Germline cancer susceptibility mutations in older women with breast cancer (BC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13030-e13030
Author(s):  
Yanin Chavarri Guerra ◽  
Sharon Sand ◽  
Sandra Brown ◽  
Carolyn B. Hendricks ◽  
Mary Hander ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Older Women ◽  
Clinical Characteristics ◽  
Research Network ◽  
Community Research ◽  
Gene Variants ◽  
Risk Gene ◽  
Germline Variant ◽  
History Of

e13030 Background: Older women with BC are less likely to undergo genetic cancer risk assessment since a hallmark of hereditary BC is younger age at onset. Hence there are limited data regarding genetic risk assessment findings in older women with BC. We analyzed the clinical characteristics and germline variant profiles of women with history of BC referred for genetic counseling at age ≥ 65 years, enrolled in the Clinical Cancer Genomics Community Research Network registry. Methods: Women age ≥ 65 with a history of BC (invasive or ductal carcinoma in situ) who underwent genetic testing from 1997 to 2016 were included. The profile of those found to have BC-related pathogenic variants was analyzed. Demographic and clinical characteristics for those with and without germline variants were compared using Fisher’s test and x2statistics. Results: 1372 women age ≥ 65 with BC were identified. Genetic testing was performed in 75% (n = 1035), among whom 10.4% (n = 108) had a germline variant in a BC-associated gene. High risk gene variants accounted for 85.1% (n = 92): BRCA2 (41.6%, n = 45), BRCA1 (37%, n = 40), PALB2 (5.5%, n = 6) and TP53 ( < 1%, n = 1). Moderate risk gene variants were identified in 16.6% (n = 18): CHEK2 (13.8%, n = 15), ATM (1.8%, n = 2) and NF1 ( < 1%, n = 1). Mean age at BC diagnosis was 56.4 (range 29 - 84) for women with variants and 60.9 (range 20 - 90) for those without (p < .001). 25.9% of women with variants (n = 28) had their first BC diagnosed ≥ age 65, of which 60.7% (n = 17) were BRCA2 and 21.4% (n = 6) were BRCA1 mutations ( BRCA2 was significantly higher in women diagnosed with BC age ≥ 65 [p < .001]). There was no difference in the mean number of 1st, 2nd and 3rd degree relatives with BC (2.4 [range 0-10] vs 2.2 [range 0-15]) for women with and without variants, respectively, and no difference in stage at diagnosis (Stage I-II in 95% vs 89.5%, p = .4). Women with variants were less likely to have ER/PR positive tumors than those without (66% vs 81.6%, p = .01). Conclusions: BC related susceptibility variants, particularly in BRCA2, are found in a significant number of older women undergoing genetic testing for a first diagnosis of BC ≥ 65. Older women with a clinical suspicion of hereditary BC should not be excluded from genetic testing and counseling based on chronological age alone.

Prevalence of BRCA2 mutations and other clinical characteristics in women with triple-negative breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 160-160
Author(s):  
Jennifer Chun ◽  
Freya Ruth Schnabel ◽  
Shira Schwartz ◽  
Jessica Billig ◽  
Karen Hiotis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Personal History ◽  
Breast Cancers ◽  
History Of ◽  
Brca2 Mutations

