Purpose : Breast cancer (BC) patients with pathogenic germline BRCA1/2 mutations ( gBRCA1/2mut) have a substantially increased risk of ovarian cancer (OC). Risk-reducing bilateral salpingo-oophorectomy (RRSO) remains the only effective preventive strategy. However, data on the utilization and optimal timing of this procedure in g BRCA mut BC patients are limited. Methods : This retrospective study included 148 patients with gBRCA1/2mut BC treated at the Hereditary Breast and Ovarian Cancer Center, University Hospital Erlangen, between 2012 and 2024. Clinical, pathological, treatment-related, and genetic data were collected and analyzed from electronic records. Results : In this cohort of 148 patients with gBRCAmut BC, 60.1% harboured a gBRCA1 and 39.9% a gBRCA2 mutation. BC was diagnosed at the mean age of 47.1 years, 73.6% presenting at UICC stage I–II. 38.4% Patients were diagnosed with a hormone receptor–positive BC, 8.9% with HER2-positive BC and 47.9% triple-negative BC. 101 patients (68.2%) additionally underwent RRSO, predominantly within 12 months of BC diagnosis. Occult OC was detected in three patients (2.9%) at the time of RRSO during BC follow up, while 4 patients without RRSO (8.5%) were diagnosed with OC after BC. Conclusions : In real-world setting, RRSO is a common prevention in g BRCA mut BC follow up. The majority of patients undergo surgery within the first two years following a BC diagnosis. Survival outcomes among patients with BC have improved substantially in recent years. Consequently, the risk of developing OC in g BRCA mut individuals carrying remains high. RRSO should therefore continue to be discussed with patients, even in the context of a BC diagnosis, as a strategy for OC prevention.

Germline BRCA1 and BRCA2 mutations enable targeted therapies in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). The two poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors olaparib and talazoparib were introduced into clinical practice in 2018. Limited evidence about their routine clinical use highlights the importance of this analysis. We provide a real-world analysis for PARP-inhibitor use in ABC patients treated within the prospective German PRAEGNANT registry (NCT02338167). 152 patients with ABC receiving a PARP-inhibitor were included. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated for all patients using the Kaplan-Meier method. Subgroups (line of therapy, metastasis timing, hormone receptor (HR) status, treatment: olaparib, talazoparib, among others), germline BRCA1, BRCA2 and PALB2 mutations and adverse events (AEs) were analyzed. The median rwPFS was 6.2 months (95% CI, 4.8-7.9) and the median rwOS was 17.1 months (95% CI, 14.4-22.3). Line of therapy, HR status and treatment (olaparib versus talazoparib) appeared to especially affect both rwPFS and rwOS. Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.

Abstract Purpose Ovarian cancer is frequently associated with gBRCA1/2 mutations, which also confer a high lifetime risk of breast cancer in non-affected patients. While risk-reducing salpingo-oophorectomy (RRSO) is established in hereditary breast and ovarian cancer prevention, the recommendation for risk-reducing bilateral mastectomy (RRBM) remains unclear in gBRCA1/2mutovarian cancer patients due to high recurrence rates and limited survival. This study evaluates the preventive strategies of these patients in a real-world setting. Methods This retrospective study included 49 patients with gBRCA1/2mut HGSC treated at the Hereditary Breast and Ovarian Cancer Centre, University Hospital Erlangen, between 2012 and 2024. Clinical, pathological, treatment-related, and genetic data were collected and analyzed from electronic records. Results Among 49 patients with gBRCAmut HGSC, 44 out of 49 did not undergo a RRBM during follow-up. Intensified breast cancer surveillance was recommended to 33 patients. Although 19 out of 49 patients were formally recommended a RRBM, only two proceeded with the preventive option. Three additional patients chose the surgery driven by the diagnosis of metachronous breast cancer. 80% of the operations occurred > 60 months after ovarian cancer diagnosis. Conclusions In patients with gBRCA1/2mut and a history of HGSC, RRBM is rarely chosen. Most patients prefer an intensified surveillance program. Due to low metachronous breast cancer rate in follow up care, RRBM seems to be an option just for long-term survivors. Individual patient preferences play a crucial role in the management strategy.

