Abstract:KRAS/BRAF mutations are with very few exceptions constrained to patients with histopathologic type 1 tumors, whereas p53 overexpression is very frequent in type 2 tumors. KRAS/BRAF mutations had independent prognostic importance. The classification presented here should have a major therapeutic implication and serve as a hallmark of future clinical trials.
“…The analyses were performed by an in-house developed assay, which has been used, validated and previously described in detail (14,16,20). The PCR-fragment used in the present study was short (only 102 bp), increasing the detection rate of even small fragments of cfDNA in the plasma.…”
Section: Discussionmentioning
confidence: 99%
“…The KRAS mutations were also analysed by in-house qPCR assays as previously described in detail (14,20). In brief, six mutations of codon 12 and one in codon 13 of the KRASgene were identified by an ARMS-qPCR method.…”
Section: Plasma Analyses Of Cfdna and Krasmentioning
Abstract. Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in the Western world and is associated with a poor prognosis. Biomarkers predicting prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA) may be a feasible option. Genetic mutations can be analysed in plasma and may increase the scientific use of such measurements. In the present study, we investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during the treatment of patients with advanced NSCLC; and ii) the prognostic value of baseline cfDNA and pmKRAS. Sixty-nine patients were included in a prospective biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first-line treatment, no previous cancer within the five years prior to this study. Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA and KRAS mutations in plasma were performed using an in-house qPCR assay. Evaluation of the treatment effect and status at follow-up was performed according to RECIST 1.1. The median levels of cfDNA were significantly higher at progression (9,250 alleles/ml) than at baseline (5,450 alleles/ml). Overall survival and progressionfree survival were both significantly shorter in patients with high levels of cfDNA (above the 75th percentile) compared to lower levels. Only few patients harboured KRAS mutations in plasma. Two patients had no KRAS mutations in plasma at baseline, but mutations appeared in the subsequent blood samples. High baseline levels of cfDNA indicate a poor prognosis. The level changes during the treatment course with a significant increase at progression, suggesting a possible predictive value of cfDNA. The plasma KRAS status may change during treatment with potential implications for treatment selection.
“…The analyses were performed by an in-house developed assay, which has been used, validated and previously described in detail (14,16,20). The PCR-fragment used in the present study was short (only 102 bp), increasing the detection rate of even small fragments of cfDNA in the plasma.…”
Section: Discussionmentioning
confidence: 99%
“…The KRAS mutations were also analysed by in-house qPCR assays as previously described in detail (14,20). In brief, six mutations of codon 12 and one in codon 13 of the KRASgene were identified by an ARMS-qPCR method.…”
Section: Plasma Analyses Of Cfdna and Krasmentioning
Abstract. Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in the Western world and is associated with a poor prognosis. Biomarkers predicting prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA) may be a feasible option. Genetic mutations can be analysed in plasma and may increase the scientific use of such measurements. In the present study, we investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during the treatment of patients with advanced NSCLC; and ii) the prognostic value of baseline cfDNA and pmKRAS. Sixty-nine patients were included in a prospective biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first-line treatment, no previous cancer within the five years prior to this study. Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA and KRAS mutations in plasma were performed using an in-house qPCR assay. Evaluation of the treatment effect and status at follow-up was performed according to RECIST 1.1. The median levels of cfDNA were significantly higher at progression (9,250 alleles/ml) than at baseline (5,450 alleles/ml). Overall survival and progressionfree survival were both significantly shorter in patients with high levels of cfDNA (above the 75th percentile) compared to lower levels. Only few patients harboured KRAS mutations in plasma. Two patients had no KRAS mutations in plasma at baseline, but mutations appeared in the subsequent blood samples. High baseline levels of cfDNA indicate a poor prognosis. The level changes during the treatment course with a significant increase at progression, suggesting a possible predictive value of cfDNA. The plasma KRAS status may change during treatment with potential implications for treatment selection.
“…BRAF mutation is mainly found in ovarian serous adenoma, SBTs, invasive MPSC, and mucinous carcinomas. 4,17,18,45,46 It is generally believed that adenoma progresses to SBT and then to LGSC. The pathologic difference between SBTs and LGSC is the destructive stromal invasion in LGSC.…”
Section: Role Of Braf Mutation In the Pathogenesis Of Ovarian Cancermentioning
confidence: 99%
“…11 BRAF mutation is also rare in primary clear cell ovarian carcinoma (1%), 12,13 mucinous borderline tumors (2%), [13][14][15] and endometrioid carcinoma (3%), 16 but is relatively more frequent in mucinous carcinoma 4,17 and serous adenoma.…”
mentioning
confidence: 99%
“…4,13,15,17,46,[60][61][62] Unlike the serous adenoma with similar BRAF mutations as SBTs, none of the mucinous adenomas (n=40) had a detectable BRAF mutation. 15 Since it is believed that mucinous adenoma can progress as mucinous borderline tumor and then 58 BRAF V600E mutations were identified in 35% of 75 patients with ovarian SBTs or LGSC, and the BRAF V600E mutation in these tumors was associated with early-stage disease and improved prognosis.…”
BRAF mutations are rare in ovarian cancer and mainly occur in indolent serous borderline tumors (SBTs), also known as serous tumors of low malignant potential or atypical proliferative serous tumors. The reported percentage of BRAF mutations in SBTs varies from 23% to 71%. Although a high percentage of stage II-IV SBTs with noninvasive implants have progressed to invasive low-grade serous carcinomas when patients were observed for 5 years or longer, BRAF mutations are rare in low-grade serous carcinomas as well as in invasive implants associated with SBTs. BRAF mutations in SBTs may prevent SBTs from progressing to invasive carcinomas. On the other hand, the reported percentage of BRAF mutations in mucinous carcinoma (20%) is much higher than that of mucinous borderline tumor (5%). Further investigation of the role of BRAF mutations in SBTs and mucinous tumor will shed light on the molecular mechanism underlying the role of BRAF mutations in tumor progression in different cellular context and the clinical utility of BRAF mutations in SBTs as a biomarker of favorable prognosis.
For women who are candidates for menopausal hormone therapy (MHT), estrogen can provide relief from symptomatic menopause, decrease rates of chronic illnesses, and improve health‐related quality of life. However, confusion surrounds the evidence regarding the impact of exogenous estrogen and progesterone on the breast and ovary. Available data regarding the risks of MHT (estrogen and/or progestin) related to the development of breast and ovarian cancer are often inconsistent or incomplete. Modern molecular and genetic techniques have improved our understanding of the heterogeneity of breast and ovarian cancer. This enhanced understanding of the disease has impacted our understanding of carcinogenesis. Treatment options have evolved to be more targeted toward hormonal therapy for certain subtypes of disease, whereas cytotoxic chemotherapy remains the standard for other histological and molecular subtypes. The role of MHT in the breast and ovarian cancer survivor, as well as women who are at high risk for the development of hereditary breast and ovarian cancer, remains controversial despite evidence that this treatment can improve quality of life and survival outcomes. Through this article, we examine the evidence for and against the use of MHT with a focus on women who have or are at high risk for breast and ovarian cancer.
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