Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients

Whitney Espinel; Marjan Champine; Heather Hampel; Joanne Jeter; Kevin Sweet; Robert Pilarski; Rachel Pearlman; Kate Shane; Pamela Brock; Judith A. Westman; Lindsay Kipnis; Jilliane Sotelo; Anu Chittenden; Samantha Culver; Jill E. Stopfer; Katherine A. Schneider; Rosalba Sacca; Diane R. Koeller; Shraddha Gaonkar; Erica Vaccari; Sarah Kane; Scott T. Michalski; Shan Yang; Sarah M. Nielsen; Sara L. Bristow; Stephen E. Lincoln; Robert L. Nussbaum; Edward D. Esplin

doi:10.3390/cancers14102426

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients

Whitney Espinel, Marjan Champine, Heather Hampel, Joanne Jeter, Kevin Sweet, Robert Pilarski, Rachel Pearlman, Kate Shane, Pamela Brock, Judith A. Westman, Lindsay Kipnis, Jilliane Sotelo, Anu Chittenden, Samantha Culver, Jill E. Stopfer, Katherine A. Schneider, Rosalba Sacca, Diane R. Koeller, Shraddha Gaonkar, Erica VaccariSarah Kane, Scott T. Michalski, Shan Yang, Sarah M. Nielsen, Sara L. Bristow, Stephen E. Lincoln, Robert L. Nussbaum, Edward D. Esplin

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

Original language	English
Article number	2426
Journal	Cancers
Volume	14
Issue number	10
DOIs	https://doi.org/10.3390/cancers14102426
State	Published - May 1 2022

Keywords

DNA damage repair
breast cancer
clinical management
clinical utility
genetic testing
moderate-risk genes
ovarian cancer

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10.3390/cancers14102426

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Espinel, W., Champine, M., Hampel, H., Jeter, J., Sweet, K., Pilarski, R., Pearlman, R., Shane, K., Brock, P., Westman, J. A., Kipnis, L., Sotelo, J., Chittenden, A., Culver, S., Stopfer, J. E., Schneider, K. A., Sacca, R., Koeller, D. R., Gaonkar, S., ... Esplin, E. D. (2022). Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients. Cancers, 14(10), Article 2426. https://doi.org/10.3390/cancers14102426

@article{e365762037f0481aacde97bc73fa0984,

title = "Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients",

abstract = "Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients{\textquoteright} family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.",

keywords = "DNA damage repair, breast cancer, clinical management, clinical utility, genetic testing, moderate-risk genes, ovarian cancer",

author = "Whitney Espinel and Marjan Champine and Heather Hampel and Joanne Jeter and Kevin Sweet and Robert Pilarski and Rachel Pearlman and Kate Shane and Pamela Brock and Westman, {Judith A.} and Lindsay Kipnis and Jilliane Sotelo and Anu Chittenden and Samantha Culver and Stopfer, {Jill E.} and Schneider, {Katherine A.} and Rosalba Sacca and Koeller, {Diane R.} and Shraddha Gaonkar and Erica Vaccari and Sarah Kane and Michalski, {Scott T.} and Shan Yang and Nielsen, {Sarah M.} and Bristow, {Sara L.} and Lincoln, {Stephen E.} and Nussbaum, {Robert L.} and Esplin, {Edward D.}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = may,

day = "1",

doi = "10.3390/cancers14102426",

language = "English",

volume = "14",

journal = "Cancers",

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Espinel, W, Champine, M, Hampel, H, Jeter, J, Sweet, K, Pilarski, R, Pearlman, R , Shane, K , Brock, P, Westman, JA, Kipnis, L, Sotelo, J, Chittenden, A, Culver, S, Stopfer, JE, Schneider, KA, Sacca, R, Koeller, DR, Gaonkar, S, Vaccari, E, Kane, S, Michalski, ST, Yang, S, Nielsen, SM, Bristow, SL, Lincoln, SE, Nussbaum, RL & Esplin, ED 2022, 'Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients', Cancers, vol. 14, no. 10, 2426. https://doi.org/10.3390/cancers14102426

TY - JOUR

T1 - Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients

AU - Espinel, Whitney

AU - Champine, Marjan

AU - Hampel, Heather

AU - Jeter, Joanne

AU - Sweet, Kevin

AU - Pilarski, Robert

AU - Pearlman, Rachel

AU - Shane, Kate

AU - Brock, Pamela

AU - Westman, Judith A.

AU - Kipnis, Lindsay

AU - Sotelo, Jilliane

AU - Chittenden, Anu

AU - Culver, Samantha

AU - Stopfer, Jill E.

AU - Schneider, Katherine A.

AU - Sacca, Rosalba

AU - Koeller, Diane R.

AU - Gaonkar, Shraddha

AU - Vaccari, Erica

AU - Kane, Sarah

AU - Michalski, Scott T.

AU - Yang, Shan

AU - Nielsen, Sarah M.

AU - Bristow, Sara L.

AU - Lincoln, Stephen E.

AU - Nussbaum, Robert L.

AU - Esplin, Edward D.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

AB - Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

KW - DNA damage repair

KW - breast cancer

KW - clinical management

KW - clinical utility

KW - genetic testing

KW - moderate-risk genes

KW - ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=85129820225&partnerID=8YFLogxK

U2 - 10.3390/cancers14102426

DO - 10.3390/cancers14102426

M3 - Article

AN - SCOPUS:85129820225

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 10

M1 - 2426

ER -

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients

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