Abstract Background Nipple discharge is one of the most common breast complaints, reported by 80% of women outside the breastfeeding period. It may result from physiological or pathological causes, including intraductal papillomas, ductal carcinoma in situ (DCIS), or invasive breast cancer (BC). This study aimed to evaluate the incidence of malignant upgrades following microdochectomy for nipple discharge and investigate the predictive value of nipple discharge characteristics, in a German population. Methods A total of 115 patients with unilateral nipple discharge that underwent microdochectomy from 2019 to 2023 were followed up retrospectively. A standardized diagnostic algorithm was applied, including imaging (mammography, ultrasound), cytological examination of nipple discharge, and histopathological assessment of surgical specimens. We investigated the malignant upgrade after microdochectomy, and the association of different colors of nipple discharge with DCIS and invasive BC. Results Histopathology revealed DCIS in 7 cases (6.1%), with concomitant invasive BC in 3 cases (2.6%). Bloody nipple discharge was the most frequent symptom (85.7%) of malignant upgrade cases. However, the rate of malignancy did not significantly differ across discharge types (p = 0.442, Fisher’s exact test). All detected invasive BCs were hormone receptor positive, Human epidermal growth factor receptor 2 (HER2/neu) negative, with early-stage tumors (UICC stage IA). Preoperative cytology demonstrated limited sensitivity, with only one of four analyzed malignant cases showing suspicious findings. Conclusions Microdochectomy remains a valuable diagnostic and therapeutic tool for patients with unilateral nipple discharge with unsuspicious preoperative breast imaging. The rate of newly detected BC in our study population was low. However, the preoperative identification of patients with increased risk of malignancy stays challenging. Emphasis for future research should be placed on identifying patients with the highest risk for BC e.g. bloody and clear pathologic nipple discharge.

Abstract Increased radiosensitivity can cause adverse radiotherapy effects. Heterozygote variants in breast cancer risk genes increase cancer risk and may affect radiosensitivity. This study assessed their impact on individual radiosensitivity to determine the radiation risk for gene carriers. Radiosensitivity was analyzed in 273 patients with breast cancer risk gene variants. Using fluorescence in situ hybridization (FiSH), chromosomal aberrations were quantified as breaks per metaphase (B/M) after ex vivo irradiation of blood lymphocytes. Results were compared with healthy controls and breast cancer cases, both without confirmed non-carrier status, limiting gene-specific conclusions. Gene carriers showed slightly increased radiosensitivity (mean 0.488 B/M ± 0.134) compared with healthy controls (0.411 B/M ± 0.088; p < 0.0001) but similar to breast cancer control group (0.498 B/M ± 0.192; p = 0.563). In BRCA1/2 carriers, radiosensitivity was slightly increased, while single cases in BARD1, RAD51, and MSH variants suggested a possible increase (p < 0.003). Radiosensitivity was influenced by gene locus, variant type, age, and cancer history. 24.5% of carriers exceeded a cutoff of ≥ 0.55 B/M, where dose reduction could be considered. Radiosensitivity of breast cancer risk gene carriers varies and is slightly increased. Individuals with increased radiosensitivity risk should consider testing.