160 Background: Triple-negative breast cancers (TNBC) represent 10%–20% of invasive breast cancers. Current guidelines recommend genetic testing for women who are diagnosed with TNBC. Studies have shown that BRCA1 mutations are associated with TNBC, but there is little information on the relationship of BRCA2 mutations and TNBC. The purpose of this study was to look at the clinical characteristics of TNBC compared to non-TNBC in a cohort of women with newly diagnosed breast cancer. Methods: The Breast Cancer Database at our institution was queried for patients with invasive breast cancer. We included the following variables: age, race, BRCA1,2, tumor characteristics, and personal history of breast cancer (PHBC). Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: Out of a total of 1,332 women, 125 (9%) had TNBC. The median age for both TNBC and non-TNBC was 59 years. Majority of women had early stage breast cancer (92%) with ductal carcinoma (80%). There was a significantly higher proportion of Blacks and Asians with TNBC (p < 0.0001). Women with TNBC had higher Ki-67 (p < 0.0001). Within the TNBC group, there were 12 (29%) patients who tested positive for BRCA1,2 mutation and 23 (8%) who tested positive for BRCA 1,2 mutations in the non-TNBC group. Interestingly, BRCA1 was not associated with TNBC (p = 0.40) and BRCA2 was significantly associated with TNBC (p < 0.0001). We also found a higher proportion of TNBC in women who had a PHBC (p = 0.01). Conclusions: In our study, women with TNBC were similar in age to women who did not have TNBC. We found that the women with TNBC in our cohort had elevated rates of BRCA2 mutations. We also found that women with a personal history of breast cancer were at risk for developing TNBC. This may be related to the use of hormonal therapy that reduces the risk of ER/PR-positive tumors. Women of all ages are at risk for developing TNBC and older age at TNBC should not deter from genetic testing.

Clinical characteristics of men with prostate cancer and evaluation of NCCN prostate cancer guidelines on germline genetic testing outcomes.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 252-252
Author(s):  
Samantha Greenberg ◽  
Brock O'Neil ◽  
Kathleen A. Cooney ◽  
Lisa M. Pappas ◽  
Jonathan David Tward
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Clinical Characteristics ◽  
Genetic Counselor ◽  
Clinical Information ◽  
Risk Groups ◽  
Genetic Test Results ◽  
History Of

252 Background: Growing evidence suggests up to 12% of men with metastatic prostate cancer (PC) harbor a pathogenic variant (PV) in genes associated with hereditary cancer risk. Updated NCCN PC guidelines include consideration for germline testing (GT) in men with high risk, very high risk, regional, or metastatic PC. As a result, we expanded our criteria for GT in men with PC to include these groups and men with a strong family history for PC beginning in January 2018. This study reports the clinical characteristics and germline findings before and after this expansion. Methods: Men with PC underwent multi-gene genetic testing (GT) for PVs from June 2016-June 2018 with genetic counselors. Clinical information and germline GT results were analyzed. Results: Of 285 eligible men who met with a genetic counselor, there were 201 evaluable GT results. One PV was excluded for suspicion of clonal hematopoiesis of indeterminate potential. Twenty-seven PVs were identified in 24 men (12.4%). Three men had two PVs identified (1.5%), at least one PV of which was in ATM or BRCA2. The most common PVs were ATM (n = 6, 3.0%), BRCA2 (n = 7, 3.5%), MYH (n = 4, 2.0%), and HOXB13 (n = 4, 2.0%). Rate of PVs were not statistically different across the two timeframes of GT, (2016-17, 14%; 2018, 11.2%; p = 0.60). PVs were not statistically associated with a higher ISUP group (1-3: 10.1%, 4-5: 13.6%; p = 0.49) and were distributed across multiple NCCN risk groups. Almost all men tested reported a family history of cancer, with the most frequent cancers reported including PC (n = 79, 39.3%), breast (n = 55, 27.4%), and colon cancer (n = 23, 11.4%). Family history of PC was not statistically associated with genetic test results (PV: 54%, no PV: 37%; p = 0.11). Conclusions: Expanding germline GT criteria will substantially increase patient volume without significant changes to the PV rate. Higher PC risk defined by ISUP or NCCN was not associated with the rate of PVs. Given this finding, further broadening the criteria for GT in PC may be warranted.

scholarly journals Characteristics and long-term outcomes of childhood glaucoma: a retrospective-cohort study

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 165
Author(s):  
Supawan Surukrattanaskul ◽  
Pukkapol Suvannachart ◽  
Sunee Chansangpetch ◽  
Anita Manassakorn ◽  
Visanee Tantisevi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Secondary Glaucoma ◽  
Research Network ◽  
Congenital Glaucoma ◽  
Long Term Outcomes ◽  
History Of ◽  
The Mean ◽  
Primary Glaucoma

