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The objective of the present study was to evaluate the epigenetic changes occurring in early stages of breast cancer. The present study investigated the methylation profile of the ATM, p14 ARF and p16 INK4a promoters in total blood and plasma cell-free DNA (cfDNA) from women with impalpable breast lesions compared with in total blood of a control cohort of women without breast lesions. The samples were evaluated using the methylation-specific PCR method. The Fisher's exact test was used to evaluate statistical significance between the methylation and clinical variables. A total of 111 women were evaluated, including 56 women with impalpable breast cancer (39/56 also had paired plasma cfDNA) and 55 women in the control cohort (55 blood DNA). For blood DNA from women with malignant impalpable breast lesions, p16 INK4a exhibited the greatest percentage of methylation (48%), followed by ATM (37.5%) and p14 ARF (27%) promoters, regardless of age variation. For plasma cfDNA, the methylation rates for ATM, p14 ARF and p16 INK4a were 26, 26 and 10%, respectively. The methylation rates for the blood DNA of controls were the lowest for ATM (9%), p14 ARF (7%) and p16 INK4a (7%). The women with impalpable breast lesions (benign and malignant lesions) exhibited the highest methylation rate, regardless of age, compared with the paired plasma cfDNA and controls. This epigenetic change was statistically significant for the promoters of ATM (P=0.009) and p16 INK4a (P=0.001) (impalpable breast lesions vs. control). The present study demonstrated that epigenetic changes occurring in the ATM and CDKN2A genes detectable in liquid biopsy were associated with the development of impalpable breast lesions.

The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies and breast cancer cell lines with blood samples from patients with conditions other than cancer. A total of 859 samples were analyzed at the discovery stage, consisting of 417 mammary tumors, 41 breast lines, and 401 control samples. To confirm this discovery, external datasets of eight types of tumors were used, and experimental validation studies (NanoString n-counter gene expression assay) were performed, totaling 5028 samples analyzed. In these analyses, the 80 biomarkers showed higher expression in all solid tumors analyzed relative to healthy blood samples. Experimental validation studies using NanoString assay confirmed the results were not dependent of the gene expression platform. A panel of 80 RNA biomarkers was described here, with the potential to detect solid tumor cells present in the blood of multiple tumor types.

Background:Low levels of vitamin D have been described as a risk factor for the development of breast cancer. The aim of this study was to evaluate the serum levels of vitamin D (25OHD) in patients with impalpable breast lesions comparing with a control group.Methods:Vitamin D quantification (25OHD) was assessed in the plasma of 65 patients with impalpable breast lesions and from 20 health controls using a chemiluminescent microparticle immunoassay. Pearson’s chi-square test and nonparametric t-Student were used to evaluate statistical significance between the clinical variables and the means of quantification of vitamin D. The receiver operating characteristic (ROC) curve was used to evaluate the correlation between age and vitamin sufficiency for the cases and the controls.Results:The prevalence of vitamin D deficiency and/or insufficiency in women with malignant lesions was 84% and 60% for the control group. Using the chi-square or Fisher’s exact test, the relationship between vitamin D levels and age presented significant association only for the control group (P=0.002). Using ROC curve, the plot area (0.778) for the control group defined a cut-off value of 45 years to age, with specificity and sensitivity of 60% and 50%, respectively. Thus, the odds ratio for vitamin D insufficiency in women over 45 years was 1.37 (P=0.011). For the case group, clinical characteristics, histological grade, and lymph node involvement did not show any significant association.Conclusion:The prevalence of vitamin D deficiency/insufficiency is high in women with impalpable breast lesions, as well as in the control group, even in a tropical city. According to the results the age advancement may be involved with the decrease in vitamin D levels in plasma, but there was no statistical association between low levels of Vitamin D and breast cancer.

In early 2020, the book "Breast cancer: Global Quality Care" was published by Oxford University Press. In the year since then, publications, interviews (by ecancer), presentations, webinars, and virtual congress have been organized to disseminate further the main message of the project: "A call for Fairer Breast Cancer Care for all Women in a Globalized World." Special attention is paid to increasing the "value-based healthcare" putting the patient in the center of the care pathway and sharing information on high-quality integrated breast cancer care. Specific recommendations are made considering the local resource facilities. The multidisciplinary breast conference is considered "the jewel in the crown" of the integrated practice unit, connecting multiple specializations and functions concerned with patients with breast cancer. Management and coordination of medical expertise, facilities, and their interfaces are highly recommended. The participation of two world-leading cancer research programs, the CONCORD program and Breast Health Global Initiative, in this project has been particularly important. The project is continuously under review with feedback from the faculty. The future plan is to arrive at an openaccess publication that is freely available to all interested people. This project is designed to help ease the burden and suffering of women with breast cancer across the globe.

Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and Methods:The Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022.Results: Twenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). Conclusion:This survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and

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