BACKGROUND:Despite the declining incidence and mortality of cervical cancer following the introduction of the opportunistic cytological screening, a diagnostic gap persisted, particularly for adenocarcinoma, due to the lower sensitivity of conventional cytology for glandular versus squamous lesions, resulting in a stagnating or modest increase in adenocarcinoma incidence. Since 2020, combined screening with HPV testing and cytology has been recommended in Germany for women aged 35 years and older. METHODS:The present analysis is based on nationwide data from the German Cancer Registry. Women who received the diagnosis of a cervical adenocarcinoma in situ (ACIS) or invasive adenocarcinoma in the years 2016-2022 were included in the analysis. Trends in age-specific and standardized incidence in three age groups (under age 35, age 35-64, and age 65 and above) were analyzed with joinpoint regression. RESULTS:Data on 4128 women with ACIS and 6244 with invasive adenocarcinoma were evaluated. In women aged 35-64, the introduction of combined screening led to a marked increase in ACIS diagnoses (average annual increase, 17.3%; 95% confidence interval [14.9; 19.6]. The rise was particularly large in 2020, with an annual percentage change (APC) of 27.5%, [17.4; 38.5]. Over the same period, there was a decline in invasive adenocarcinomas from 2021 onward (APC -10.8%, [-22.7; 2.8]). The incidence of ACIS also rose among women aged 65 and above, while that of adenocarcinoma fell slightly. CONCLUSION:Combined screening for cervical cancer improved the early detection of preinvasive glandular lesions. There is also evidence for a reduction of invasive disease in the screened population. For the full potential of screening to be achieved, there is a need for quality-assured organized programs and additional biomarkers for HPV-negative adenocarcinoma.
The prognostic and therapeutic roles of biological markers in early-stage breast cancer (eBC) warrant further investigation. Non-Breast Cancer (BRCA) genes, along with moderate-and low-penetrance breast cancer risk variant genes, are crucial for maintaining genome stability, yet their prognostic significance in eBC remains unclear. This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients. Significant correlations were observed between the messenger ribonucleic acid (mRNA) expression levels of the genes Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM was associated with longer metastasis-free survival (MFS). Conversely, lower mRNA expression of BLM correlated with favorable outcomes, particularly in triple-negative tumors. Additionally, high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels. This study highlights the prognostic significance of ATM, BLM, and WRN in predicting survival outcomes in eBC patients. Background: The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer (eBC) remains unclear and warrants further investigation. This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer. Methods: Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid (mRNA) expression levels. Statistical analysis, including Kaplan-Meier curves, univariable, and multivariable Cox regression analyses, was performed to assess metastasis-free survival (MFS) of mRNA expression of non-BRCA genes. Subgroup analyses were also conducted among four different molecular subtypes of eBC. Results: Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM correlated with longer MFS in the entire cohort (p = 0.022, Log Rank), and in luminal-B-like tumors (p = 0.036). Lower mRNA expression of BLM was associated with favorable outcomes (p = 0.011, Log Rank), particularly in triple-negative eBC (p = 0.030, Log Rank). Finally, high levels of WRN mRNA expression correlated with significantly longer MFS compared to low mRNA expression levels (p = 0.009, Log Rank). Conclusions: This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes, such as ATM, BLM, and WRN, for survival outcomes in eBC.
Biomarkers are integral to modern breast cancer management by providing essential information for prognosis and treatment selection. This review presents the 2026 update of the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) on therapy-relevant prognostic and predictive biomarkers. The recommendations are based on a structured evaluation of the most recent and clinically relevant evidence using the AGO grading system to support decision-making in routine clinical practice.
