Mutational status and thromboembolic risk in lung, gastrointestinal and breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23147-e23147
Author(s):  
Marco Platania ◽  
Federico Nichetti ◽  
Filippo G. De Braud
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Molecular Profile ◽  
Breast Cancer Patients ◽  
Vein Thrombosis ◽  
Mutational Status ◽  
Cancer Associated Thrombosis ◽  
Low Prevalence

e23147 Background: Cancer-Associated Thrombosis (CAT) is one of the most threatening complications of cancer. Recent evidences suggested a link between the molecular profile of solid tumors and the incidence of CAT. The aim of this study was to explore the relationship between the mutational status of breast, lung and gastrointestinal cancer patients and the risk of CAT. Methods: We retrospectively evaluated the molecular profile, analysed as per clinical practice, of all consecutive patients hospitalized at the National Cancer Institute’s Department in Milan from October 2017 to November 2018. Patients with previous thromboembolic events and patients under anticoagulant therapy at cancer diagnosis were excluded. Due to death as competing risk, the Fine and Gray proportional regression model was used to detect statistical association and estimate relative risk. Results: The resulting cohort consisted of 484 patients, of whom 47% had gastrointestinal cancers, 18% had lung cancer and 15% had breast cancer. Molecular investigations were available for 375 (77%) patients; in particular, a 50-gene Next Generation Sequencing (NGS) panel was performed on 148 (31%) patients. After a median follow up of 17 months, 118 patients (24%) exhibited clinical manifestations of thrombosis (i.e. deep vein thrombosis, pulmonary thromboembolism, splanchnic thrombosis, disseminated intravascular coagulation, arterial thrombosis) and 117 (24%) patients deceased without thrombotic events. A statistically significant association was observed between incidence of CAT and presence of TP53 (HR 0.50, p = 0.04), c-KIT (HR 4.30, p = 0.041), and SMAD4 (HR 3.19, p = 0.029) mutations. No significant association was detected for KRAS and MET gene mutations, even if HRs were >2. Conclusions: In this study, the mutational status of TP53, SMAD4 and c-KIT genes was statistically associated to the risk of thrombosis. Due to methodological limits and low prevalence of mutations, large prospective studies are warranted, with the aim of better defining the role of oncogenes in CAT risk.

scholarly journals Low Prevalence of CHEK2 Gene Mutations in Multiethnic Cohorts of Breast Cancer Patients in Malaysia

PLoS ONE ◽  
2015 ◽  
Vol 10 (1) ◽  
pp. e0117104 ◽  
Author(s):  
Suriati Mohamad ◽  
Nurismah Md Isa ◽  
Rohaizak Muhammad ◽  
Nor Aina Emran ◽  
Nor Mayah Kitan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Breast Cancer Patients ◽  
Chek2 Gene ◽  
Low Prevalence

BRCA gene mutations in Slovenian male breast cancer patients

2007 ◽  
Vol 4 (03) ◽  
Author(s):  
N Besic ◽  
B Cernivc ◽  
J De Greve ◽  
K Lokar ◽  
M Krajc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Gene Mutations ◽  
Male Breast ◽  
Breast Cancer Patients ◽  
Brca Gene

scholarly journals Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3366
Author(s):  
Anna-Sophie Liegmann ◽  
Kerstin Heselmeyer-Haddad ◽  
Annette Lischka ◽  
Daniela Hirsch ◽  
Wei-Dong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Genome Instability ◽  
Single Cells ◽  
Gene Mutations ◽  
Intratumor Heterogeneity ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

Clinical significance of estrogen receptor 1 gene mutations in hormonal resistant breast cancer patients

Gene Reports ◽  
2021 ◽  
pp. 101261
Author(s):  
Reham A. Aboelwafa ◽  
Nermine H. Zakaria ◽  
Neamat Hagazy ◽  
Inas I. Zaki ◽  
Aya S. Rady ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Gene Mutations ◽  
Breast Cancer Patients ◽  
Estrogen Receptor 1

scholarly journals Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients

2014 ◽  
Vol 9 (4) ◽  
pp. 749-757 ◽  
Author(s):  
Marta Pestrin ◽  
Francesca Salvianti ◽  
Francesca Galardi ◽  
Francesca De Luca ◽  
Natalie Turner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Single Cell Level ◽  
Breast Cancer Patients ◽  
Cell Level ◽  
Mutational Status

