scholarly journals Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 370
Author(s):  
Joohyun Hong ◽  
Jiyun Lee ◽  
Minsuk Kwon ◽  
Ji-Yeon Kim ◽  
Jong-Won Kim ◽  
...  
Keyword(s):  
Genetic Testing ◽  
High Risk ◽  
Salt Lake ◽  
Medical Center ◽  
Brca Mutation ◽  
Genetic Diagnosis ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Brca 1 ◽  
Local Laboratory

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline BRCA (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.’s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline BRCA mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. “Discordant: Opposite classification” was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of BRCA 1 by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. “Discordant: Laboratory’s uncertain classification” was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required.

The follow-up sought after diagnosis of a BRCA-1 or BRCA-2 mutation.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 57-57
Author(s):  
Karinn Marie Chambers ◽  
Edward Joey Armstrong ◽  
Teresa Flippo ◽  
Terry Sarantou ◽  
Frederick L. Greene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Medical Center ◽  
Brca Mutation ◽  
Increased Risk ◽  
Brca 1 ◽  
Long Term Follow Up ◽  
High Risk Breast

57 Background: A woman with a known BRCA mutation has a lifetime risk for the development of breast cancer of up to 80%. Carolinas Medical Center cares for approximately 600 breast cancer patients annually with genetic testing offered to those patients whose history meets commonly established criteria. This study seeks to document the follow-up patients with BRCA mutations most commonly undertake at our facility. Methods: This study is a retrospective review of all patients who underwent genetic testing at Carolinas Medical Center and who were found to be positive for a mutation in the BRCA gene. Since 1996 our genetics group has tested 2056 individuals, of these 246 (12%) carry a mutation of the BRCA-1 and/or BRCA-2 gene. 102 of these 246 patients (41%) had no evidence of cancer at the time of genetic testing. 144 of these 246 patients (59%) did carry a diagnosis of cancer at the time of genetic testing. Results: Of the 246 patients who tested positive for a deleterious mutation in the BRCA gene 204 (83%) had documented follow-up after their diagnosis. 140 of those 204 patients (69%) had documented initial follow-up appointments to discuss their diagnosis. 63 patients of the 140 (45%) who sought initial consultation met with a surgeon. 73 of these 140 patients (52%) had their initial consultation with a Gyn/Oncologist. 3 patients had their initial consultation with a medical oncologist and the remaining patient with their primary care physician. Documentation was available for 131 of the 204 patients (64%) in regards to follow up related to their risk of breast cancer development, 129 of those patients were being followed by a high risk breast provider. 126 of the 204 patients (62%) with long term follow-up were being followed by a Gyn/Oncologist secondary to their increased risk for ovarian cancer. This data includes all patients regardless of the decisions they made concerning surveillance or prophylactic surgery. Conclusions: The majority of the patients at Carolinas Medical Center who have tested positive for a BRCA mutation have sought long term follow-up with both a high risk breast provider and a Gyn/Oncologist in regards to their increased risk for the development of both breast and ovarian cancer.

Racial disparities in genetic testing of breast cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10591-10591
Author(s):  
Solange Bayard ◽  
Yalei Chen ◽  
Genevieve A. Fasano ◽  
Melissa Davis ◽  
Eleanor M. Walker ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Supreme Court ◽  
Brca Mutation ◽  
Distant Recurrence ◽  
Breast Cancer Patients ◽  
Supreme Court Ruling ◽  
Brca Mutations ◽  
Gene Patenting ◽  
Testing Patterns ◽  
Risk Reducing

