordination of general and specialist medical care as well as on the transition between outpatient and hospital care taking into account the special features of the Swiss healthcare system. The guideline is devided in two parts. Part 1 discusses the diagnosis and treatment of deep vein thrombosis (DVT). A validated algorithm is recommended for the diagnostic process, which begins with the assessment of the clinical probability. With the inclusion of the D-dimer test, the need for subsequent imaging diagnostics can be reduced. The differences between the evaluation of an initial and recurrent DVT are shown and the indications and scope of evidence-based environmental diagnostics (thrombophilia and tumor search) are presented. All patients with DVT should receive anticoagulation (AC) for 3-6 months, as there is a high risk of recurrence with AC 3 months. The duration of the subsequent secondary prophylaxis depends on the presumed risk of recurrence on the one hand and the risk of bleeding on the other. Part 2 is dedicated to special thrombosis situations such as shoulder-arm vein thrombosis (SAVT), cancer-associated thrombosis (CAT) and superficial vein thrombosis (SVT). The article on hormone- and pregnancy-associated DVT, developed together with the Department of Gynecology at the University Hospital of Zurich, discusses the importance of hormonal contraception and menopausal hormone replacement therapy (HRT) as a thrombogenic risk factor as well as special features in the diagnosis and treatment of thrombosis in pregnancy.

Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Update Breast Cancer 2024 Part 1 - Expert Opinion on Advanced Breast Cancer.

Clinical evidence is interpreted based on clinical studies and personal experience which can lead to different interpretations of data. This makes the opinions issued by panels of experts such as the Advanced Breast Cancer Panel which convened in November 2023 for the seventh time (ABC7) particularly important. At the conference, current issues around advanced breast cancer were evaluated by an international team of experts. In 2023 the data on CDK4/6 inhibitors was so extensive that the answers to questions about the sequencing of therapy and the potential use of chemotherapy as an alternative therapy were relatively clear. Moreover, data on antibody drug conjugates which provides a good overview of their uses is available for all molecular subtypes. Some therapeutic settings, including patients with brain metastases or leptomeningeal disease, older patients, locally advanced breast cancer and visceral crises, continue to be particularly important and were discussed in structured sessions. The scientific context of some of the topics discussed at ABC7 is presented and assessed here.

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.

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.

Systematic, noninvasive endometriosis diagnosis in transvaginal sonography by the Swiss Society of Ultrasound in Medicine.

We present a new systematic, comprehensive, checklist-based sonographic assessment of endometriosis in the female true pelvis. Emphasis is placed on practical skills teaching. The newly introduced White Sliding Line (WSL) is the core structure. The WSL separates five compartments (anterior, central, posterior, and lateral right and left) containing dedicated endometriosis signs of mobility and morphology to be checked. This approach relies on the 2016 IDEA Consensus and further developments. It directly connects to the 2021 #ENZIAN Classification Standard. In practice, evaluation follows the proposed checklist in all compartments, judging first sliding mobility between organs and structures in a highly dynamic investigation. A rigorous search for deep endometriosis (DE) is then performed. We treat adhesions due to their great clinical importance and possible, reliable diagnosis by TVS as the fifth endometriosis unit, next to endometrioma, DE, adenomyosis, and superficial endometriosis. Including superficial (peritoneal) endometriosis is a future goal.

MRI of pelvic endometriosis: evaluation of the mr#Enzian classification and the importance of adenomyosis subtypes.

