The Invitae Breast Cancer Guidelines-Based Panel analyzes eleven well-established genes that are associated with hereditary breast cancer and an increased risk of other cancers. This panel includes genes for which the National Comprehensive Cancer Network® (NCCN) currently recommends enhanced breast cancer screening (i.e., breast MRI) and possible preventive measures. Each of these eleven genes has published management guidelines that differ from the general population screening and management recommendations.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
ATM BRCA1 BRCA2 CDH1 CHEK2 NBN NF1 PALB2 PTEN STK11 TP53
ATM BRCA1 BRCA2 CDH1 CHEK2 NBN NF1 PALB2 PTEN STK11 TP53
These genes can also be ordered as part of broader, cross-cancer, multi-gene panels. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
Approximately 1 in 8 women (12%) will develop breast cancer in her lifetime. Most breast cancers are sporadic, but approximately 5%–10% of cases are hereditary and due to an inherited pathogenic variant in a susceptibility gene. The nine genes on this panel are the most well-established breast cancer susceptibility genes, with specific management guidelines to aid in early detection and prevention.
The Invitae Breast Cancer Guidelines-Based Panel includes the list of genes for which the National Comprehensive Cancer Network® (NCCN) currently recommends enhanced breast cancer screening (i.e., breast MRI) and possible preventive measures. Adherence to these guidelines may result in risk-reduction and early diagnosis, increasing the chances of successful treatment and survival.
Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant. For gene-associated cancer risks, see the table below.
|Gene||Breast cancer risks||Other associated cancers|
|ATM||♀ 17%–52% (PMID: 16998505, 1961222, 15928302) ♂ no known risk||pancreatic|
|BRCA1||♀ up to 87% (PMID: 7907678; 12677558)||ovarian, pancreatic, prostate|
|♂ 1%–2% (PMID: 18042939, 20587410)|
|BRCA2||♀ Up to 84% (PMID 9497246)||ovarian, pancreatic, prostate, melanoma|
|♂ Up to 8.9% (PMID: 18042939, 20587410)|
|CDH1||♀ 39%–52% (lobular) (PMID: 11729114, 17545690, 25979631) ♂ no known risk||gastric, colorectal|
|CHEK2||♀ 25%–39% (PMID: 18172190, 21876083) ♂ possibly elevated (PMID: 21956126)||colorectal, prostate|
|NBN||up to 30% (PMID: 21514219, 16770759)||prostate|
|NF1||elevated (PMID: 23257896, 23165953)||pancreatic, gastrointestinal stromal tumors (GIST), malignant peripheral nerve sheath tumors (MPNST), pheochromocytoma, myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML)|
|PALB2||♀ up to 58% (PMID: 25099575) ♂ possibly elevated (PMID: 21285249)||pancreatic|
|PTEN||♀ up to 85% (PMID: 22252256) ♂ unknown (PMID: 11238682)||thyroid, uterine, kidney, colorectal, melanoma, brain|
|STK11||♀ 40%–50% (PMID: 20051941) ♂ no known risk||colorectal, pancreatic, ovarian, uterine, gastric, small bowel, lung|
|TP53||♀ up to 79% (PMID: 10864200, 26014290) ♂ no known risk||sarcoma, brain, lung, ovarian, uterine, colorectal, gastric, pancreatic|
All of the genes on this panel have autosomal dominant inheritance for hereditary breast cancer. The BRCA2 and PALB2 genes are also associated with autosomal recessive Fanconi anemia. The ATM gene is associated with autosomal recessive ataxia-telangiectasia. The NBN gene is associated with autosomal recessive Nijmegen breakage syndrome.
This panel comprises hereditary breast cancer genes for which there are established medical management guidelines. It may be considered for individuals with a personal and/or family history of:
There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:
For the most current management recommendations, please see the NCCN guidelines at:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.