10591 Background: TNBC is disproportionately prevalent in African American (AA) populations and in women with BRCA-1 germline mutations. BRCA mutation carriers are candidates for targeted therapy with PARP-inhibitors, and testing results may influence risk-reducing surgery choice. Methods: We evaluated genetic testing patterns and outcomes for TNBC patients treated in the prospectively maintained databases of academic cancer programs in two metropolitan cities in the Northeast (New York City, NYC) and Midwest (Detroit, Det), 1998-2018. Median follow up was 3.73 years. Testing patterns were also analyzed by time, comparing pts diagnosed before versus after the mid-2013 Supreme Court ruling that expanded testing availability by banning gene patenting. Results: Of 810 pts, 600 were from NYC and 200 from Det; 202 were AA and 488 WA. Pts undergoing genetic testing were younger (median age 50 vs 62; p < 0.0001). Compared to WA, AA pts were less likely to undergo genetic testing overall (23.8% vs 42.0%; p < 0.0001) and within site (NYC: 25.6% vs 42.8%, p = 0.008; Det: 22.3% vs 38.6%, p = 0.025). No significant differences were seen in frequency of pathogenic BRCA mutations (AA-14.6%; WA-29.3%) or VUSs (AA-6.3%; WA- 4.9%); p = 0.20. Genetic testing disparities were reduced among pts diagnosed after mid-2013 (AA-31.4% vs WA-44.0%; p = 0.01) compared to pre-mid-2013 (AA-18.3% vs WA-40.7%; p < 0.0001). No differences were seen in local or distant recurrence free survival between patients with BRCA, BRCA variants of uncertain significance, non-BRCA mutations, and patients without genetic mutations (local recurrence p = 0.827; distant recurrence p = 0.574). This outcome equivalence was consistent when stratified by WA vs AA identity. Conclusions: Genetic testing has increased for TNBC pts following the mid-2013 Supreme Court ban on gene patenting, but race-associated disparities persist. Pts undergoing genetic testing are more likely to undergo risk-reducing mastectomy, but testing results do not affect survival outcomes, regardless of race. Addressing genetic testing disparities will become increasingly important as mutation-associated targeted therapies are identified through advances in precision medicine.

The combination of capecitabine and cyclophosphamide for metastatic breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12025-e12025
Author(s):  
M. Suzuki ◽  
I. Kimijima ◽  
M. Ishii
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Preclinical Study ◽  
Synergistic Activity ◽  
Breast Cancer Patients

e12025 Background: Capecitabine (X) is converted into 5-FU by thymidine phospholylase (TP). Cyclophosphamide (C) has been shown to make TP higher in the preclinical study. Therefore, the combination of capecitabine and cyclophosphamide (XC) is thought to have a synergistic activity. We explored the efficacy of XC for metastatic breast cancer patients. Methods: 50 metastatic breast cancer patients were treated with XC in our medical center between April 2004 and December 2008. Median patient age was 58 years old (range: 34–79 years old). 36 patients were postmenopausal. X was 1675mg/m2 days 1–21 and C was 67mg/m2 days 1–14 on a 28-day cycle in all-oral combination. This therapy was continued until progression of disease or unacceptable toxicities occurring. Results: Median time to treatment failure was 28 weeks (range: 2–158 weeks). 9 patients were not evaluable for tumor response. Among 41 evaluable patients, complete response (CR) was observed in 2.4% (1 patient) and partial response (PR) was 29.2% (12 patients). Stable disease (SD) was 41.4% (17 patients) and progression of the disease (PD) was 26.8% (11 patients). The objective response rate (CR+PR) was 31.7% and the overall clinical benefit (CR+PR+SDÅÜ24 weeks) was 53.6%. Significant toxicities were uncommon: grade 3 toxicities were encountered for neutropenia in 1 patient, anorexia in 1 patient and hand-foot syndrome in 2 patients. Conclusions: XC is an effective regimen in metastatic breast cancer, and this therapy is of an easy administration and very well tolerated. No significant financial relationships to disclose.

BRCA 1/2 mutations by next-generation sequencing testing in 200 Romanian high-risk patients with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13116-e13116
Author(s):  
Alexandru E. Eniu ◽  
Nicoleta Zenovia Antone ◽  
Andrei Stoian ◽  
Eleonora Dronca ◽  
Ramona DOINA Matei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Prospective Study ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Brca 1 ◽  
Brca1 Brca2 ◽  
High Risk Breast Cancer ◽  
High Risk Breast ◽  
Risk Breast Cancer