A relevant proportion of malignancies predominantly or exclusively affecting women, including breast and gynecologic cancers, is attributable to hereditary tumor syndromes, profoundly impacting cancer risk, prognosis, and therapeutic management. Today, the routine use of comprehensive germline panels has shifted the focus from solely pathogenic BRCA1/2 variants to include numerous pathogenic variants of other high- and moderate-risk genes. A broad spectrum of genetic alterations has been identified as causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC), encompassing not only BRCA1 and BRCA2, but also PALB2, ATM, BARD1, CHEK2, BRIP1, RAD51C, and RAD51D. Beyond HBOC, numerous additional hereditary tumor syndromes are of significance in senologic and/or gynecologic oncology, including Li-Fraumeni syndrome, Lynch syndrome, DICER1 syndrome, Hereditary Diffuse Gastric Cancer, Neurofibromatosis type 1, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, Tuberous Sclerosis, and pathogenic variants in NBN and SMARCA4. Affected individuals are offered specialized surveillance to enable early detection or even prevention of cancer. In addition to regular clinical examinations and imaging, preventive strategies may include risk-reducing surgery. Pathogenic germline variants also influence therapeutic management of cancer patients. For specific indications, targeted therapies are available, for example PARP [poly (ADP-ribose) polymerase] inhibitors for pathogenic BRCA variant carriers across multiple tumor entities. Optimal management requires interdisciplinary coordination, encompassing genetic counseling, early detection, and risk-reducing strategies within specialized centers. This review provides a comprehensive overview of hereditary tumor syndromes predisposing to breast and gynecologic malignancies, with a focus on genetic basis, associated cancer risks, and implications for clinical management. By delineating these syndromes, it aims to assist clinicians in recognizing hereditary cancer predisposition and in guiding affected individuals within routine senologic and gynecologic practice.

BACKGROUND/AIM:Biopsy of suspicious microcalcifications (MC) detected in breast cancer screening yields benign results in the majority of cases, resulting in a substantial number of avoidable interventions. While magnetic resonance imaging (MRI) demonstrates high accuracy for invasive breast cancer, its diagnostic value for precancerous lesions remains uncertain - particularly in average-risk screening populations. This study aimed to assess the diagnostic performance of an abbreviated breast MRI reading protocol in a screening-like cohort. PATIENTS AND METHODS:In this prospective single-center study, 58 women (mean age 58±24 years) with 59 suspicious MC on full-field digital mammography (FFDM) were included. A total of 68 lesions underwent histopathological verification. MRI datasets were independently assessed by four radiologists (5-15 years of experience), blinded to mammographic findings, using a standardized abbreviated protocol including maximum intensity projection (MIP), early post-contrast subtraction, and native images. RESULTS:Among 59 microcalcification lesions, 21 were malignant and 38 benign. Sensitivity ranged from 74% to 83%, specificity from 58% to 83%, positive predictive value from 56% to 75%, negative predictive value from 83% to 86%, and accuracy from 68% to 81%. No invasive carcinomas were missed by any reader. False-negative findings were exclusively ductal carcinoma in situ (DCIS). Mean reading time ranged from 1 min 42 sec to 3 min 26 s. MIP-only evaluation demonstrated markedly lower sensitivity (48-52%) despite higher specificity (83-94%). Interreader agreement for the final recall decision was moderate (Fleiss' κ=0.47), with pairwise Cohen's κ values ranging from 0.40 to 0.53. CONCLUSION:Abbreviated breast MRI is a feasible and time-efficient approach with consistent diagnostic performance across readers for evaluating suspicious MC, further evaluation as screening tool is needed. MIP-only evaluation, does not appear to provide sufficient diagnostic reliability.

PurposeMutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant was the first approved PI3K inhibitor and was introduced in clinical practice in 2019. A lack of evidence for the use of alpelisib in the context of current treatment options like cyclin-dependent 4/6 inhibitor (CDK4/6i), highlights the importance of this analysis. We provide a real-world analysis of the use of alpelisib with the prospective German PRAEGNANT registry (NCT02338167).Methods57 patients with advanced breast cancer receiving alpelisib and fulvestrant were identified. 55 Patients had received prior CDK4/6i therapy. Progression-free survival (PFS) and overall survival (OS) were calculated for all patients, and stratified according CDK4/6i pre-treatment, using the Kaplan-Meier method. Subgroups (age, line of therapy, concomitant disease among others), somatic PIK3CA mutations, reasons for discontinuation and adverse events (AEs) were analyzed.ResultsThe median PFS was 5.0 (95% confidence interval [CI], 3.1-9.4) months, and the median OS was 20.1 (95% CI, 14.6-30.8) months. Line of therapy and concomitant diseases appeared to affect PFS, while the line of therapy and preexisting diabetes influenced OS. However, subgroups were too small for statistical testing. Discontinuation was mainly due to tumor progression (56.1%). Hyperglycemia, rash and diarrhea were the most documented AEs.ConclusionThis prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.