PURPOSE: This study aimed to investigate the utility of the #Enzian classification in magnetic resonance imaging (MRI) for endometriosis assessment, focusing on inter-reader agreement, diagnostic accuracy, and the correlation of adenomyosis with deep endometriosis (DE). METHODS: This IRB- approved retrospective single-center study included 412 women who underwent MRI evaluation for endometriosis between February 2017 and June 2022. Two experienced radiologists independently analyzed MRI images using the #Enzian classification and assessed the type of adenomyosis, if any. The surgical #Enzian classification served as the gold standard for evaluating preoperative MRI results of 45 patients. Statistical analysis was performed to assess inter-reader agreement and diagnostic accuracy. RESULTS: Inter-reader agreement was substantial to excellent (Cohen's kappa 0.75-0.96) for most compartments except peritoneal involvement (0.39). The preoperative MRI showed mostly substantial to excellent accuracy (0.84-0.98), sensitivity (0.62-1.00), specificity (0.87-1.00), positive (0.58-1.00) and negative predictive values (0.86-1.00) for most compartments, except for peritoneal lesions (0.36, 0.17, 1.00, 1.00, 0.26 respectively). A trend with a higher prevalence of concordant DE in women with MR features of external adenomyosis compared to those with internal adenomyosis was visible (p = 0.067). CONCLUSIONS: The mr#Enzian showed mostly high inter-reader agreement and good diagnostic accuracy for various endometriosis compartments. MRI's role is particularly significant in the context of the current paradigm shift towards medical endometriosis treatment. The inclusion of information about the type of adenomyosis in the mr#Enzian classification could enhance diagnostic accuracy and inform treatment planning.

Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119.

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58-0.80) for CPS, 0.55 (95% CI = 0.46-0.64) for TPS, and 0.67 (95% CI = 0.56-0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report about a Male Patient with Pectoral Implants.

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is still a rare extralymphatic lymphoma. As of March 1, 2023, approximately 1,355 cases of BIA-ALCL have been reported worldwide. However, no such case has yet been described with pectoral implants in male patients. Most patients with BIA-ALCL present with nonspecific implant-associated symptoms such as late-onset seroma, swollen breasts, and deformation of implants. Case Presentation: Here, we describe BIA-ALCL in a 76-year-old male patient who presented with a late-onset seroma in order to raise awareness for BIA-ALCL also in men after esthetic chest surgery with silicone pectoral implants. The patient had undergone augmentation of the pectoralis muscle with implants for esthetic reasons 9 years before. First cytological specimens showed no malignancy. A repeated cytological assessment after 6 weeks from recurring seroma showed characteristic CD30+ T-cell clones. Surgery with complete bilateral capsulectomy and implant removal was performed. Due to the early-stage ALCL being limited only to the capsule and no evidence of systemic disease, adjuvant systemic treatment was not considered necessary. Conclusion: Any persisting late-onset seroma also in male patients with pectoral implants should raise suspicion of ALCL as differential diagnosis and should be assessed with cytological examination.

ERBB2-amplified lobular breast carcinoma exhibits concomitant CDK12 co-amplification associated with poor prognostic features.

Most invasive lobular breast carcinomas (ILBCs) are luminal-type carcinomas with an HER2-negative phenotype (ERBB2 or HER2 un-amplified) and CDH1 mutations. Rare variants include ERBB2-amplified subtypes associated with an unfavorable prognosis and less response to anti-HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2-amplified ILBC and compared these characteristics with ERBB2-unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin-embedded formalin-fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast-specific markers was tested by immunohistochemistry (IHC). Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2-amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2-unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2-positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2-amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC.

Intrathecal Therapy Options for Meningeal Carcinomatosis.

Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median survival of these patients is between 3.5 and 4.5 months. Current treatment approaches are based on radiotherapy, systemic and intrathecal therapy. Methotrexate, liposomal cytarabine and trastuzumab are the most common substances used for intrathecal therapy. The aim of this review was to provide an overview of these intrathecal therapy options for meningeal carcinomatosis. A systematic search of the literature was carried out in PubMed using the following search terms: "meningeal metastases", "meningeal carcinomatosis", "leptomeningeal metastasis", "leptomeningeal carcinomatosis", "leptomeningeal disease", "breast cancer", "MTX", "methotrexate", "DepoCyte", "liposomal cytarabine", "trastuzumab" and "anti-HER2". This search resulted in 75 potentially relevant studies, 11 of which were included in this review after meeting the previously determined inclusion and exclusion criteria. The studies differ considerably with regards to study design, cohort size, and dosages of administered drugs. In principle, intrathecal therapy has a tolerable side-effects profile and offers promising results in terms of the median overall survival following treatment with trastuzumab for HER2-positive primary tumors. The focus when treating meningeal carcinomatosis must be on providing a multimodal individual therapeutic approach. However, comprehensive studies which compare the efficacy and side effects of individual pharmaceuticals are lacking. Because of the poor prognosis associated with meningeal carcinomatosis, an approach which treats only the symptoms (best supportive care) should always be considered and discussed with affected patients.

