Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [⁶⁸Ga]RM2 has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status. This study assessed tumor visualization by [⁶⁸Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Methods: This retrospective pilot study included eight female patients with initial ER-positive, pre-treated BC who underwent [⁶⁸Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [⁶⁸Ga]RM2 PET/CTs were visually analyzed by two nuclear medicine specialists in consensus. Tumor manifestations were rated qualitatively (i.e., RM2-positive or RM2-negative) and quantitatively using the maximum standardized uptake value (SUVmax). SUVmax values were compared between the two subgroups (RM2-positive vs. RM2-negative). Results: Strong RM2 binding was found in all metastatic lesions of six patients (75%), whereas tracer uptake in all metastases of two patients (25%) was rated negative. Mean SUVmax of RM2-positive metastases with the highest SUVmax per patient (in lymph node and bone metastases; 15.8 ± 15.1 range: 3.7–47.8) was higher than mean SUVmax of the RM2-negative metastases with the highest SUVmax per patient (in bone metastases; 1.6 ± 0.1, range 1.5–1.7). Conclusions: Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [⁶⁸Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. Further studies with larger patient cohorts are warranted to confirm these findings.

Breast cancer (BC) represents the most common type of cancer in females worldwide. Endocrine therapy evolved as one of the main concepts in treatment of hormone-receptor positive BC. Current research focuses on the elucidation of tumour resistance mechanisms against endocrine therapy. In a translational in vitro approach, potential regulatory effects of clinically implemented BC anti-oestrogens on ERα, its coactivators DDX5, DDX17 and other DEADbox proteins as well as on the proliferation markers cyclin D1 and Ki67 were investigated on both the RNA and protein level. BC in vitro models for hormone-receptor positive (MCF-7, T-47D) and hormone-receptor negative cells (BT-20) were subjected to endocrine therapy. Anti-oestrogen-dependent expression regulation of target genes on the transcriptional and translational level was quantified and statistically assessed. Endocrine therapy decreases the expression levels of Ki67, cyclin D1 and ERα in hormone-receptor positive cells. In the hormone-receptor negative cells, the three parameters remained stable after endocrine therapy. Endoxifen triggers a downregulation of DDX5 and DDX23 in MCF-7 cells. Fulvestrant treatment downregulates the expression levels of all investigated DEADbox proteins in MCF-7 cells. In T-47D cells, endoxifen and fulvestrant lead to a decrease of all target gene expression levels. Interestingly, endocrine therapy affects DEADbox RNA expression levels in BT-20 cells, too. However, this result could only be confirmed for DDX1, immunocytologically. The investigated DEADbox proteins appear to correlate with the oestrogen-dependent tumourigenesis in hormone-receptor positive BC and show expression alterations after endocrine treatment.

Background: The quest to comprehend the real-world efficacy of CDK4/6 inhibitors (CDKis) in breast cancer continues, as patient responses vary significantly. Methods: This single-center retrospective study evaluated CDKi use outside the trial condition from November 2016 to May 2020. Progression-free survival (PFS), time-to-treatment failure (TTF), short-term and prolonged treatment benefit (≥4 and ≥10 months), as well as prognostic and predictive markers were assessed with Kaplan–Meier and multivariate regression analyses. Results: Out of 86 identified patients, 58 (67.4%) had treatment failure of which 40 (46.5%) were due to progression. Median PFS and TTF were 12 and 8.5 months, respectively. A total of 57 (66.3%) and 42 (48.8%) patients experienced short-term and prolonged treatment benefit. Independent, significant predictors for PFS were progesterone receptor expression (HR: 0.88), multiple metastatic sites (HR: 2.56), and hepatic metastasis (HR: 2.01). Significant predictors for TTF were PR expression (HR: 0.86), multiple sites (HR: 3.29), adverse events (HR: 2.35), and diabetes (HR: 2.88). Aside from tumor biology and adverse events, treatment modifications like pausing and switching of CDKi were predictive for short-term (OR: 6.73) and prolonged (OR: 14.27) therapeutic benefit, respectively. Conclusions: These findings emphasize the importance of tailored treatment strategies, highlighting the role of PR expression, metastatic burden, and therapeutic adjustments in optimizing patient outcomes in real-world breast cancer management.