LBA538 Background: This phase III trial is a prospective, randomized, double-blinded, multi-center study (NCT05232916) in HLA-A*02 patients at approximately 140 sites in the US and Europe. A third non-randomized arm of approximately 250 non-HLA-A*02 patients is now fully enrolled and preliminary immune response data is presented below. GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. Methods: After standard of care neoadjuvant and adjuvant therapy, 6 intradermal injections of GLSI-100 will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up. Immune responses to GP2 were measured over time using delayed-type-hypersensitivity (DTH) skin tests and injection site reactions (ISRs). The patient population is defined by these key eligibility criteria: 1) HER2/neu positive and HLA, 2) Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy, 3) Exclude Stage IV, and 4) Completed at least 90% of planned adjuvant trastuzumab-based therapy. Results: All patients (n=247) were vaccinated with GLSI-100. Injection site reactions and erythema (redness) were assessed at various time points and represent an in vivo immune response in patients. The ISR orthogonal mean was measured 48-72 hours following vaccination with GLSI-100. For GP2 treated patients, there was a significant increase in the percentage of patients experiencing ISRs in the 4th, 5th or 6th vaccination compared to the ISRs from the 1st vaccination. In this preliminary analysis, the frequency of ISRs increased significantly from 20.2% of the patients experiencing an ISR after the first vaccination to 55.3% of the patients experiencing an ISR after the 4th, 5th or 6th vaccination (McNemar p < 0.001). The study is ongoing and data collection and cleaning continue, so final results may vary. Conclusions: Preliminary injection site reaction data comparing vaccination over time in GLSI-100 treated non-HLA-A*02 patients showed a significant increase in immune response. Future studies may explore the use of immune responses to assess correlation of DTH to ISRs, immunogenicity of GLSI-100 by specific HLA type, timing of boosters to sustain immunity, clinical site performance, and the discontinuation of treatment for non-responders. Funding: This trial is supported by Greenwich LifeSciences. Clinical trial information: NCT05232916 .
The German Guideline Committee (AGO: Working Group on Gynecologic Cancers) updated its yearly recommendations on the diagnosis and treatment of breast cancer in March 2026. Chapters on oncological and oncoplastic-reconstructive surgery are coordinated with the Working Group for Plastic, Aesthetic, and Reconstructive Surgery in Gynecology (AWOgyn). The most important changes include the ommission of sentinel lymph node biopsy (SLNB) and preffered axillary staging in patients with node-positive breast cancer undergoing neoadjuvant chemotherapy (NACT). Targeted axillary dissection (TAD) is endorsed as the method of choice [AGO ++] in patients converting from cN + to ycN0 status, and other de-escalated techniques (SLNB, target lymph node biopsy [TLNB]) are also possible options [AGO +]. Following NACT, ALND is indicated only when macrometastatic disease is detected in the sentinel and/or in the target lymph node.
The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2026 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.
Several studies have compared validated tracers, such as the radioactive tracer technetium-99m nanocolloid (99mTc-nanocolloid) and superparamagnetic iron oxide (SPIO), for sentinel node biopsy (SNB) in early-stage breast cancer (eBC). These studies mostly investigated the differences in detection rate and SNB-related adverse events. The aim of our study was to determine whether there are any crucial differences between the two procedures, including the duration of surgery and the number of detected sentinel lymph nodes (SN), which may affect patient treatment and the standard of care in eBC. All patients were treated at the University Medical Centre Mainz by certified breast surgeons. Two consecutive groups of patients were identified based on the injected tracer: Technetium Group (N=517), patients treated from January 1 2017 to December 31 2019, with 99mTc-nanocolloid as tracer and SPIO Group (N=456), patients treated from January 1 2020 to December 31 2022, with superparamagnetic iron oxide particles as ferromagnetic tracer. To avoid potential bias, we performed propensity score matching. After performing propensity score matching, the total surgery time was significantly shorter in the Technetium Group compared to the SPIO Group [64 (48 - 84) vs. 71.5 (58 - 98) minutes; p<0.001]. Both groups did not differ regarding detection rates, or complications (p>0.05). The median number of removed SN was 1.0 in the 99mTc-nanocolloid Group and 2.0 in the SPIO Group. In conclusion, our analysis showed that the use of 99mTc- nanocolloid for SNB resulted in shorter operation time and removal of less SN compared to the SPIO intervention.
