Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and <i>TP53</i> Mutation Status in Triple-Negative Cases

This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions

Delays in diagnosis and treatment of breast cancer: a multinational analysis

BACKGROUND: Reducing treatment delay improves outcomes in breast cancer. The aim of this study was to determine factors influencing patient- and system-related delays in commencing breast cancer treatment in different countries. METHODS: A total of 6588 female breast cancer patients from 12 countries were surveyed. Total delay time was determined as the sum of the patient-related delay time (time between onset of the first symptoms and the first medical visit) and system-related delay time (time between the first medical visit and the start of therapy). RESULTS: The average patient-related delay time and total delay time were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively. Longer patient-related delay times were associated with distrust and disregard, and shorter patient-related delay times were associated with fear of breast cancer, practicing self-examination, higher education level, being employed, having support from friends and family and living in big cities. The average system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made by an oncologist versus another physician, higher education level, older age, family history of female cancers and having a breast lump as the first cancer sign were associated with shorter system-related delay times. Longer patient-related delay times and higher levels of distrust and disregard were predictors of longer system-related delay times. CONCLUSIONS: The delay in diagnosis and treatment of breast cancer remains a serious problem. Several psychological and behavioural patient attributes strongly determine both patient-related delay time and system-related delay time, but their strength is different in particular countries

Delays in diagnosis and treatment of breast cancer: a multinational analysis

Background: Reducing treatment delay improves outcomes in breast cancer. The aim of this study was to determine factors influencing patient-and system-related delays in commencing breast cancer treatment in different countries. Methods: A total of 6588 female breast cancer patients from 12 countries were surveyed. Total delay time was determined as the sum of the patient-related delay time (time between onset of the first symptoms and the first medical visit) and system-related delay time (time between the first medical visit and the start of therapy). Results: The average patient-related delay time and total delay time were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively. Longer patient-related delay times were associated with distrust and disregard, and shorter patient-related delay times were associated with fear of breast cancer, practicing self-examination, higher education level, being employed, having support from friends and family and living in big cities. The average system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made by an oncologist versus another physician, higher education level, older age, family history of female cancers and having a breast lump as the first cancer sign were associated with shorter system-related delay times. Longer patient-related delay times and higher levels of distrust and disregard were predictors of longer system-related delay times. Conclusions: The delay in diagnosis and treatment of breast cancer remains a serious problem. Several psychological and behavioural patient attributes strongly determine both patient-related delay time and system-related delay time, but their strength is different in particular countries