Purpose: To evaluate the clinical characteristics and treatment outcomes of patients with childhood glaucoma. Methods: We retrospectively reviewed the data of patients with childhood glaucoma who visited the glaucoma clinics at the Queen Sirikit National Institute of Child Health and the King Chulalongkorn Memorial Hospital between January 2008 and January 2018. The diagnosis was based on the Childhood Glaucoma Research Network classification. We recorded their clinical characteristics and requirement of any glaucoma interventions. Results: A total of 691 eyes from 423 patients were included in this study. The patients predominantly comprised boys. The average follow-up duration was 71.3±63.8 months. The mean age at presentation was 3.9±4.4 years. Most patients presented with a high initial intraocular pressure (IOP) of 28.5±11.2 mmHg. Glaucoma associated with non-acquired ocular anomalies (22.9%) was the most common subtype, followed by primary congenital glaucoma (20.8%). We recorded a family history of glaucoma in 6.4% of patients. Most patients had bilateral glaucoma (63.4%) and required at least one intervention (51.5%). The average IOP at the latest follow-up visit was 19.1±10.8 mmHg. All glaucoma types had significantly lower IOP, compared to that at their baselines (all p<0.001). Moreover, most patients had an unfavourable visual acuity (49.5%) at their latest visit. Conclusions: Secondary glaucoma associated with non-acquired ocular anomalies is the most common subtype of glaucoma. All subtypes, including primary glaucoma, were sporadic. The majority of patients had unfavourable visual outcomes. These real-world findings are fundamental to acquire a better understanding of childhood glaucoma.

Maintaining access to genomic cancer risk assessment (GCRA) during the COVID-19 pandemic using telemedicine in a resource-limited setting.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 286-286
Author(s):  
Yanin Chavarri Guerra ◽  
Maria Fernanda Ochoa Chavez ◽  
Andrés Rodríguez-Faure ◽  
Alfredo Pherez Farah ◽  
Enrique Soto Perez De Celis ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Risk Reduction ◽  
Cancer Genetics ◽  
Resource Limited Setting ◽  
Research Network ◽  
Phone Call ◽  
Community Research ◽  
Resource Limited ◽  
Family Medical History ◽  
Limited Setting

286 Background: COVID-19 has disrupted cancer care services globally, and particularly in low- and middle-income countries. The cancer genetics clinic at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán has provided GCRA for over 1000 underserved Mexican patients with cancer since 2017 through a collaboration with the Clinical Cancer Genomics Community Research Network (CCGCRN). During the COVID-19 pandemic, in-person clinic visits were suspended, and telemedicine emerged as a potential way to provide GCRA while reducing the risk of COVID-19. Here, we report our experience using telemedicine to provide GCRA in a resource-limited setting. Methods: During the COVID-19 pandemic, new patients meeting criteria for GCRA were invited to join the CCGCRN via phone call. Candidates received detailed information regarding the protocol procedures and multigene genetic testing. Those who accepted were sent an electronic consent form, family medical history forms, and risk reduction questionnaires to be completed before their appointment. Blood testing was performed during a short visit to the hospital, or mailed by the patient. Patients who had already received GCRA and genetic testing prior to the start of the pandemic were contacted to cancel their in-person appointment and to schedule a telemedicine visit. According to patient preferences and availability, results were disclosed via phone call, video call, or teleconferencing software employing end-to-end encryption communication apps. Results: Between July 2020 and May 2021, 273 new patients fulfilling GCRA criteria were invited to the CCGCRN protocol. Median age at the time of enrollment was 44 years (range 27-66), 87% (n = 237) were women, and 68% (n = 187) had a personal history of cancer (90% breast). Eighty-three percent of new patients (n = 227) completed all the protocol procedures. Median length of the enrollment phone call was 10 minutes (range 4-71 min). During the same period, 439 genetic testing results (including those of patients who received GCRA before the pandemic and of new patients) were disclosed: 356 were negative and 83 had a pathogenic variant (PV). Ninety-nine percent of patients with negative testing received their results via phone call, and 96% were sent a digital written report. For patients with a PV, 80% of results were disclosed via videoconferencing platforms (WhatsApp or Zoom). All patients with PV were sent a digital written report, risk reduction and early detection recommendations, a family letter, and specific PV information. Conclusions: Providing access to GCRA and testing using readily-available telemedicine platforms proved feasible in a resource-limited setting during the COVID-19 pandemic. Our results show that telemedicine represents an excellent method to identify, recruit, and test patients meeting criteria for GCRA, and to provide genetic testing results.

