Early Diagnosis of Breast Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC5539491 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:MicroRNA (miRNA or miR) is stably present in plasma. It has been reported that miRNA could be used for detecting cancer. Circulating miRNAs are being increasingly recognized as powerful biomarkers in a number of different pathologies, including in breast cancer. The aim of the current study was to establish and validate miRNA sets that are useful for the early diagnosis of breast cancer. Specifically, the current study intended to determine whether miRNA biomarkers were tumor-specific and to statistically verify whether circulating miRNA analysis could be used for breast cancer diagnosis. In the present study, a total of nine candidate miRNA biomarkers were selected by examining reference miRNAs associated with the generation and progression of breast cancer to identify novel miRNAs that could be used to detect early breast cancer. A total of 226 plasma samples from patients with breast cancer were used. In addition, 146 plasma healthy samples were used as non-cancer controls. These samples were divided into training and validation cohorts. The training cohort was used to identify a combination of miRNA that could detect breast cancer. The validation cohort was used to validate this combination of miRNA. Total RNAs were isolated from collected samples. A total of 9 miRNAs were quantified using reverse-transcription quantitative PCR. A total of nine candidate miRNA expression levels were compared between patients with breast cancer and healthy controls. It was indicated that combinations of two or more of the nine miRNAs could detect breast cancer with higher accuracy than the use of a single biomarker. As a representative example, combinations of four miRNAs (miR-1246+miR-206+miR-24+miR-373) of the nine miRNAs had a sensitivity of 98%, a specificity of 96% and an accuracy of 97% for breast cancer detection in the validation cohort. The results of the present study suggest that multiple miRNAs could be used as potential biomarkers for early diagnosis of breast cancer. These biomarkers are expected to overcome limitations of mammography when used as an auxiliary diagnosis of mammography.
| S-EPMC7783718 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) play an important role in the development and progression of breast cancer (BC). The purpose of the present study was to identify plasma miRNAs enabling early diagnosis of BC.Materials and methodsExpression levels of seven plasma miRNAs (miR-23a-3p, miR-29b-2-5p, miR-130a-5p, miR-144-3p, miR-148a-3p, miR-152-3p, and miR-182-5p) in 106 patients with newly diagnosed BC and 96 healthy participants were analyzed by qRT-PCR. We also evaluated the relationship between the expression levels of these miRNAs and clinicopathological features of patients with BC.ResultsCompared with healthy controls, we found that miR-23a-3p (p = .025), miR-130a-5p (p = .006), miR-144-3p (p = .040), miR-148a-3p (p = .023), and miR-152-3p (p = .019) were downregulated in the plasma of patients with BC. MiR-130a-5p, miR-144-3p, and miR-152-3p were downexpressed in BC tissues as well as plasma. The expression of the miR-23a-3p, miR-144-3p, and miR-152-3p was related to ER positive and PR positive. Besides, miR-23a-3p, miR-144-3p, and miR-152-3p did show the significant difference in the staging compromised to the control, especially in stage I-II. Moreover, we also found that miR-144-3p and miR-148a-3p were associated with lymph node invasion.ConclusionsThe expression levels of the miR-23a-3p, miR-130a-5p, miR-144-3p, miR-148a-3p, and miR-152-3p were lower in patients with BC compared to healthy controls and were associated with ex hormone receptor, clinical stage, and lymph node metastasis, indicating the diagnostic potential of these miRNAs in BC.
