Abstract
Real-world clinical and genomic analysis of patients with a personal or family history of cancer undergoing germline testing for BRCA1 and BRCA2.
Author
person
Rebecca A. Previs
Labcorp Oncology | Duke University Medical Center, Duke Cancer Institute, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Durham, NC
info_outline
Rebecca A. Previs, Heidi Chwan Ko, Zachary D. Wallen, Kyle C. Strickland, Mary K. Nesline, Dagny Noeth, Melissa Hayden, Sabrina Gardner, Ruth A. Heim, Taylor J. Jensen, Prasanth Reddy, Eric A Severson, Shakti Ramkissoon
Full text
Authors
person
Rebecca A. Previs
Labcorp Oncology | Duke University Medical Center, Duke Cancer Institute, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Durham, NC
info_outline
Rebecca A. Previs, Heidi Chwan Ko, Zachary D. Wallen, Kyle C. Strickland, Mary K. Nesline, Dagny Noeth, Melissa Hayden, Sabrina Gardner, Ruth A. Heim, Taylor J. Jensen, Prasanth Reddy, Eric A Severson, Shakti Ramkissoon
Organizations
Labcorp Oncology | Duke University Medical Center, Duke Cancer Institute, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Durham, NC, Labcorp Oncology, Durham, NC, Labcorp Oncology | Duke University Medical Center, Duke Cancer Institute, Department of Pathology, Durham, NC, Labcorp, Research Triangle Park, NC, Labcorp Oncology | Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Durham, NC
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Labcorp
Background:
Germline genetic testing for hereditary cancer syndromes is essential to the management of patients with cancer, providing information with both therapeutic implications and guidance for preventative strategies for patients and at-risk family members.
BRCA1
and
BRCA2
are the most common genes with deleterious mutations associated with increased risk of developing hereditary breast, ovarian, prostate and pancreatic cancers. The objective of this study was to explore the prevalence of germline
BRCA1
and
BRCA2
mutations in individuals with known cancer compared to those with only a family history of cancer in a real-world patient population.
Methods:
Real-world clinical and genomic data were reviewed for 12,270 consecutive individuals referred to a clinical laboratory for
BRCA1
and
BRCA2
sequencing and copy number variant analysis. Clinical data were ascertained from testing requisition forms completed by healthcare providers. Germline variants in
BRCA1
and
BRCA2
were identified by next-generation sequencing. The incidence of pathogenic and likely pathogenic variants (PVs) were calculated for each gene, patient cohort and four common cancer types: breast, ovarian, prostate, and pancreatic. Statistical analysis was performed using chi squared and Fisher’s exact tests.
Results:
Among the 12,270 individuals referred for germline testing for
BRCA1
and
BRCA2,
the majority were female (11,233, 91.5%). A large proportion of patients (9271, 75.6%) had a family history of breast, ovarian, pancreatic or prostate cancer. A total of 2506 patients (20.4%) had a personal history of one of these cancers. For 493 (4.0%), the exact indication for testing was unknown. The median age of patients with a personal history of cancer was 62 years (range: 18 to 95), significantly higher than the median age of patients with a family history of cancer (41 years, range: 3 to 89) (p < 0.0001). For the 2506 patients who reported a personal history of cancer, the most common cancer was breast (1919, 76.6%) followed by prostate (261, 10.4%), ovarian (253, 10.1%), and pancreatic (107, 4.3%). Testing identified 561 PVs, 243 in
BRCA1
and 318 in
BRCA2
. PVs were identified significantly more often in patients with a family history compared to a personal history of breast cancer (4.4% vs 4.2%; p = 0.009) and pancreatic cancer (4.8% vs 2.8%; p = 0.03).
Conclusions:
Our data show that the prevalence of pathogenic or likely pathogenic variants in
BRCA1
and
BRCA2
is higher in individuals with a family history of breast and pancreatic cancers than in individuals with a personal history of these cancers
.
These results corroborate the utility of germline testing in identifying individuals with an inherited predisposition to cancer regardless of having a personal history of cancer, in a real-world setting.
5 organizations
2 drugs
2 targets
Organization
Labcorp Oncology, Duke University Medical Center, Duke Cancer Institute, Department of Pathology, Durham, NCOrganization
Duke University Medical CenterOrganization
Wake Forest Comprehensive Cancer CenterOrganization
Research Triangle Park, NCDrug
BRCA1Drug
BRCA2Target
BRCA1Target
BRCA2