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UNASSIGNED: Breast cancer causes the most cancer-related death in women and is the costliest cancer in the US regarding medical service and prescription drug expenses. Breast cancer screening is recommended by health authorities in the US, but current screening efforts are often compromised by high false positive rates. Liquid biopsy based on circulating tumor DNA (ctDNA) has emerged as a potential approach to screen for cancer. However, the detection of breast cancer, particularly in early stages, is challenging due to the low amount of ctDNA and heterogeneity of molecular subtypes.
UNASSIGNED: Here, we employed a multimodal approach, namely Screen for the Presence of Tumor by DNA Methylation and Size (SPOT-MAS), to simultaneously analyze multiple signatures of cell free DNA (cfDNA) in plasma samples of 239 nonmetastatic breast cancer patients and 278 healthy subjects.
UNASSIGNED: We identified distinct profiles of genome-wide methylation changes (GWM), copy number alterations (CNA), and 4-nucleotide oligomer (4-mer) end motifs (EM) in cfDNA of breast cancer patients. We further used all three signatures to construct a multi-featured machine learning model and showed that the combination model outperformed base models built from individual features, achieving an AUC of 0.91 (95% CI: 0.87-0.95), a sensitivity of 65% at 96% specificity.
UNASSIGNED: Our findings showed that a multimodal liquid biopsy assay based on analysis of cfDNA methylation, CNA and EM could enhance the accuracy for the detection of early- stage breast cancer.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Breast cancer is the most common cancer in women all over the world, also in Vietnam. In recent years, the incidence of breast cancer has been increasing in Vietnam, and most cases are diagnosed at late stages, making treatment more difficult. More and better early detection could help more women to survive. The aim of this study was to identify the current knowledge, attitude and practice about early detection of breast cancer as well as potential predictors of breast cancer screening among women aged 20 to 49 year in a mountainous commune in Thanh Hoa Province, Vietnam, in a largely ethnic Muong population. Women aged 20 to 49 years were selected by systematic random sampling to participate in a cross sectional study in October 2017. They were interviewed with a closed questionnaire about their knowledge of breast cancer, its risk factors, and warning signs. A checklist for performance of breast self-examination was also applied. Three hundred six women agreed to participate in the study. More than half had a low level of knowledge, and were weak in attitude and practice about breast self-examination, clinical breast examination, breast ultrasound, and mamography. Among women who had practiced at least 1 screening method, 17.0% mentioned clinical breast examination, and only 13.8% reported practicing breast self-examination. Factors associated with practice included knowledge about breast cancer early detection (BCED), ethnicity, income, the BCED information approach, and the BCED screening programs approach. The finding of a very low proportion of women in the mountainous setting with good awareness and practice on early detection of breast cancer is important evidence to inform the BCED intervention program developers about where and how to target which information, especially to reach more ethnic minority women.

BACKGROUND: Information on pathways of women seeking diagnostic services due to breast- related symptoms can help highlight challenges related to the healthcare system in improving early diagnosis of breast cancer.
METHODS: We retrospectively analysed the entire patient pathway, from first symptom recognition via initial healthcare visit up to final diagnosis at the pathology service in Mali. Data from questionnaire-based structured patient interviews (n = 124) were used to calculate time to first healthcare visit (median 91 days) and consecutive time to diagnosis (median 21 days) and to extract information on type of initially visited healthcare facility (community healthcare centre, referral hospital, tertiary hospital, private clinic). Median time to first healthcare visit and time to diagnosis and type of initially-visited healthcare facility were cross-tabulated with patient characteristics. An additional survey among (n = 30) medical doctors in the community healthcare centres and referral hospitals in Bamako was conducted to understand current knowledge and referral practice with respect to female patients with breast-related symptoms.
RESULTS: Patients who initially visited private clinics had the shortest time to first healthcare visit (median 44 days), but the longest time to diagnosis (median 170 days). Patients visiting community healthcare centres and referral hospitals took longest for a first healthcare visit (median 153 and 206 days, respectively), but the time to diagnosis was shorter (median 95 and 7 days, respectively). The majority of patients (45%) initially visited a tertiary hospital; these patients had shortest total time to diagnosis (median 56 days health seeking and 8 days diagnostic time), but did not follow the recommended pathway for patients in the pyramidal healthcare system in Mali. The doctors\' survey showed lower breast cancer knowledge in the community healthcare centres than in the referral hospitals. However, most doctors felt able to recognise suspected cases of cancer and referred patients directly to a hospital.
CONCLUSIONS: The role of different healthcare facilities in ensuring triage of patients with breast-related symptoms needs to be defined before any early detection initiatives are implemented. Especially at the entry level of the healthcare system, the access and quality of health services need to be strengthened.

Serum circulating microRNAs (c-miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one-step branched rolling circle amplification (BRCA) method to measure serum c-miRNAs levels for early diagnosis of breast cancer. Four c-miRNAs, c-miRNA16 (c-miR-16), c-miRNA21 (c-miR-21), c-miRNA155 (c-miR-155), and c-miRNA195 (c-miR-195) were isolated from the serum of 49 breast cancer patients and 19 healthy controls. Among them, 45 breast cancer patients and 15 healthy controls were analyzed using one-step BRCA, 4 breast cancer patients and 4 healthy controls were analyzed by quantitative real-time PCR assay [corrected]. The serum levels of c-miR16, c-miR21, c-miR155, and c-miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER-2 over-expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c-miR16, c-miR21, c-miR155, and c-miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c-miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real-time PCR (qRT-PCR) method show that the serum levels of c-miR16, c-miR21, c-miR155, and c-miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.