Disparities in gynecologic cancer genetics evaluation

Hinchcliff, Emily; Bednar, Erica M.; Lu, Karen H.; Rauh‐Hain, J. Alejandro

doi:10.1016/j.ygyno.2019.01.024

Cited by 65 publications

(44 citation statements)

References 62 publications

(79 reference statements)

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“…Overall, we found that germline and somatic BRCA1/2 mutations had prevalence rates of 20.3 and 4.1%, respectively. Disparities in both germline and somatic testing exist (44,45). Regarding other Chinese studies, our germline mutation prevalence approximated the values reported by Li (35).…”

Section: Discussionsupporting

confidence: 84%

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

You

et al. 2020

Front. Oncol.

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Objective: Despite several nationwide cohort studies of germline BRCA1/2 mutations and several small cohort studies of somatic BRCA1/2 mutations in Chinese epithelial ovarian cancer (EOC) patients, little is known about the impact of these findings on survival outcomes in this population. In this study of 172 retrospectively recruited Chinese EOC patients, germline and somatic BRCA1/2 mutations and their value for predicting survival outcomes were evaluated. Methods: Unselected patients who visited the study center from January 1, 2011, to January 1, 2015, were recruited and asked to provide peripheral blood samples for this study if they were pathologically confirmed to have primary EOC. All patients received staging surgeries or debulking surgeries involving systemic platinum-based chemotherapy, and the patients were then followed up to December 1, 2017. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections and peripheral blood and sequenced for somatic and germline testing, respectively. The demographic and clinicopathological characteristics of the patients were collected to analyze the distribution of BRCA mutations in subgroups. Survival outcomes were compared among various BRCA mutation statuses using univariate and multivariate models. Results: In 58 (33.7%) patients, 63 variants were identified, including variants of unknown significance (VUS) in 18 patients (10.5%) and pathogenic or likely pathogenic variants in a partially overlapping set of 41 patients (23.8%). Germline BRCA mutations, somatic BRCA mutations, BRCA1 mutations in general, and BRCA2 mutations in general were found in 35 (20.3%), 7 (4.1%), 28 (16.3%), and 13 (7.6%) patients, respectively. Five recurrent mutations were identified. Personal and family cancer histories as well as hereditary breast and ovarian cancer (HBOC) criteria were associated with deleterious BRCA mutations both overall and in the germline specifically, whereas only age at diagnosis of EOC was associated with somatic BRCA mutations. In univariate and Cox regression analyses, patients with BRCA1/2 mutations in general had significant improvements in progression-free survival (PFS) and overall survival (OS). You et al. Germline and Somatic BRCA1/2 Mutations in EOC Conclusions: In Chinese EOC patients, the distributions and risk factors associated with germline and somatic BRCA1/2 mutations were similar to those previously reported in international studies. Deleterious BRCA mutations in general were associated with improved survival outcomes in this cohort.

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Section: Discussionsupporting

confidence: 84%

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

You

et al. 2020

Front. Oncol.

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“…Previous studies have identified several barriers to genetic counseling and to obtaining accurate family histories. These include a lack of awareness of the goal of having genetic services, inaccurate cancer risk perception, poor communication, limited knowledge of family histories, and time commitments to both travel to and attend genetics or other medical appointments . There is further controversy regarding the appropriate time for undergoing counseling.…”

Section: Discussionmentioning

confidence: 99%

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

Kahn

Gordhandas

Maddy

et al. 2019

Cancer

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BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling. Cancer 2019;125:3172-3183.

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“…It should be emphasized that since 2015, the D99 exemption code has been introduced, which permits free access to the surveillance program for healthy women at high risk because they are BRCA gene mutation carriers. Therefore all issues related to individuals with genetic variants should be understood and made explicit to all health operators to have the possibility of intervention on the economic resources to target inherited breast cancer, as well as the related human, psychological, genetic, and management issues [123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142].…”

Section: Discussionmentioning

confidence: 99%

The Role of Genetic Counseling in Gynecological Oncology

Comparetto¹,

Dupré²,

Borruto³

2019

obm genet

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Background: Clinical or medical genetics deals with the study and diagnosis of genetic diseases. It is oriented to the formulation of the clinical diagnosis of genetic diseases and genetic counseling to evaluate the possible reproductive risk for the patient and his/her family. The geneticists here play a role in the diagnosis and prevention of some of the diseases occurring most frequently, such as cancer and cardiovascular diseases. Methods: State-of-the-art through literature review. Results: Genetic counseling helps consultants make decisions regarding the possibility of developing and/or transmitting genetic diseases, to evaluate the possible choices that can be made once genetic testing has been carried out and its result is known (possible therapies, voluntary pregnancy interruption, etc.). The decision on what to do is always autonomous to the consultants and the doctor or, a qualified professional figure has no role in it. Genetic

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Disparities in gynecologic cancer genetics evaluation

Cited by 65 publications

References 62 publications

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

The Role of Genetic Counseling in Gynecological Oncology

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