Prospective synoptic template recording to assess for compliance of care with NCCN guidelines for breast cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 197-197
Author(s):  
Titilayo Adegboyega ◽  
Jeffrey Landercasper ◽  
Jared Linebarger ◽  
Jeanne Johnson ◽  
Leah L. Dietrich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Recognition ◽  
Performance Comparison ◽  
Molecular Profile ◽  
Breast Cancer Patients ◽  
Preoperative Testing ◽  
Nccn Guidelines ◽  
Real Time Analysis ◽  
Cancer Network

197 Background: There is a wide variation of compliance with National Comprehensive Cancer Network (NCCN) guidelines for diagnosis and treatment. Overutilization of preoperative testing and underutilization of adjuvant treatments have been documented. The former is associated with higher costs of care; the latter with poor patient outcomes. Prior reports of adherence to NCCN Guidelines contain methodological limitations due to lack of contemporary review and incomplete listing of reasons for non-compliance. This limits the “real time” analysis of breast cancer quality and delays action plans to address quality and cost issues of care. Methods: NCCN Guideline compliance was recorded prospectively by use of electronic synoptic templates for all newly diagnosed breast cancer patients treated at a single institution between January 2010 and December 2011. A retrospective review of the synoptic templates was then conducted. Accuracy of the synoptic auditing method was assessed as well as NCCN compliance and reasons for non-compliance. Results: A total of 312 new breast cancer patients who underwent surgery as initial treatment were identified. Compliance with NCCN Guidelines for preoperative testing, breast surgery and lymph node surgery was 98% (306/312), 99.7% (311/312) and 93% (290/312) respectively. Reasons for non-compliance include patient refusal, comorbidities, advanced age and overutilization of systemic imaging. There was 100% compliance to College of American Pathologist (CAP) molecular profile documentation for all breast cancer cases. There were two discrepancies noted between the prospective template reporting and medical record review. The average time needed to populate data into synoptic templates was less than 2 minutes per patient. Conclusions: Prospective auditing of adherence to NCCN Guidelines with electronic synoptic templates is accurate and time efficient. High compliance rates with NCCN Guidelines were demonstrated. Electronic synoptic NCCN templates potentially facilitate early recognition of quality gaps in compliance and provide a framework for peer performance comparison.

Diagnostic yield and clinical utility of germline genetic testing following somatic testing in breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1092-1092
Author(s):  
Stephen E Lincoln ◽  
Kingshuk Das ◽  
Nhu Ngo ◽  
Sarah M. Nielsen ◽  
Scott T. Michalski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Diagnostic Yield ◽  
Gene Mutations ◽  
Breast Cancer Diagnosis ◽  
Consecutive Series ◽  
Breast Cancer Patients ◽  
Tumor Sequencing ◽  
Germline Testing

1092 Background: Germline genetic testing is recommended for breast cancer patients with specific presentations or family histories. Separately, tumor DNA sequencing is increasingly used to inform therapy, most often in patients with advanced disease. Recent NCCN and ESMO guidelines recommend germline testing following somatic testing, under specific circumstances and for specific genes. We examined the utility of germline findings in patients referred for both test modalities. Methods: We reviewed somatic and germline mutations in a consecutive series of patients who: (a) had a current or previous breast cancer diagnosis, (b) were referred for germline testing, and (c) previously received tumor sequencing. Diverse reasons for germline testing included: a tumor finding of potential germline origin, treatment or surgical planning, personal or family history, and patient concern. Results: 227 patients met study criteria of whom 88 (39%) harbored a pathogenic germline variant (PGV) in a high or moderate risk cancer predisposition gene. Mutations in certain genes were most likely to be of germline origin, and most PGVs were potentially actionable (Table). 13% of PGVs were not reported by tumor tests as either germline or somatic findings, usually a result of tumor test limitations. Of note, 27 of the patients with PGVs (31%) had these variants uncovered only after presenting with a second, possibly preventable, malignancy. Conclusions: Germline testing following tumor sequencing often yielded findings that may impact care. Indeed, the 39% PGV rate we observed suggests that such testing may be underutilized. We observed actionable PGVs missed by somatic tests, PGVs uncovered in patients’ second malignancies, and PGVs not within germline reflex testing criteria. These results reinforce the utility of germline testing separate from somatic testing in appropriate patients. [Table: see text]

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