Breast cancer (BC) significantly impacts the quality of life (QoL) of affected individuals. This study, conducted at Colțea Clinical Hospital, Bucharest, aimed to assess the impact of organ failures and metastases on QoL in breast cancer patients using EORTC QLQ-C30 and EORTC QLQ-BR45 questionnaires and the survival rate to understand the clinical journey and the quality of life status in breast cancer patients. From January 2019 to October 2022, a prospective, observational study surveyed 874 patients, revealing 201 fatalities, 66 refusals, and 607 eligible participants. Results indicated statistically significant differences in various QoL aspects for patients experiencing heart failure, including physical functioning, pain, insomnia, global health status, and overall summary score. Kidney failure exhibited significance in physical functioning for QLQ-C30 and body image, sexual functioning, and endocrine sexual symptoms for QLQ-BR45. Respiratory failure demonstrated significant differences across multiple QoL domains. Patients with bone metastases reported lower physical functioning (p = 0.006) and increased pain (p = 0.002). This study has revealed an overall 5-year life expectancy of 68.8%, with survival rates of 93.8% for Stage I, 86.3% for Stage II, and 77.2% for Stage III breast cancer. Metastatic cancer patients have shown a 35.6% survival rate over 45 months, with a median survival duration of 36 months. A significant limitation of our study was the administration of the questionnaire only once, preventing us from quantifying the impact of specific treatment types on quality of life. This study emphasizes the necessity of using standardized QoL assessments in clinical practice from the initial presentation to ongoing follow-up.

Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA).
Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes.
A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited-only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster.
The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for therapy management in oncology. We aimed to establish a multimodal liquid biopsy strategy that is usable with minimized blood volume to deconvolute the genomic complexity of metastatic breast cancer. CTCs were isolated from 10ml blood of 18 hormone receptor-positive and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer patients. cfDNA was isolated from plasma generated after CTC depletion and targeted sequencing analyses were conducted. PIK3CA and ESR1 variants were less common in CTC gDNA, while ERBB2 variants were only detected in CTC gDNA. A total of 62% of all cfDNA variants were recovered in the matched CTC gDNA, while 72% of all variants were unique in either cfDNA (14 variants) or CTC gDNA (104 variants). The percentage of patients with no detectable cfDNA variants or CTC gDNA variants was 17%/11%, but a combined analysis identified variants in 94% of all patients. In univariate and multivariate regression models, ESR1 variants in cfDNA and CTC gDNA correlated significantly with survival. We suggest a coordinated analysis of both fractions in order to provide a comprehensive genomic footprint that may contribute to identifying the most suitable therapy for each individual.