Cover Image

Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer

Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer. Design, Setting, and Participants...

Full description

Saved in:
Bibliographic Details
Main Authors: Kemp, Zoe, Turnbull, Alice, Yost, Shawn, Seal, Sheila, Mahamdallie, Shazia, Poyastro-Pearson, Emma, Warren-Perry, Margaret, Eccleston, Anthony, Tan, Min Min, Teo, Soo Hwang, Turner, Nicholas, Strydom, Ann, George, Angela, Rahman, Nazneen
Format: Article
Published: JAMA Network 2019
Subjects:
R Medicine
Online Access:http://eprints.um.edu.my/24217/
https://doi.org/10.1001/jamanetworkopen.2019.4428
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.um.eprints.24217
record_format eprints
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Kemp, Zoe
Turnbull, Alice
Yost, Shawn
Seal, Sheila
Mahamdallie, Shazia
Poyastro-Pearson, Emma
Warren-Perry, Margaret
Eccleston, Anthony
Tan, Min Min
Teo, Soo Hwang
Turner, Nicholas
Strydom, Ann
George, Angela
Rahman, Nazneen
Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
description Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer. Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017. Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes. Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process. Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing.
format Article
author Kemp, Zoe
Turnbull, Alice
Yost, Shawn
Seal, Sheila
Mahamdallie, Shazia
Poyastro-Pearson, Emma
Warren-Perry, Margaret
Eccleston, Anthony
Tan, Min Min
Teo, Soo Hwang
Turner, Nicholas
Strydom, Ann
George, Angela
Rahman, Nazneen
author_facet Kemp, Zoe
Turnbull, Alice
Yost, Shawn
Seal, Sheila
Mahamdallie, Shazia
Poyastro-Pearson, Emma
Warren-Perry, Margaret
Eccleston, Anthony
Tan, Min Min
Teo, Soo Hwang
Turner, Nicholas
Strydom, Ann
George, Angela
Rahman, Nazneen
author_sort Kemp, Zoe
title Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
title_short Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
title_full Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
title_fullStr Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
title_full_unstemmed Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer
title_sort evaluation of cancer-based criteria for use in mainstreambrca1andbrca2genetic testing in patients with breast cancer
publisher JAMA Network
publishDate 2019
url http://eprints.um.edu.my/24217/
https://doi.org/10.1001/jamanetworkopen.2019.4428
_version_ 1665895221113651200
spelling my.um.eprints.242172020-04-23T11:13:46Z http://eprints.um.edu.my/24217/ Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer Kemp, Zoe Turnbull, Alice Yost, Shawn Seal, Sheila Mahamdallie, Shazia Poyastro-Pearson, Emma Warren-Perry, Margaret Eccleston, Anthony Tan, Min Min Teo, Soo Hwang Turner, Nicholas Strydom, Ann George, Angela Rahman, Nazneen R Medicine Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer. Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017. Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes. Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process. Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing. JAMA Network 2019 Article PeerReviewed Kemp, Zoe and Turnbull, Alice and Yost, Shawn and Seal, Sheila and Mahamdallie, Shazia and Poyastro-Pearson, Emma and Warren-Perry, Margaret and Eccleston, Anthony and Tan, Min Min and Teo, Soo Hwang and Turner, Nicholas and Strydom, Ann and George, Angela and Rahman, Nazneen (2019) Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer. JAMA Network Open, 2 (5). e194428. ISSN 2574-3805 https://doi.org/10.1001/jamanetworkopen.2019.4428 doi:10.1001/jamanetworkopen.2019.4428
score 13.211869

Similar Items