e13116 Background: To determine types and frequencies of BRCA 1 (B1) or BRCA2 (B2) mutations in high-risk Romanian breast cancer patients, as there is no data published in this population. Methods: This prospective study evaluates the germline BRCA1/BRCA2 mutations in 200 Romanian high-risk breast cancer patients tested between February 2015-January 2017 at IOCN. Inclusion criteria selected patients diagnosed with breast cancer before 40 years, triple negative breast cancer under the age of 50, or having conventional family history criteria. All patients signed an informed consent. BRCA1/BRCA2 testing was performed using an AmpliSeq-based sequencing analysis, on the Ion Torrent Personal Genome Machine (Life Technologies) at RCFG. The pathogenic mutations were validated using Sanger technology. MLPA was performed for all 200 patients. Results: We analyzed 200 high-risk breast cancer patients and found 32 (16%) patients with pathogenic mutations, 23 (11.5%) patients with B1 and 9 (4.5%) patients with B2 mutations. The majority of patients (99.5%) presented normal MLPA results; only one sample (0.5%) presented a deletion at CHEK2-9(10). The frequency of class 5 mutations identified in B1 gene were c.1687C > T (1%), c.181T > G (2%), c.3607C > T (3.5%), c.4218delG (0.5%), c.5329_5330insC (c.5266dupC) (4.5%) and for the B2 gene c.1528G > T (0.5%), c.4022C > G (0.5%), c.7007G > A (0.5%), c.8695C > T (0.5%), c.9253 delA (0.5%), c.9371A > T (2%). Conclusions: Frequency of deleterious BRCA mutations in our cohort was 11.5% for BRCA1 and 4.5% for BRCA2. This prospective study presents the first extensive results on frequency and types of germline BRCA1/2 mutations in Romanian high-risk breast cancer patients. Clinical trial information: NCT02317120. [Table: see text]

Pathologic findings at risk-reducing salpingo-oophorectomy in germline BRCA mutation carriers: Optimal age of bilateral RRSO.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13046-e13046
Author(s):  
Yong-Man Kim ◽  
Shin-Wha Lee ◽  
Young-jae Lee
Keyword(s):  
Medical Center ◽  
Metastatic Cancer ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Premalignant Lesions ◽  
Mutation Carriers ◽  
Brca 1 ◽  
Brca Mutation Carriers ◽  
Germline Brca Mutation ◽  
Risk Reducing

e13046 Background: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age of 40. Methods: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2013 to 2015. Both fallopian tubes of all cases were examined according to the SEE/FIM protocol and immunohistochemically (IHC) staining was performed when a precursor lesion was suspected. Results: RRSO was performed in 55 patients. The median age at RRSO was 44 years (32–73 years). Of the 36 patients with IHC staining, 7 showed p53 overexpression, 1 showed Ki-67 overexpression, 2 showed serous tubal intraepithelial carcinoma, 2 showed occult cancer, and 1 showed metastatic cancer of breast origin. All occult invasive cancer cases were tubal origin and detected in patients older than 40 years. The detection rate of premalignant lesions or cancer was 21.8% (12/55). Among patients who underwent RRSO under the age of 40, premalignant lesions were found only in BRCA 1 mutation carriers (40.0% vs 0%). In BRCA 2 mutation carriers, premalignant lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of premalignant lesions in BRCA1 mutation carriers. Conclusions: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers, especially in BRCA 1 mutation carriers.

scholarly journals Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer—results from the randomized phase III SUCCESS-A trial

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Amelie de Gregorio ◽  
Lothar Häberle ◽  
Peter A. Fasching ◽  
Volkmar Müller ◽  
Iris Schrader ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Tumor Grade ◽  
Phase Iii ◽  
Primary Study ◽  
Breast Cancer Patients ◽  
Standard Chemotherapy

Abstract Background When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients. Methods A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety. Results No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively. Conclusion Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting. Trial registration Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.