Update Breast Cancer 2023 Part 1 - Early Stage Breast Cancer.

With abemaciclib (monarchE study) and olaparib (OlympiA study) gaining approval in the adjuvant treatment setting, a significant change in the standard of care for patients with early stage breast cancer has been established for some time now. Accordingly, some diverse developments are slowly being transferred from the metastatic to the adjuvant treatment setting. Recently, there have also been positive reports of the NATALEE study. Other clinical studies are currently investigating substances that are already established in the metastatic setting. These include, for example, the DESTINY Breast05 study with trastuzumab deruxtecan and the SASCIA study with sacituzumab govitecan. In this review paper, we summarize and place in context the latest developments over the past months.

Update Breast Cancer 2023 Part 2 - Advanced-Stage Breast Cancer.

In recent years, a number of new therapies have led to advances in the treatment of patients with advanced breast carcinoma. These substances are mainly CDK4/6 inhibitors and other substances that can overcome endocrine resistance, oral selective estrogen receptor degraders, antibody drug conjugates (ADCs), and PARP inhibitors. This review summarizes and evaluates the latest study results that have been published in recent months. This includes the overall survival data of the Destiny-Breast03 study, the first analysis of the CAPItello-291 study, the comparison of CDK4/6 inhibitor treatment with chemotherapy in the first line of therapy (RIGHT Choice study), the first analysis of the Destiny-Breast02 study in the treatment setting after T-DM1 treatment, and the first analysis of the Serena-2 study. Most of these studies have the potential to significantly change the therapeutic landscape for patients with advanced breast carcinoma and show that the continued rapid development of new therapies is always producing new results.

Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study.

BACKGROUND: In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119. METHODS: Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline. RESULTS: HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, -1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points. CONCLUSIONS: HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10.

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.

Differences in patterns of sexual assault among female victims preceding and during the COVID-19 pandemic: an analysis of encounters in an emergency department.

The aim of this study was to evaluate how the COVID-19 pandemic may have impacted the number and patterns of sexual assault victims within a German metropolitan city. A retrospective single center analysis of the gynecology examination reports of all women presenting to the emergency department of a university hospital after a sexual offense between 03/2013 and 02/2021 (n = 1167). Comparison of the first year of the pandemic 03/2000-03/2021) to previous years (03/2017-02/2020) and comparison of periods of government-imposed social distancing (03/12/2020-05/23/2020 and 10/23/2020-02/28/2021) with corresponding periods of pre-pandemic years. The overall number of sexual assault cases did not change during the first year of the COVID-19 pandemic. However, during the stay-at-home orders, the number of women presenting to the emergency department decreased by 38% (n=45 vs. 72). Fewer victims filed a police report during the pandemic (49.5% vs. 73.9%, p<0.001) and the lockdown period (50% vs. 76.5%, p<0.001). Less genital injuries after sexual assault were detected during the pandemic (14.3% vs. 25.2%, p<0.02), but there was an increase of illegal substance abuse (19.5% vs. 9.3%, p<0.003). During the stay-at-home orders fewer victims reported alcohol consumption (42.4% vs. 62.5 %, p<0.023). Despite the decrease in sexual offense related police reports, the number of sexual assault cases remained consistent, and the usage of illegal drugs increased during the COVID-19 pandemic. These findings represent the importance of providing support to sexual assault victims, as well as the implementation of preventative measures, especially in times of crisis.

Update Breast Cancer 2023 Part 3 - Expert Opinions of Early Stage Breast Cancer Therapies.

The St. Gallen (SG) International Breast Cancer Conference is held every two years, previously in St. Gallen and now in Vienna. This year (2023) marks the eighteenth edition of this conference, which focuses on the treatment of patients with early-stage breast carcinoma. A panel discussion will be held at the end of this four-day event, during which a panel of experts will give their opinions on current controversial issues relating to the treatment of early-stage breast cancer patients. To this end, questions are generally formulated in such a way that clinically realistic cases are presented - often including poignant hypothetical modifications. This review reports on the outcome of these discussions and summarises the data associated with individual questions raised.

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis.

Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. Methods: The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Discussion: Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.