Background:The introduction of oral anticancer therapies has, at least partially, shifted treatment from clinician-supervised hospital care to patient-managed home regimens. However, patients with breast cancer receiving oral cyclin-dependent kinase 4/6 inhibitor therapy still require regular hospital visits to monitor side effects. Telemonitoring has the potential to reduce hospital visits while maintaining quality care. Objective:This study aims to develop a digital home-based health care center (DHHC) for acquiring electrocardiograms (ECGs), white blood cell (WBC) counts, side effect photo documentation, and patient-reported quality of life (QoL) data. Methods:The DHHC was set up using an Apple Watch Series 6 (ECG measurements), a HemoCue WBC DIFF Analyzer (WBC counts), an iPhone SE (QoL assessments and photo documentation), a TP-Link M7350-4G Wi-Fi router, and a Raspberry Pi 4 Model B. A custom-built app stored and synchronized remotely collected data with the clinic. The feasibility and acceptance of the DHHC among patients with breast cancer undergoing cyclin-dependent kinase 4/6 inhibitor therapy were evaluated in a prospective, single-arm, monocentric study. Patients (n=76) monitored side effects-ECGs, WBC counts, photo documentation, and QoL-at 3 predefined time points: study inclusion (on-site), day 14 (remote), and day 28 (remote). After the study completion, patients completed a comprehensive questionnaire on user perception and feasibility. Adherence to scheduled visits, the success rate of the data transfer, user perception and feasibility, and the clinical relevance of remote measurements were evaluated. Results:Mean adherence to the planned remote visits was 63% on day 14 and 37% on day 28. ECG measurements were performed most frequently (day 14: 57/76, 75%; day 28: 31/76, 41%). The primary patient-reported reason for nonadherence was device malfunction. The expected versus the received data transfer per patient was as follows: ECGs: 3 versus 3.04 (SD 1.9); WBC counts: 3 versus 2.14 (SD 1.14); QoL questionnaires: 3 versus 2.5 (SD 1.14); and photo documentation: 6 versus 4.4 (SD 3.36). Among patients, 81% (55/68) found ECG measurements easy, 82% (55/67) found photo documentation easy, and 48% (33/69) found WBC measurements easy. Additionally, 61% (40/66) of patients felt comfortable with self-monitoring and 79% (54/68) were willing to integrate remote monitoring into their future cancer care. Therapy-induced decreased neutrophil count was successfully detected (P<.001; mean baseline: 4.3, SD 2.2, ×109/L; on-treatment: 1.8, SD 0.8, ×109/L). All-grade neutropenia and corrected QT interval prolongations were detected in 80% (55/68) and 2% (1/42) of patients, respectively. Conclusions:Adherence to scheduled remote visits was moderate, with nonadherence primarily attributed to device-related complications, which may have also affected the success rate of data transfer. Overall, patients considered remote monitoring useful and feasible. The prevalence of reported adverse events was comparable to existing literature, suggesting clinical potential. This initial feasibility study highlights the potential of the DHHC.

Background Breast cancer is the most common cancer in women, with early detection significantly improving outcomes. Heat flow imaging (HFI) is a non-invasive dynamic thermography method with prior tissue cooling. It has shown its potential as an additional diagnostic tool. The aim of the present study was to evaluate the feasibility of diagnostic HFI in patients with palpable breast lesions during outpatient visits. Methods The patients presenting with palpable breast lesions at the Erlangen University Hospital were recruited between November 2023 and April 2024. Heat flow imaging was performed in addition to sonographic and mammographic imaging in routine care. Additionally, the patients completed a pain questionnaire to evaluate the comfort of the procedure. We used a two-phase study design. During the first phase, the imaging procedure was established and standardized. In the second phase, imaging footage was compared with conventional mammography, sonography, and histological findings. Results Thirty-nine patients were recruited and 18 patients underwent final evaluation. Heat flow imaging successfully detected 7 out of 11 palpable carcinomas. Factors contributing to missed lesions and impairing image quality were inadequate cooling or improper camera positioning. The mean pain score reported during the procedure was 0.7 on a visual analog scale from 0 to 10, indicating minimal discomfort. Conclusions Heat flow imaging is a feasible imaging method that may serve as a supplementary diagnostic tool for breast cancer detection in patients with palpable breast lesions. However, it is still considered an experimental method and its use should be limited in the context of clinical trials. Further research involving larger patient groups is required to validate these preliminary findings and to optimize image acquisition protocols.