scholarly journals Prevalence of pathogenic variants in DNA damage response genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer

2020 ◽  
Author(s):  
Tiffiney R. Hartman ◽  
Elena V. Demidova ◽  
Randy W. Lesh ◽  
Lily Hoang ◽  
Marcy Richardson ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Dna Damage ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Dna Damage Response ◽  
Early Onset ◽  
Personal History ◽  
Pathogenic Variants ◽  
Damage Response ◽  
History Of

ABSTRACTPurposePathogenic variants (PVs) in a number of genes are known to increase the risk of hereditary renal cancer (hRC). However, many early-onset RC (eoRC) patients undergoing genetic testing lack PVs in hRC genes; thus, their genetic risk remains undefined. To determine if PVs in DNA damage response (DDR) genes are enriched in a convenience sample of eoRC patients undergoing genetic testing.Materials and MethodsRetrospective review of results for 844 unselected eoRC patients, undergoing genetic testing with a multi-gene cancer panel by Ambry Genetics [between July 2012 and December 2016]. The patients were tested with CancerNext and/or CancerNext Expanded panels for a variety of indications. Identified PVs were compared with patient characteristics.ResultsMean age of RC diagnosis was 48 years [range 24-60]. In addition to eoRC, 57.9% patients tested reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). PVs in cancer risk genes were identified in 12.8% of patients—3.7% in RC-specific genes, and 8.55% in DDR genes. DDR gene PVs were most commonly identified in CHEK2, BRCA1/2, and ATM. Among the 2.1% of patients with a BRCA1/2 PV, <50% reported a personal history of hereditary breast/ovarian-associated cancer. No association between age of RC diagnosis, and prevalence of PVs in RC-specific or DDR genes was observed.ConclusionsMulti-gene panel testing including DDR genes may provide a more comprehensive risk assessment in unselected eoRC patients, and their families. Validation in larger datasets is needed to characterize the association with eoRC.

Genetic, clinical and pathological characteristics of BRCA-associated breast cancer (BC) in Hispanic patients in the United States (US) and Latin America (LatAm).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1539-1539
Author(s):  
Yanin Chavarri Guerra ◽  
Sharon Sand ◽  
Marcia Cruz Correa ◽  
Pamela Ganschow ◽  
Nancy Cohen ◽  
...  
Keyword(s):  
Cancer Genomics ◽  
Hispanic Women ◽  
The United States ◽  
Research Network ◽  
Community Research ◽  
Brca Mutations ◽  
Younger Age ◽  
The Us ◽  
Hispanic Patients ◽  
History Of

