Diagnosis and treatment monitoring in breast cancer: how liquid biopsy can support patient management

Imaging and tissue biopsies represent the current gold standard for breast cancer diagnosis and patient management. However, these practices are time-consuming, expensive and require invasive procedures. Moreover, tissue biopsies do not capture spatial and temporal tumor heterogeneity. Conversely, liquid biopsy, which includes circulating tumor cells, circulating free nucleic acids and extracellular vesicles, is minimally invasive, easy to perform and can be repeated during a patient's follow-up. Increasing evidence also suggests that liquid biopsy can be used to efficiently screen and diagnose tumors at an early stage, and to monitor changes in the tumor molecular profile. In the present review, clinical applications and prospects are discussed.

Early signatures of breast cancer up to seven years prior to clinical diagnosis in plasma cell-free DNA methylomes

Limited studies to date have investigated the detectability of cell-free DNA (cfDNA) markers in asymptomatic individuals prior to a cancer diagnosis. Here, we performed cfDNA methylation profiling in blood of individuals up to seven years prior to a breast cancer diagnosis in addition to matched cancer-free controls (n=150). We identified cfDNA differentially methylated signatures that discriminated cancer-free controls from pre-diagnosis breast cancer cases over five years prior to diagnosis and demonstrate that these markers were reflective of methylation profiles in breast cancer tissue. We report classification of a range of pre-diagnosis breast cancer cases detected at Stage I (area under the receiver operating characteristic curve (AUC) of 0.771), and in cases with a negative mammogram screening within a year of blood collection (AUC of 0.852). This study provides evidence that cfDNA methylation markers indicative of breast cancers can be detected in blood among asymptomatic individuals prior to clinical detection.

Breast cancer diagnosis using feature extraction and boosted C5.0 decision tree algorithm with penalty factor

<abstract><p>To overcome the two class imbalance problem among breast cancer diagnosis, a hybrid method by combining principal component analysis (PCA) and boosted C5.0 decision tree algorithm with penalty factor is proposed to address this issue. PCA is used to reduce the dimension of feature subset. The boosted C5.0 decision tree algorithm is utilized as an ensemble classifier for classification. Penalty factor is used to optimize the classification result. To demonstrate the efficiency of the proposed method, it is implemented on biased-representative breast cancer datasets from the University of California Irvine(UCI) machine learning repository. Given the experimental results and further analysis, our proposal is a promising method for breast cancer and can be used as an alternative method in class imbalance learning. Indeed, we observe that the feature extraction process has helped us improve diagnostic accuracy. We also demonstrate that the extracted features considering breast cancer issues are essential to high diagnostic accuracy.</p></abstract>

Trends in incidence, molecular diagnostics, and treatment of patients with breast cancer in Kazakhstan, 2014-2019

Relevance: Globocan reported 4,390 new breast cancer cases and 1,654 deaths from breast cancer in the Republic of Kazakhstan (RK) in 2020. Molecular diagnostics of breast cancer includes the determination of Hormone Receptor (HR), HER2, and Ki-67 status to detect patients with HR-positive tumors and administer effective treatment. Methods: This observational study included a retrospective analysis of incidence, molecular diagnostics, and treatment regimens in women with a confirmed breast cancer diagnosis aged 18 years old and older, registered in the RK Electronic Registry of Cancer Patients (ERCP) from 1 January 2014 till 31 December 2019. Results: In the study period (2014 to 2019), the number of breast cancer cases registered annually has doubled. The incidence increased by 46.9%. The share of locally advanced and advanced forms of breast cancer has decreased. The proportion of Luminal type A (HR+/HER2-) among newly diagnosed patients ranged from 17.9% to 30%. Chemotherapy and endocrine therapy with goserelin, buserelin, leuprorelin, and fulvestrant are standard first- and second-line treatments for HR+ breast cancer. Since fulvestrant indications have been expanded, more than 50% of patients with HR-positive advanced breast cancer receive fulvestrant as the first-line therapy. Conclusion: Breast cancer incidence growth and a decrease in the share of locally advanced and advanced breast cancer cases in the RK could be attributed to increased coverage of eligible women aged 40 to 70 with breast cancer mammographic screening. Although international guidelines support the administration of hormone therapy with or without targeted therapy in women with HR-positive, HER2-metastatic breast cancer, upfront use of chemotherapy remains common in the RK even in the absence of visceral crisis. The use of CDK4/6 inhibitor palbociclib in combination with hormone therapy has become routinely available since 2019.

BRCA2 Haploinsufficiency in Telomere Maintenance

Our previous studies showed an association between monoallelic BRCA2 germline mutations and dysfunctional telomeres in epithelial mammary cell lines and increased risk of breast cancer diagnosis for women with BRCA2 999del5 germline mutation and short telomeres in blood cells. In the current study, we analyzed telomere dysfunction in lymphoid cell lines from five BRCA2 999del5 mutation carriers and three Fanconi Anemia D1 patients by fluorescence in situ hybridization (FISH). Metaphase chromosomes were harvested from ten lymphoid cell lines of different BRCA2 genotype origin and analyzed for telomere loss (TL), multitelomeric signals (MTS), interstitial telomere signals (ITS) and extra chromosomal telomere signals (ECTS). TL, ITS and ECTS were separately found to be significantly increased gradually between the BRCA2+/+, BRCA2+/- and BRCA2-/- lymphoid cell lines. MTS were found to be significantly increased between the BRCA2+/+ and the BRCA2+/- heterozygous (p < 0.0001) and the BRCA2-/- lymphoid cell lines (p < 0.0001) but not between the BRCA2 mutated genotypes. Dysfunctional telomeres were found to be significantly increased in a stepwise manner between the BRCA2 genotypes indicating an effect of BRCA2 haploinsufficiency on telomere maintenance.

A Genetic-Fuzzy System Algorithm Method for the Breast Cancer Diagnosis Problem

Breast cancer is an important medical problem, especially for women, computer-aided medical diagnosis is very important in terms of prevention and early detection. This paper presents early detection of breast cancer using two methods, namely genetic algorithm and fuzzy inference system which will be used for early detection of breast cancer which will be used by doctors with computer assistance to obtain medical diagnosis of breast cancer in Indonesia. Our research shows that the diagnosis of breast cancer using these two methods has a high level of accuracy.