Assessment of breast volume has a relevance for aesthetic surgery and for the prevention and prediction of breast diseases. This study investigated breast volume measurements using a three-dimensional (3D) body surface scanner integrated in a smartphone device in comparison with magnetic resonance imaging (MRI) scans. Breast volume was assessed for 22 women who underwent routine MRI imaging. 3D surface images were acquired using a smartphone’s digital texture camera (iPhone 11 Pro Max, Apple, California, USA, 2019). Breast volumes were manually outlined and calculated by two independent investigators using a 3D software tool (Meshmixer 3.5, Autodesk, Inc., 2018). Volume assessments from MRI images were performed by a radiologist using Syngo.via (Siemens Healthcare, Erlangen, Germany, VB50). The agreement between both methods and the inter-observer agreement was calculated with the concordance correlation coefficients and analysed with Bland–Altman plots. The mean breast volume as determined by MRI volumetry was 771.0 ml on the left side and 763.9 ml on the right side. Utilizing the 3D body surface volume assessment method, the mean breast volume was measured as 660.3 ml (observer A) and 616.8 ml (observer B) on the left side, and 701.9 ml (observer A) and 638.6 ml (observer B) on the right side. Although a high correlation was observed, differences in volume measurements appeared more pronounced in cases of larger breast volume. Smartphone-based 3D assessment of breast volume sufficiently agreed with MRI-based breast volume. This new technique could be used for cosmetic breast assessments in a surgical context and possibly in breast cancer risk studies assessing breast volume as outcome parameters.

Unclear or suspicious breast findings are typically clarified by interventional breast biopsy. Lesions with uncertain malignant potential are grouped as B3 lesions in histopathology. The B3 group according to the European Working Group for Breast Screening Pathology (EWGBSP) comprises various breast lesions with different upgrade rates to invasive breast cancer (BC) or ductal carcinoma in situ (DCIS) if surgical removal is performed. The objective of this study was to investigate malignant upgrade rates to DCIS and/or invasive breast cancer (BC) after open surgical excision for the different B3 lesions. A total of 192 patients with histologically verified B3 lesions were followed up retrospectively for this analysis. Patients with the B3 lesions atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and classical lobular neoplasia (LN1-2) were combined into one group, while cellular fibroepithelial lesions (CFL) and phyllodes tumors without suspicion of malignancy, as well as papillomas and radial scars/complex sclerosing lesions (RS/CSL) were summarized in two other groups. We investigated the association of the different B3 lesions with invasive BC or DCIS after open surgical excision. Histopathological investigation revealed in 21 (10.9

INTRODUCTION:Whereas CDK4/6 inhibitors (CDK4/6i) are the standard first-line therapy for patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer, guidelines on treatment options after progression on CDK4/6i are more diverse. Chemotherapy is recommended if a patient develops endocrine resistance or experiences a visceral crisis. However, the impact of the choice of chemotherapy remains unknown. METHODS:HRpos/HER2neg patients who received first-line CDK4/6i, followed by second-line chemotherapy (N = 215) were selected from the prospective PRAEGNANT registry (NCT02338167). Cox regression analyses were used to evaluate the correlation between the choice of chemotherapy (capecitabine monotherapy, capecitabine + bevacizumab, taxane monotherapy, taxane + bevacizumab, anthracycline, other chemotherapeutics) and progression-free survival (PFS) and overall survival (OS). RESULTS:Patients who received second-line chemotherapy mostly had high-grade tumors (G2: 62.3 %, G3: 33.3 %), visceral metastases (62.3 %) and developed metastatic disease following a primary breast cancer diagnosis (73.8 %). Capecitabine was the most common regimen (25.1 %), followed by taxane + bevacizumab (17.2 %). When adjusting for other prognostic factors (age, BMI, grading, ECOG, metastasis group and time to metastases), the choice of chemotherapy did not influence PFS (p = 0.16) nor OS (p = 0.47). Adjusted hazard ratios for PFS were lowest in regimens with bevacizumab (capecitabine as reference; capecitabine + bevacizumab: 0.53 (95 %CI: 0.29, 0.97); taxane + bevacizumab: 0.64 (95 %CI 0.35, 1.15)). CONCLUSION:Although the choice of chemotherapy post-CDK4/6i did not significantly affect PFS or OS, combinations with bevacizumab may have some benefit. Nevertheless, considering side effects may be most important when choosing the type of second-line chemotherapy.