1539 Background: Hispanic women with BC present at a younger age, have a higher frequency of BRCA mutations and show a worse incidence-to-mortality ratio than non-Hispanic women. Information regarding the characteristics of BRCA-associated BC in Hispanics is limited. Here, we assess differences in BRCA-associated BC between Hispanic patients in the US and in LatAm. Methods: Hispanic patients from the US and LatAm (Mexico, Colombia, Peru, and Puerto Rico) with a history of BRCA-associated BC enrolled in the Clinical Cancer Genomics Community Research Network registry were included. We compared the genetic, demographic, clinical and pathologic characteristics between Hispanics from the US and LatAm using Fisher’s exact test and x2statistics. Results: Between 1997 and 2016, 3670 Hispanic patients with a history of BC from LatAm (n = 1341) and the US (n = 2329) were identified, of which 490 (13.3%) had a deleterious BRCA mutation. The frequency of BRCA mutations was similar in Hispanics from LatAm (13.8%, n = 185) and the US (13.1%, n = 305). No significant differences were found in the frequency of BRCA1 vs BRCA2 mutations between patients from LatAm (BRCA1 68%, BRCA2 31.8%) and the US (BRCA1 61.3%, BRCA2 39%) (p = .12). The most frequent mutations found in BRCA1 were: ex 9-12del (LatAm n = 24, US n = 15), 185delAG (LatAm n = 13, US n = 18) and 943ins10 (LatAm n = 3, US n = 8), and in BRCA2 3492insT (LatAm n = 3, US n = 28). Mean age at BC diagnosis was 39.1 (SD 9.5) in LatAm and 41.7 (SD 10.6) in the US (p = 0.01). US patients were significantly more likely to present with Stage 0-II BC than those from LatAm (77.1% vs. 47.6%, p < .001). We found no differences in the proportion of hormone receptor positive tumors between patients from LatAm (45%) and the US (47%) (p = .78). Conclusions: The frequency of BRCA-associated BC was similar between Hispanics in LatAm and the US. Women from LatAm with BRCA mutations present at a younger age, as seen for sporadic BC; the causes for this finding warrant further research. Women with BRCA-associated BC in LatAm are more likely to have advanced BC at presentation, which may be a reflection of disparities and barriers in access to care.

scholarly journals Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey

2021 ◽  
pp. 1-11
Author(s):  
Sukh Makhnoon ◽  
Robert Yu ◽  
Sonia A. Cunningham ◽  
Susan K. Peterson ◽  
Sanjay Shete
Keyword(s):  
Risk Assessment ◽  
Health Care ◽  
Genetic Testing ◽  
Health Care Providers ◽  
Public Awareness ◽  
Personal History ◽  
Cancer Risk Assessment ◽  
Care Providers ◽  
Cancer Genetic ◽  
History Of

<b><i>Introduction:</i></b> Discussion of cancer genetic testing with health-care providers (HCPs) is necessary to undergo testing to inform cancer risk assessment and prevention. Given the rapid evolution in genetic testing practice in oncology, we describe the current landscape of population-level cancer genetic testing behaviors. <b><i>Methods:</i></b> A questionnaire including items regarding discussion of cancer genetic testing with HCPs was administered to a nonprobability sample (<i>N</i> = 2,029) of the Texas population. <b><i>Results:</i></b> Overall, 11% of respondents discussed cancer genetic testing with HCPs. In multivariable analysis, discussion was significantly related to having a personal history of breast/ovarian/colon cancer (OR = 11.57, 95% CI = 5.34–25.03), personal history of other cancer (OR = 3.18, 95% CI = 1.69–5.97), and health information-seeking behaviors (OR = 1.73, 95% CI = 1.12–2.66). Surprisingly, respondents who believed that inherited predispositions in addition to other modifiable risk factors cause cancer were less likely to discuss genetic testing compared to those who did not believe that inherited cancer predispositions cause cancer (OR = 0.54, 95% CI = 0.36–0.79). <b><i>Discussion:</i></b> The high discussion rate may be attributed to increased public awareness of genetic testing and adoption of more inclusive clinical genetic testing guidelines. The findings suggest that efforts to increase public awareness of the utility of genetic testing on personalized cancer risk assessment and cancer prevention are needed.

scholarly journals Characteristics and long-term outcomes of childhood glaucoma: a retrospective-cohort study

F1000Research ◽  
2022 ◽  
Vol 10 ◽  
pp. 165
Author(s):  
Supawan Surukrattanaskul ◽  
Pukkapol Suvannachart ◽  
Sunee Chansangpetch ◽  
Anita Manassakorn ◽  
Visanee Tantisevi ◽  
...  
Keyword(s):  
Family History ◽  
Clinical Characteristics ◽  
Secondary Glaucoma ◽  
Research Network ◽  
Congenital Glaucoma ◽  
Long Term Outcomes ◽  
History Of ◽  
The Mean