Mutation analysis of PALB2 in high-risk and lower-risk patients negative for BRCA1 and BRCA2 mutations.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 30-30
Author(s):  
Shelly Cummings ◽  
Jenny Peterson ◽  
Elisha Hughes ◽  
Rajesh R. Kaldate ◽  
Sonia Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Patients ◽  
Lower Risk ◽  
Risk Group ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Palb2 Mutation

30 Background: PALB2 has been identified as a breast cancer susceptibility gene conferring ~ 2-4 fold increased risk of breast cancer. A number of studies have estimated the PALB2 mutation prevalence to range from 0.5% - 2.9% in populations of breast cancer patients. We performed an analysis to determine the PALB2 mutation prevalence in a large U.S. referral testing population. Methods: DNA samples were anonymized from two subsets of patients: 955 early onset breast cancer patients with severe family history, and 524 patients with later onset of breast cancer and/or less severe family history. All patients were negative for deleterious sequence mutations or large rearrangements in BRCA1 and BRCA2. Results: We identified 10 disease associated PALB2 mutations in the high risk group of 955 patients and 2 deleterious PALB2 mutations in the lower risk group of 524 patients. Identified PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice site mutation. The mutation prevalence for the high risk population was 1.05% (95% C.I., 0.5 -1.92) whereas that for the lower risk population was 0.38% (95% C.I., 0.05-1.37). The observed rate of PALB2 variants of unknown significance (VUS) identified in this study was ~5% (78 VUS were in 75 of the 1479 patients that were tested). Our variant classification program which successfully decreased the VUS rate in BRCA1 and BRCA2 is similarly expected to enhance mutation classification on an on-going basis for PALB2 genetic testing. Conclusions: Genetic testing for PALB2 may be indicated as a reflex test for breast cancer patients who test negative for BRCA1 and BRCA2.

Strategic integration of genetic testing and counseling in patients with breast cancer in an oncology care model (OCM) multisite community-based practice.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 231-231
Author(s):  
Molly Mendenhall ◽  
Andrew Guinigundo ◽  
Elizabeth Burneka ◽  
Hannah Kolish ◽  
Sarah Mancini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Brca Testing ◽  
Provider Education ◽  
Cancer Genetic ◽  
Nccn Guidelines

231 Background: Despite consensus driven recommendations, data suggests significant non-compliance in breast cancer genetic screening and testing. In the US nearly 300,000 patients are diagnosed with breast cancer annually, of whom approximately one-third are estimated to be BRCA-testing eligible by NCCN guidelines. Of this cohort of patients eligible for testing, it is estimated that again only one-third are ultimately being referred for genetic counseling and testing. Ideally, every patient who is guideline-eligible for testing should be tested, if they consent. The purpose of this project was to integrate and universally apply NCCN genetic breast cancer testing guidelines, building off current OCM processes, to all new breast and/or metastatic breast cancer patients within a large multi-site community oncology practice setting. Methods: Providers utilized directed EHR templates in the setting of an initial diagnosis visit or a treatment planning “OCM visit”. Discreet data fields were created in the EHR to streamline, prompt, and automate this process. Following provider education and uniform physician pre-approval, appropriate patients were reflexively referred to the genetics team for further evaluation and BRCA testing. Adherence to the plan was maintained and measured using data analytic reports and chart audits. Results: OHC’s pre-project eligible patient testing rate (2018) was found to be 20%. Between 1/2019 to 1/2021 1,203 new breast and/or metastatic breast cancer patients were seen and deemed eligible for inclusion, fully 1,200 were screened using NCCN guidelines (99%). Of those screened, 631 patients met the NCCN testing criteria (52.5%). 585 of the 631 were referred to a genetic specialist (92.7%), of those 449 patients were tested (76.7%), 136 patients refused (30%). 22 patients were found to have a BRCA 1 or 2 mutation (5.3%). An additional “halo” effect on other cancer diagnoses was also observed. Screening newly diagnosed breast cancer and metastatic breast cancer patients resulted in a 163% increase in genetic referrals aside from those with breast cancer. Conclusions: Our results suggest a significant overall improvement in breast cancer genetic testing rates. Implemented methods of provider education and awareness of NCCN guidelines imbedded within provider notes, together with discreet data fields in the EHR, proved to be highly effective at screening appropriate patients and ordering subsequent genetic testing; ensuring nearly 100% compliance with current NCCN guidelines for genetic testing. The workflow also resulted in a favorable increase in genetic referrals and testing across other cancers. The patient refusal rate for testing merits further investigation. This structured workflow with reflex genetics referral was effective, scalable, and financially viable to overall genetic and practice growth.

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