As a result of advancements in the diagnosis and therapy of cancer, the prognosis for cancer patients has significantly improved. The benefits of a significantly enhanced survival time lead to a more extensive concern with quality of life and managing the side effects during oncological treatment. Implementing integrative medicine strategies has been found to reduce the side effects of therapy and disease. In 2021 the S3 guideline on complementary medicine in oncology was published for the first time, which takes a stand on the most common aspects of complementary and integrative medicine in Germany. The aim was to see whether a previous healthy life style impacts the success of integrative medicine for patients. Within the framework of a cross-sectional study over 15 months, 120 cancer patients were monitored at a standardized integrative medicine consultancy service at the University Integrative Medicine Center of the University Hospital Erlangen, Department of Gynecology and Obstetrics. The basic questionnaire consisted of questions on socioeconomic background information, lifestyle factors, such as dietary habits or smoking behavior, as well as information on the gynecological situation. Furthermore, an evaluation based on patient-reported therapy goals concerning the reduction of side effects of conventional cancer treatments, enhancement of disease-related quality of life and better stress and disease management, active participation in cancer treatments, mind–body stabilization, and improvements in coping strategies were assessed. In addition, the impact of patient characteristics and lifestyle on the subjective achievement of these outcomes was evaluated to set the answers in context and show its influence. Statistical analysis was performed using SPSS Statistics for Windows version 26 (IBM Corporation, Armonk in New York, USA). Mean, standard deviation, minimum, and maximum were calculated for age and BMI. The other characteristics regarding demographics, lifestyle, tumor disease, and therapy were analyzed based on their respective absolute and relative frequencies. A large majority of the patients' participation goal was to reduce cancer-related side effects (90.8

Introduction Genetic mutations contribute to around 10% of breast and 25% of ovarian cancers, with one third of patients having a familial cancer history. The German Consortium for Familial Breast and Ovarian Cancer (DK-FBREK) was founded in 1996 to improve care for these patients. Certification of cancer centers, introduced in 2004, has been linked to improved survival rates and ensures adherence to evidence-based standards. This study investigates changes in care structures and quality before and after the initial certification of the HBOC center at the University Hospital Erlangen, certified from 2021 on. Methods This retrospective study analyzed patient data from January 2018 to December 2023 at the certified Hereditary Breast and Ovarian Cancer (HBOC) center at the University Hospital Erlangen. Eligibility for genetic counseling and germline testing followed the German Cancer Society criteria. After informed consent, Next Generation Sequencing (NGS) was performed, and variants were classified according to Human Genome Variation Society (HGVS) and American College of Medical Genetics and Genomics (ACMG) standards. Medical histories and genetic results were recorded in electronic case report forms. Results From 2018 to 2023, a total of 2,694 genetic tests were performed, increasing from 962 pre-certification to 1,732 post-certification (+ 180%). Testing among affected female patients doubled. Genetic testing in breast cancer patients increased from 551 to 1,104, while testing for ovarian carcinoma rose from 117 to 159. Variants of uncertain significance were identified in approximately 9% of cases during both periods. Pathogenic findings were observed in 14.3% of cases pre-certification (with 9.2% involving BRCA1/2 mutations) and 11.5% post-certification (6.4% BRCA1/2 mutations). Enrollment in the intensified surveillance program (IBCS) increased by 182.5%, accompanied by a rise in recommendations for risk-reducing surgeries. Conclusions Certification of medical institutions ensures high-quality, evidence-based patient care and increases the utilization of preventive and counseling services, particularly for HBOC. It strengthens patient trust and acceptance, even in the context of healthcare reforms. Further studies are needed to confirm the long-term impact and necessity of certification.