Purpose: To evaluate the clinical characteristics and treatment outcomes of patients with childhood glaucoma. Methods: We retrospectively reviewed the data of patients with childhood glaucoma who visited the glaucoma clinics at the Queen Sirikit National Institute of Child Health and the King Chulalongkorn Memorial Hospital between January 2008 and January 2018. The diagnosis was based on the Childhood Glaucoma Research Network classification. We recorded their clinical characteristics and requirement of any glaucoma interventions. Results: A total of 691 eyes from 423 patients were included in this study. The patients predominantly comprised boys. The average follow-up duration was 71.3±63.8 months. The mean age at presentation was 3.9±4.4 years. Most patients presented with a high initial intraocular pressure (IOP). The average intial IOP of all patients was 28.5±11.2 mmHg. Glaucoma associated with non-acquired ocular anomalies (22.9%) was the most common subtype, followed by primary congenital glaucoma (20.8%). We recorded a family history of glaucoma in 6.4% of patients of the 234 patients with an available family history. Most patients had bilateral glaucoma (63.4%) and required at least one intervention (51.5%). The average IOP at the latest follow-up visit was 19.1±10.8 mmHg. All glaucoma types had significantly lower IOP, compared to that at their baselines (all p<0.001). Moreover, most patients had an unfavourable visual acuity (49.5%) at their latest visit. Conclusions: Secondary glaucoma associated with non-acquired ocular anomalies is the most common subtype of glaucoma. The majority of patients had unfavourable visual outcomes. These real-world findings are fundamental to acquire a better understanding of childhood glaucoma.

scholarly journals Determination of Relapse Risk By Complement Gene Variants after Eculizumab Discontinuation in Complement-Mediated Thrombotic Microangiopathy: A Retrospective Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Aldo A. Acosta-Medina ◽  
Ann M. Moyer ◽  
Ronald S. Go ◽  
Maria Alice V. Willrich ◽  
Hassan B. Alkhateeb ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Thrombotic Microangiopathy ◽  
Univariate Analysis ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Treatment Schedule ◽  
Gene Variants ◽  
Increased Risk ◽  
History Of ◽  
Complement Gene ◽  
The Impact

Background Eculizumab, a monoclonal antibody targeting C5, is an effective treatment for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy has been suggested, the optimal treatment schedule is unknown, while eculizumab discontinuation does not universally lead to relapse. Data evaluating risk factors associated with an increased risk of CM-TMA recurrence following eculizumab withdrawal are scarce. Prior to the eculizumab era, complement genetic studies have been used to assess morbidity and mortality in patients with CM-TMA. Our aim was to assess the impact of complement gene variants on CM-TMA relapse rate (RR) after eculizumab discontinuation. Methods Search protocols were developed for the Ovid and PubMed databases to identify existing reports on CM-TMA and eculizumab withdrawal published before February 1st 2020. Cases were cross-referenced to eliminate duplicates. Inclusion criteria included patients diagnosed with CM-TMA who had undergone eculizumab discontinuation. Reasons for exclusion were patients with no follow-up after eculizumab withdrawal and patients lacking complement gene testing. Patients undergoing eculizumab dose extension, but not discontinuation, were not included. Results Fifteen studies including 557 individuals were retrieved. Of these, 363 (65.2%) were excluded as outlined in Figure 1 and 194 cases were included in the final analysis with a global RR of 28.9% (n=56). Distribution based on gene impacted and variant type are presented in Table 1. RR was highest among patients with CFH variants (52.5% to 60%) -particularly if involving exon 22 or nonsense mutations-, MCP/CD46 variants (38.9% to 45%) -particularly if affecting splice regions-, and cases with multiple concomitant variants (57.1%) -particularly those including CFH or a CFH-CFHR1 Hybrid (Table 2). Patients with relapse were more likely to have the presence of a complement variant (p&lt;0.001), history of previously resolved CM-TMA events (p=0.022), younger age (mean age 22.4 years for patients with relapse vs. 32.33 years for patients without relapse; p=0.002) and, within those with detected variants, multiple vs. single variants (p=0.002) and CFH-inclusive variants (p=0.003). On univariate analysis, complement gene variants (OR 4.217 95%CI 1.97-9.026; p&lt;0.001), age &lt;30 years (OR 2.346 95%CI 1.159-4.749; p=0.018), and presence of multiple variants (OR 2.06 95%CI 1.172-3.621; p=0.012) or CFH-inclusive variants (OR 3.111 95%CI 1.443-6.71; p=0.004) were associated with increased odds of CM-TMA relapse, while no prior history of additional CM-TMA events was the only factor associated with lower RR (OR 0.327 95%CI 0.123-0.87; p=0.025). Presence of complement variants (OR 4.48 95%CI 1.132-17.724; p=0.033) and CFH-inclusive variants (OR 3.045 95%CI 1.136-8.159; p=0.027) were independently associated with increased RR on multivariate analysis (Table 3). Conclusion Relapse after eculizumab discontinuation is rare in cases with no genetic variants identified but can increase to more than 80% in high-risk subgroups. Complement genetic testing is not required for CM-TMA diagnosis or for initiation of complement inhibiting therapy; however, our results demonstrate the value of complement genetic testing when stratifying risk of patients for consideration of eculizumab discontinuation. Disclosures Sridharan: Alexion: Honoraria.

