Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases.

BACKGROUND: As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer? MATERIAL AND METHODS: We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated. RESULTS: Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy "hormonal treatment". CONCLUSIONS: Support of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.

ABRAXAS1 orchestrates BRCA1 activities to counter genome destabilizing repair pathways-lessons from breast cancer patients.

It has been well-established that mutations in BRCA1 and BRCA2, compromising functions in DNA double-strand break repair (DSBR), confer hereditary breast and ovarian cancer risk. Importantly, mutations in these genes explain only a minor fraction of the hereditary risk and of the subset of DSBR deficient tumors. Our screening efforts identified two truncating germline mutations in the gene encoding the BRCA1 complex partner ABRAXAS1 in German early-onset breast cancer patients. To unravel the molecular mechanisms triggering carcinogenesis in these carriers of heterozygous mutations, we examined DSBR functions in patient-derived lymphoblastoid cells (LCLs) and in genetically manipulated mammary epithelial cells. By use of these strategies we were able to demonstrate that these truncating ABRAXAS1 mutations exerted dominant effects on BRCA1 functions. Interestingly, we did not observe haploinsufficiency regarding homologous recombination (HR) proficiency (reporter assay, RAD51-foci, PARP-inhibitor sensitivity) in mutation carriers. However, the balance was shifted to use of mutagenic DSBR-pathways. The dominant effect of truncated ABRAXAS1 devoid of the C-terminal BRCA1 binding site can be explained by retention of the N-terminal interaction sites for other BRCA1-A complex partners like RAP80. In this case BRCA1 was channeled from the BRCA1-A to the BRCA1-C complex, which induced single-strand annealing (SSA). Further truncation, additionally deleting the coiled-coil region of ABRAXAS1, unleashed excessive DNA damage responses (DDRs) de-repressing multiple DSBR-pathways including SSA and non-homologous end-joining (NHEJ). Our data reveal de-repression of low-fidelity repair activities as a common feature of cells from patients with heterozygous mutations in genes encoding BRCA1 and its complex partners.

The Transobturator Tape Versus Retropubic Tension-Free Vaginal Tape in the Treatment of Comorbid and Elderly Women With Stress Urinary Incontinence: A Retrospective Analysis of Over 800 Women.

Background and objective The first-line surgical treatment for female stress urinary incontinence (SUI) involves midurethral slings (MUS), including the transobturator tape (TOT) and the retropubic tension-free vaginal tape (TVT). However, whether offering these procedures to older and comorbid women could lead to increased complications is a question that needs to be seriously addressed. In this retrospective cohort study, we aimed to compare the two procedures and evaluate the impact of age, BMI, and comorbidities on complications. Materials and methods A total of 873 procedures (306 TVTs/567 TOTs) performed between 2007 and 2017 were compared and correlated with regard to age, BMI, and comorbidities. Intraoperative complications included bleeding >50 ml, bladder injury, and anesthesia-associated complications. Postoperative complications included post-void residual volume, pain, hematoma, lower urinary tract infection, revision for loosening tape, and bladder infections. The comorbidities were evaluated based on the American Society of Anesthesiologists (ASA) and Charlson scores. Results A total of 873 MUS were conducted during the study period: 306 TVTs and 567 TOTs. Groupwise comparison between these procedures showed that women in the TOT group were older (p<0.001) with a higher BMI (p<0.001) and a higher ASA score (p<0.001) compared to the TVT group. Nevertheless, significantly more intraoperative complications, especially bladder injuries, were recorded in the TVT group. Postoperative complications occurred in 19.4% of the entire cohort, especially increased post-void residual volume. Postoperative hematoma and tape loosening were significantly more frequent in the TOT group. Age, BMI, and comorbidities showed no significant impact on intraoperative complications; however, the TOT procedure was associated with significantly fewer intraoperative complications [p=0.001, odds ratio (OR): 0.281]. Conclusions Overall, both procedures were associated with a low number of perioperative complications. The TOT technique had a lower incidence of intraoperative complications. It must be highlighted that age and comorbidities had no influence on either the intra- or postoperative complication rates. Hence, we recommend that TOT is employed to treat SUI in older, more obese, and comorbid women.

Circulating Tumor Cells in Breast Cancer Patients: A Balancing Act between Stemness, EMT Features and DNA Damage Responses.

Circulating tumor cells (CTCs) traverse vessels to travel from the primary tumor to distant organs where they adhere, transmigrate, and seed metastases. To cope with these challenges, CTCs have reached maximal flexibility to change their differentiation status, morphology, migratory capacity, and their responses to genotoxic stress caused by metabolic changes, hormones, the inflammatory environment, or cytostatic treatment. A significant percentage of breast cancer cells are defective in homologous recombination repair and other mechanisms that protect the integrity of the replication fork. To prevent cell death caused by broken forks, alternative, mutagenic repair, and bypass pathways are engaged but these increase genomic instability. CTCs, arising from such breast tumors, are endowed with an even larger toolbox of escape mechanisms that can be switched on and off at different stages during their journey according to the stress stimulus. Accumulating evidence suggests that DNA damage responses, DNA repair, and replication are integral parts of a regulatory network orchestrating the plasticity of stemness features and transitions between epithelial and mesenchymal states in CTCs. This review summarizes the published information on these regulatory circuits of relevance for the design of biomarkers reflecting CTC functions in real-time to monitor therapeutic responses and detect evolving chemoresistance mechanisms.