Purpose: In 2020, breast cancer still represents the most common type of cancer in women worldwide. Depending on the specific molecular subtype, clinical breast cancer management comprises surgery, radiotherapy, chemotherapy and targeted therapy. Furthermore, there are some therapeutic approaches from the field of complementary and alternative medicine. Current research focuses on the elucidation of new therapeutic targets for treatment development. Odorant substances affect apoptosis, proliferation and cell cycle in healthy and cancerous cells. Exact signalling pathways involved are not entirely clear. The present study aims to analyse their therapeutic potential in breast cancer. Methods: This study focuses on the effect of commonly used odorant substances (citral, citrathal R, cyclovertal, para-cymol, hexylacetat, herbavert, dihydromyrcerol and limonen) on the breast cancer cell lines MDA-MB-231, T47-D and BT474. Methodologically, this study applied cell culturing, MTT assay for detection of IC50 of the odorant substance, RNA purification followed by qRT-PCR, protein isolation and Western Blot, as well as immunocytochemistry. Further, this study investigates the role of transient receptor potential channel V1 (TRPV1), involved in the mechanisms of action for some odorant substances. Therefore, capsazepine, a TRPV1 antagonist, was used. Results: The odorant substances citral, citrathal R and cyclovertal have significant pro-apoptotic (p < 0.001), anti-proliferative (p < 0.001) and cell cycle-arresting effects measurable in RNA expression as well as in protein levels and immunocytochemical staining. The combination of citral and capsazepine no longer showed significant pro-apoptotic, antiproliferative, and cell cycle inhibitory effects compared to the compounds alone. This indicates that TRPV1 is necessary for the signal transduction of citral. Conclusion: This present study reveals three odorant substances with effects on cell viability, indicating their potential use in breast cancer therapy.

Molecular classification has reshaped risk stratification in endometrial cancer (EC), yet the relevance of tumor spread within molecular subgroups has not been reported so far. This multicenter retrospective study included 2056 EC patients treated between 1994 and 2018 across 11 European centers. All histopathological subtypes and FIGO stages were included. Tumors were classified into four molecular subgroups: POLE-mutated (POLEmut), mismatch repair deficient (MMRd), no specific molecular profile (NSMP), and TP53/p53 abnormal (p53abn). Clinical and pathological data were extracted from existing cohort databases. Patients were diagnosed with FIGO stage I (69 %), II (9 %), III (16 %), and IV (6 %), and classified into: POLEmut (8 %), MMRd (28 %), NSMP (44 %), and p53abn (21 %). The overall 5-year cancer-specific death (CSD) and recurrence rates were 16.5 % (95 % CI, 14.9 %-18.2 %) and 23.8 % (95 % CI, 22.0 %-25.7 %), respectively. In multivariable analysis cancer-specific survival (CSS) was independently associated with molecular subtype, FIGO stage, age, histopathological type, grade, lymphovascular space invasion, adjuvant therapy, residual tumor, and lymphadenectomy. FIGO stage was significantly associated with CSD also in within each molecular subgroup (p < 0.001). Patients with tumors confined to the uterus had the most favourable prognosis. Lymph node metastases significantly decreased CSS in POLEmut, MMRd, and p53abn groups. Within FIGO stage IV, molecular subtype was not significantly related to outcome. Surgical stage remains a strong prognostic factor across molecular subtypes and should be considered alongside molecular classification when tailoring adjuvant treatment in EC.

Background and Objectives: Cesarean scar and cervical pregnancies are rare forms of ectopic pregnancies, occurring in 1 in 2000 and 1 in 9000 pregnancies, respectively. Both entities are medically challenging due to their high morbidity and mortality potential. Materials and Methods: In this retrospective study, we analyzed all cesarean scar and cervical pregnancies from 2010 to 2019 in the Department of Gynecology and Obstetrics of the University Hospital Freiburg, treated with both intrachorial (using the ovum aspiration set) and systemic methotrexate application. Results: We identified seven patients with a cesarean scar and four patients with cervical pregnancies. At diagnosis, the median gestational age was 7 + 1 (range: 5 + 5–9 + 5) weeks and the mean value of ß-hCG was 43,536 (range: 5132–87842) mlU/mL. On average, one dose of intrachorial and two doses of systemic methotrexate were administered per patient. The efficacy rate was 72.7% with three patients (27.3%) needing an additional surgical or interventional procedure. The uterus was preserved in 100% of the patients. Out of the eight patients with follow-up data, five reported subsequent pregnancies (62.5%) that resulted in six live births. None had recurrent cesarean scars or cervical pregnancies. In the subgroup analyses, when comparing cesarean scar pregnancies to cervical pregnancies, patient characteristics, treatment modality, and the outcome did not differ significantly, except for parity (2 versus 0, p = 0.02) and the duration since the last pregnancy (3 vs. 0.75 years, p = 0.048). When comparing cases with successful and failed methotrexate-only treatments, the maternal age was significantly higher in the successful group (34 vs. 27 years, p = 0.02). Localization of the gestation, gestational and maternal age, ß-hCG, and history of preceding pregnancies were non-predictive for the efficacy of the treatment. Conclusions: The combined application of intrachorial and systemic methotrexate for the treatment of cesarean scar and cervical pregnancies has been proven effective, well-tolerated, organ- and fertility-conserving with a low complication rate.