Communication of genetic testing results and cascade testing among Mexican carriers of cancer-associated variants and their families.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13541-e13541
Author(s):  
Yanin Chavarri Guerra ◽  
Andrés Rodríguez-Faure ◽  
Laura Margarita Bolano Guerra ◽  
Jose Luis Rodriguez Olivares ◽  
Jazmin Arteaga ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Latin American ◽  
Family Involvement ◽  
Medical Information ◽  
Cancer Genomics ◽  
Family Members ◽  
Research Network ◽  
Community Research ◽  
Cascade Testing ◽  
Results Disclosure

e13541 Background: Most hereditary cancer syndromes exhibit autosomal dominant inheritance. Therefore, communicating results to family members and performing cascade testing is crucial in order to identify individuals at risk and offer them appropriate risk-reducing strategies. The process of communicating medical information within families is highly variable and might be affected by several factors (including culture, education, understanding of results, and family conflicts) which remain understudied among individuals living in developing countries. We sought to investigate communication of results and cascade testing reach within the families of Mexican individuals carrying cancer-associated pathogenic variants (PVs). Methods: Individuals seen at a single center in Mexico City carrying a cancer-associated PV and enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) were included. Carriers received genetic counseling at the time of results disclosure, a family letter was provided to facilitate the communication of results, and cascade testing was offered. After >3 months from results disclosure, participants were surveyed regarding genetic testing results communication patterns, performance of cascade testing, and surveillance behaviors. Data was analyzed using descriptive statistics. Results: Among 354 probands, 53 (15%) were identified as carriers of a cancer-associated PV. Mean age was 48.3 (range 21-82) years. Cascade testing (≥1 family member) was initiated in 74% of families (n = 39), with a median of 3 (range 0-16) family members tested per proband. 53 carriers responded the survey (29 probands and 24 relatives). 98% (n = 43) had shared results with their family, and 53% (24/45) had shared them with their treating physicians. Most respondents were receiving active surveillance (n = 36, 80%); with 43% (n = 15) reporting having at least one barrier for complying with surveillance (financial: n = 8; distance to the hospital: n = 3). Around half of the carriers perceived their cancer risk to be of ≥50%. Conclusions: Our results show that both the communication of genetic testing results and the proportion of cascade testing within Mexican families are high. Family involvement in health care decision-making is common in Mexico, as in other Latin American countries, which might lead to improved family communication. However, strategies to improve communication with providers are needed in order to tackle barriers and improve surveillance of individuals carrying cancer associated PVs.

Sign in / Sign up

Export Citation Format

Share Document