| S-EPMC7216817 | biostudies-literature
Project description:BackgroundTwenty-eight states have passed breast density notification laws, which require physicians to inform women of a finding of dense breasts on mammography.ObjectiveTo evaluate changes in breast cancer stage at diagnosis after enactment of breast density notification legislation.DesignUsing a difference-in-differences analysis, we examined changes in stage at diagnosis among women with breast cancer in Connecticut, the first state to enact legislation, compared to changes among women in control states. We used data from the Surveillance, Epidemiology, and End Results Program (SEER) registry, 2005-2013.ParticipantsWomen ages 40-74 with breast cancer.InterventionBreast density notification legislation, enacted in Connecticut in October of 2009.Main measureBreast cancer stage at diagnosis.Key resultsOur study included 466,930 women, 25,592 of whom lived in Connecticut. Legislation was associated with a 1.38-percentage-point (95 % CI 0.12 to 2.63) increase in the proportion of women in Connecticut versus control states who had localized invasive cancer at the time of diagnosis, and a 1.12-percentage-point (95 % CI -2.21 to -0.08) decline in the proportion of women with ductal carcinoma in situ at diagnosis. Breast density notification legislation was not associated with a change in the proportion of women in Connecticut versus control states with regional-stage (-0.09 percentage points, 95 % CI -1.01 to 1.02) or metastatic disease (-0.24, 95 % CI -0.75 to 0.28). County-level analyses and analyses limited to women younger than 50 found no statistically significant associations.LimitationsSingle intervention state, limited follow-up, potential confounding from unobserved trends.ConclusionsBreast density notification legislation in Connecticut was associated with a small increase in the proportion of women diagnosed with localized invasive breast cancer in individual-level but not county-level analyses. Whether this finding reflects potentially beneficial early detection or potentially harmful overdiagnosis is not known. Legislation was not associated with changes in regional or metastatic disease.
| S-EPMC5442000 | biostudies-literature
Project description:Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4?×?10-5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2?×?10-23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.
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Project description:BackgroundAchieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results.MethodsWe examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer-specific mortality in a cohort of n = 12,590 stage I-III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0-9) years]. We divided follow-up into earlier (18-54 months) and later (>54 months) postdiagnosis periods.ResultsMean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (≥10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12-3.26) earlier and 1.60 (1.14-2.25) later in follow-up. Modest losses (>5%-<10%) were associated with worse survival earlier [1.39 (1.11-1.74)] but not later in follow-up [0.77 (0.54-1.11)]. Weight gain was not related to survival. Results were similar for breast cancer-specific death.ConclusionLarge postdiagnosis weight loss is associated with worse survival in both earlier and later postdiagnosis periods, independent of treatment and prognostic factors.ImpactWeight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. Cancer Epidemiol Biomarkers Prev; 26(1); 44-50. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".
| S-EPMC5224999 | biostudies-literature
Project description:PurposeMutations in hereditary breast cancer genes play an important role in the risk for cancer.MethodsCancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome.ResultsA total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001).ConclusionsHereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.
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Project description:BackgroundGermline BRCA1/2 pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of high-risk screening of the BRCA1/2 carrier population is limited.Patients and methodsRetrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of BRCA1/2 PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis.ResultsMedian follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma in situ. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had in situ disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34).ConclusionsHigh-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.
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Project description:Breast cancer affects 1 in 8 women globally, and is the leading cause of cancer-related deaths in female patients. The majority of breast cancer cases are of unknown cause; few are linked to genetic predisposition, and some arise sporadically. Finding the cause of these sporadic cases is an important area in cancer research. Investigations into the microbiome show links between microbiome dysbiosis and breast cancer, with possible mechanisms in the association of the microbiome and breast cancer, including estrogen metabolism and the 'oestrobolome,' immune regulation, propensity for obesity, and the regulation of the tumor microenvironment. This paper reviews the literature and discusses the potential implications of links between the microbiome and breast cancer, and concludes that the microbiome may have significant applications as a biomarker for breast cancer diagnosis, prognosis, and management. Further investigation is crucial, since modification of the microbiome can, at the most basic level, be achieved via dietary modification.
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Project description: Not available
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Project description:Breast cancer is the most common type of cancer among women and despite recent advances in the medical field, there are still some inherent limitations in the currently used screening techniques. The radiological interpretation of screening X-ray mammograms often leads to over-diagnosis and, as a consequence, to unnecessary traumatic and painful biopsies. Here we propose a computer-aided multifractal analysis of dynamic infrared (IR) imaging as an efficient method for identifying women with risk of breast cancer. Using a wavelet-based multi-scale method to analyze the temporal fluctuations of breast skin temperature collected from a panel of patients with diagnosed breast cancer and some female volunteers with healthy breasts, we show that the multifractal complexity of temperature fluctuations observed in healthy breasts is lost in mammary glands with malignant tumor. Besides potential clinical impact, these results open new perspectives in the investigation of physiological changes that may precede anatomical alterations in breast cancer development.
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