Limitations of direct-to-consumer (DTC) genetic testing for hereditary breast and ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10515-10515
Author(s):  
Neelam Vijay Desai ◽  
Elizabeth Dominic Barrows ◽  
Sarah M. Nielsen ◽  
Kathryn E. Hatchell ◽  
Edward D. Esplin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Indication ◽  
Ovarian Cancer Risk ◽  
Cancer Genes ◽  
Primary Analysis ◽  
Risk Genes ◽  
Group 3 ◽  
Group 5

10515 Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant (PLPV) in BRCA1/2 or other cancer-risk genes. Methods: Multi-panel genetic testing was performed in 348,692 individuals for a clinical indication of hereditary breast/ovarian cancer (Clinical cohort) and 7,636 self-referred ostensibly healthy individuals (Healthy cohort) by a clinical testing laboratory. The primary analysis evaluated PLPVs for Group 1 genes: BRCA1/2 AJ founder variants and Group 2: full sequence BRCA1/2. Secondary analyses assessed PLPVs in Group 3: high-risk breast cancer genes ( BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53), Group 4: all breast or ovarian cancer-risk genes (Group 3 genes plus ATM, BARD1, BRIP1, truncating CHEK2, EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D) and Group 5: 41 cancer-risk genes; these analyses were limited to participants who tested for all 41 genes. Potentially mosaic variants were excluded. Results: Table illustrates PLPVs found in both cohorts. The BRCA1/2 AJ founder variants account for only ̃11% (1513/13,987) and ̃30% (19/64) of the BRCA PLPVs in the Clinical and Healthy cohorts, respectively. Even among AJ individuals, testing only for the 3 founder variants will miss ̃10% (52/513) of all BRCA1/2 PLPVs. Evaluating only the BRCA AJ founder variants missed a higher percentage of PLPVs in other cancer-risk genes. Conclusions: The 3 BRCA1/2 AJ founder variants analyzed by DTC testing account for a small fraction of PLPVs in cancer-risk genes in the general population, and miss 10% of BRCA PLPVs even among AJ individuals. Greater public education is needed to dispel the misconception that DTC tests are equivalent to clinical assessment and comprehensive genetic testing. PLPVs identified in Clinical and Healthy Cohorts.[Table: see text]

scholarly journals Population-Based, Risk-Stratified Genetic Testing for Ovarian Cancer Risk: A Focus Group Study

2013 ◽  
Vol 16 (4) ◽  
pp. 184-191 ◽  
Author(s):  
S.F. Meisel ◽  
L. Side ◽  
L. Fraser ◽  
S. Gessler ◽  
J. Wardle ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Focus Group ◽  
Cancer Risk ◽  
Population Based ◽  
Ovarian Cancer Risk ◽  
Focus Group Study

Pathogenic Variants in BRIP1, RAD51C, and RAD51D Identified with Multi-Gene Panel Testing for Hereditary Cancers

2020 ◽  
Author(s):  
Shelly Cummings ◽  
Susana San Roman ◽  
Jennifer Saam ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Cancer Diagnosis ◽  
Fold Increase ◽  
Ovarian Cancer Risk ◽  
Risk Genes ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of

Abstract Background: Professional society guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) for women with pathogenic variants (PVs) in ovarian cancer-risk genes. Personalization of that intervention is based on gene-specific phenotypes; however, the age of ovarian cancer diagnosis in women with PVs in moderate penetrance ovarian cancer-risk genes is not well characterized. Women who had hereditary cancer panel testing from September 2013-May 2019 were included (N=631,950). Clinical/demographic information was compared for women with a PV in BRIP1, RAD51C, or RAD51D versus in BRCA1 or BRCA2. Results: PVs in BRIP1, RAD51C, or RAD51D were identified in 0.5% of all tested women but in 1.6% of women with a history of ovarian cancer (~3-fold increase). PVs in BRCA1 or BRCA2 were identified in 2.4% of all tested women but in 6.1% of women with a history of ovarian cancer (~2.5-fold increase). The proportion of women with a personal or family history of ovarian cancer was similar among women with a PV in BRIP1, RAD51C, RAD51D, BRCA1, or BRCA2. The median age at ovarian cancer diagnosis was 53 years in BRCA1, 59 years for BRCA2, 65 years for BRIP1, 62 years for RAD51C, and 57 years for RAD51D.Conclusions: These data reinforce the importance of identifying PVs in moderate penetrance ovarian cancer-risk genes. The age at ovarian cancer diagnosis was older for women with PVs in BRIP1, RAD51C, or RAD51D, suggesting that it is safe to delay RRSO until age 45-50 in RAD51D PV carriers and possibly, until age 50-55 in BRIP and RAD51C PV carriers.

scholarly journals Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shelly Cummings ◽  
Susana San Roman ◽  
Jennifer Saam ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Cancer Diagnosis ◽  
Fold Increase ◽  
Ovarian Cancer Risk ◽  
Risk Genes ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of

Abstract Background Professional society guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) for women with pathogenic variants (PVs) in ovarian cancer-risk genes. Personalization of that intervention is based on gene-specific phenotypes; however, the age of ovarian cancer diagnosis in women with PVs in moderate penetrance ovarian cancer-risk genes is not well characterized. Women who had hereditary cancer panel testing from September 2013–May 2019 were included (N = 631,950). Clinical/demographic information was compared for women with a PV in BRIP1, RAD51C, or RAD51D versus in BRCA1 or BRCA2. Results PVs in BRIP1, RAD51C, or RAD51D were identified in 0.5% of all tested women but in 1.6% of women with a history of ovarian cancer (~ 3-fold increase). PVs in BRCA1 or BRCA2 were identified in 2.4% of all tested women but in 6.1% of women with a history of ovarian cancer (~ 2.5-fold increase). The proportion of women with a personal or family history of ovarian cancer was similar among women with a PV in BRIP1, RAD51C, RAD51D, BRCA1, or BRCA2. The median age at ovarian cancer diagnosis was 53 years for BRCA1, 59 years for BRCA2, 65 years for BRIP1, 62 years for RAD51C, and 57 years for RAD51D. Conclusions These data reinforce the importance of identifying PVs in moderate penetrance ovarian cancer-risk genes. The age at ovarian cancer diagnosis was older for women with PVs in BRIP1, RAD51C, or RAD51D, suggesting that it is safe to delay RRSO until age 45–50 in RAD51D PV carriers and possibly until age 50–55 in BRIP and RAD51C PV carriers.

Comprehensive genetic testing: The next generation in an ovarian cancer risk assessment clinic

2015 ◽  
Vol 137 ◽  
pp. 102-103
Author(s):  
C.L. Walters Haygood ◽  
K.F. Handley ◽  
M.B. Farmer ◽  
R.D. Alvarez ◽  
C.A. Leath ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Cancer Risk Assessment ◽  
Ovarian Cancer Risk ◽  
Next Generation ◽  
Assessment Clinic
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