Patients with hormone receptor‐positive (HRpos), HER2‐negative (HER2neg) breast cancer (BC) benefit less from neoadjuvant chemotherapy (NACT) than patients with triple‐negative and HER2‐positive BC. In this retrospective analysis of the phase IV PreFace clinical trial (NCT01908556), where postmenopausal HRpos BC patients ( n = 3297) were treated with 5‐year upfront adjuvant letrozole therapy, we evaluated the prognosis of patients treated with adjuvant versus neoadjuvant chemotherapy in HRpos/HER2neg early‐stage BC. HRpos/HER2neg patients with information on (neo)adjuvant chemotherapy ( n = 2895) were retrospectively selected from all patients enrolled in the PreFace trial. Invasive disease‐free survival (iDFS) and overall survival (OS) were compared between patient groups that were treated with neoadjuvant or adjuvant chemotherapy. Chemotherapy was given to 1051 patients (36.3% of all patients), of which 874 (83.2%) received adjuvant chemotherapy and 177 (16.8%) NACT. Pathologic complete response (pCR) rate in the NACT group was 6.9%. Patients treated with NACT had a worse outcome than those treated with adjuvant chemotherapy (5‐year iDFS rate 81% vs. 88%; 5‐year OS rate 89% vs. 93%). This effect was maintained after adjusting for age, BMI, lymph node status, grading, tumor size, and histology (hazard ratio for iDFS: 1.95 (95%CI: 1.28–2.95); hazard ratio for OS: 2.13 (95%CI: 1.24–3.66)). Further adjustment for taxane‐based regimes did not alter results. In conclusion, in this retrospective analysis of patients with early‐stage HRpos/HER2neg BC, patients with NACT had a more unfavorable prognosis than patients treated adjuvantly, independent of patient and tumor characteristics. Prognosis of neoadjuvant patients might be affected by resistance mechanisms, warranting further investigation.

Für Patientinnen wie auch Patienten mit hormonrezeptorpositivem (HRpos)/Human epidermal growth factor receptor 2- negativem (HER2neg) Mammakarzinom wurden in den letzten Jahren einige neue, zielgerichtete Therapien eingeführt. Einige dieser Behandlungen konnten sich nicht nur als neuer Therapiestandard etablieren, sondern führten auch zu einem signifikant verlängerten Gesamtüberleben. Insbesondere die Cyclin-dependent Kinase 4 and 6 Inhibitors (CDK4/6i) haben sich als Therapiestandard in der ersten Therapielinie etabliert. Insgesamt 70–80 % der Patientinnen werden mit einem CDK4/6i behandelt. Sowohl für die CDK4/6i als auch für die endokrinen Kombinationspartner wurden in den letzten Jahren zunehmend Biomarker beschrieben, die mit einem Progress oder einer klonalen Selektion oder Evolution assoziiert sind. Vor diesem Hintergrund ist die Kenntnis um Effektivitäts- und Resistenzmechanismen von besonderer Bedeutung. Dieses Wissen könnte wegweisend sein, um die effektivsten Sequenzen zu planen und molekulare Grundlagen für das Überwinden der endokrinen Resistenz zu nutzen. Eine der Studien, die mit einer großen Fallzahl dazu beitragen soll, diese Mechanismen zu erforschen, ist die Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC)-Studie. Diese Übersichtsarbeit fasst den aktuellen Stand der klinischen Forschung zur Resistenz gegen endokrine Therapien mit Fokus auf CDK4/6-Inhibitoren zusammen und erörtert aktuelle Studienkonzepte.