OBJECTIVE:Frailty, nutritional deficiencies, and anemia frequently coexist in gynecologic cancer and may adversely influence clinical outcomes. This study aimed to evaluate the prognostic value of the G8 geriatric screening tool (G8) for survival outcomes in patients undergoing gynecologic oncology surgery, with postoperative complications and selected modifiable preoperative conditions assessed as secondary outcomes. METHODS:Patients ≥60 years undergoing gynecologic oncology surgery were prospectively screened for frailty between May 2020 - June 2025. Survival was evaluated with Kaplan-Meier curves and Cox regression. Propensity score matching included demographics, comorbidities, and tumor characteristics; matched samples were analyzed using weighted Cox models. RESULTS:Of 257 screened patients, 180 were included (endometrial n = 72, ovarian n = 71, vulvar n = 26, cervical n = 6, vaginal cancer n = 5; mean age 69.6 ± 7.9 years; follow-up 25.1 ± 16.3 months). G8 positive patients (≤14 points) had more comorbidities and were more likely to present with preoperative anemia, hypoalbuminemia, and vitamin D or B12 deficiency. FIGO stages, surgical approach and postoperative complications were comparable. G8 positive patients were less likely to receive standard adjuvant therapy (p = 0.003). In matched analyses, G8 positivity remained significantly associated with reduced progression-free survival (HR: 1.87, 95% CI: 1.01-3.49, p = 0.047) and showed a trend toward worse overall survival (HR: 2.25, 95% CI: 0.98-5.16, p = 0.055). Surgical resection status was the strongest predictor of oncological outcome. CONCLUSIONS:A low preoperative G8 score was associated with reduced progression-free and potentially worse overall survival in older women with gynecologic tumors. The G8 may help identify modifiable factors such as anemia or vitamin D deficiency, while complete tumor resection remained the strongest prognostic factor.
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy are the preferred choice for first-line treatment of patients with HR+/HER2- locally advanced/metastatic breast cancer (aBC). The CDK4/6i ribociclib in combination with an aromatase inhibitor (AI) or fulvestrant (FUL) has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits for pre- and postmenopausal aBC patients who were enrolled in the three pivotal MONALEESA trials. Following the initial approval of ribociclib in 2017, the non-interventional RIBANNA study was initiated to evaluate the effectiveness and safety of ribociclib plus AI/FUL therapy among patients with aBC in a real-world setting. Two additional treatment cohorts (endocrine monotherapy [ET] and chemotherapy [CT]) were included to extend the knowledge about current aBC treatments. A total of 2567 patients were enrolled in 279 study centers, of whom 1852 were treated with ribociclib+AI/FUL, 183 were treated with ET, and 139 were treated with CT, who were available for effectiveness analyses. Median PFS (mPFS) and median OS (mOS) on first-line treatment with ribociclib+AI/FUL were 35.0 and 76.0 months, respectively. Adjustment for differences in demographic and baseline characteristics resulted in a longer mPFS on ribociclib+AI/FUL (34.7 months) compared to ET (26.4 months) or CT (19.2 months). Adverse events (AEs) on ribociclib were consistent with those seen in the pivotal trials, and no new safety signals were observed. The RIBANNA study confirmed the PFS and OS benefit seen in the MONALEESA trials. Together with the safety data, this large real-world dataset supports the favorable risk/benefit profile of ribociclib in large scale patient populations.
Background:Superparamagnetic iron oxide (SPIO) tracers offer a radiation-free technique for sentinel lymph node biopsy (SNB) in early breast cancer (eBC). However, the data on optimal administration in daily practice, such as the optimal tracer volume and injection method, are still lacking. Methods:In this real-world data analysis, patients with clinically node-negative eBC who underwent SNB with SPIO (Magtrace®) between January 2020 and December 2022 were included. Primary endpoint was the impact of tracer volume on the detection rate. Secondary endpoints evaluated number of removed sentinel lymph nodes, surgical time, and the impact of tracer timing and body mass index (BMI) on detection rate. Results:A total of 456 patients were included in the study. Overall, 223 patients received 1 mL and 232 patients 2 mL of SPIO. The median time of tracer application was 4 days. Detection rates were similar between both groups (95.5% for 1 mL vs. 96.1% for 2 mL; p = 0.707), with a median of 2.0 sentinel nodes removed in both groups (p = 0.205). The median time of surgery was 70 min in the 1 mL group and 72 min in the 2 mL group, p = 0.972. The detection rate was 97.3% and 95.3% when tracer was injected before and after the median time of application, respectively (p = 0.286). BMI of ≥25 kg/m2 led to a detection rate of 94.9% in the 1 mL group and 94.2% in the 2 mL group (p = 0.520). Conclusions:In this large real-world analysis, 1 mL and 2 mL were similar in the clinical performance of SNB in eBC. High detection efficacy was found regardless of tracer timing and BMI. This real-world analysis reinforces SPIO's role as an effective and adaptable alternative to conventional tracers in SNB for eBC.