Breast and Ovarian Cancer Comprehensive Panel

  • Panel Description
  • Test Description
  • CPT Codes
  • Resources
  • Gene Descriptions

Panel Description

Hereditary Breast Cancer
Hereditary Ovarian Cancer
The Breast and Ovarian Cancer Comprehensive Panel examines 36 genes associated with an increased risk for hereditary breast cancer and hereditary ovarian cancer. This test includes both well-established breast and ovarian cancer susceptibility genes, as well as candidate genes with limited evidence of an association with breast and ovarian cancer.

Patients with a personal or family history suggestive of a hereditary breast and ovarian cancer syndrome. Red flags for hereditary breast and ovarian cancer could include onset of cancer prior to the age of 50 years, more than one primary cancer in a single person, and multiple affected people within a family. This test is designed to detect individuals with a germline pathogenic variant, and is not validated to detect mosaicism below the level of 20%. It should not be ordered on tumor tissue.

Patients identified with hereditary breast and ovarian cancer can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Information obtained from candidate gene testing may potentially be helpful in guiding clinical management in the future. Also, if an inherited susceptibility is found, your patient’s family members can be tested to help define their risk. If a pathogenic variant is identified in your patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also be at increased risk.

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
2 - 3 weeks
Call for details
ABRAXAS1, AKT1, ATM, BARD1, BLM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, DICER1, EPCAM, FANCC, FANCM, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PIK3CA, PMS2, PTEN, RAD50, RAD51C, RAD51D, RECQL, SDHB, SDHD, SMARCA4, STK11, TP53, XRCC2 ( 36 genes )
99% at 50x
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
Test results and variant interpretation are based on the proper identification of the submitted specimen and use of correct human reference sequences at the queried loci. In very rare instances, errors may result due to mix-up or co-mingling of specimens. Positive results do not imply that there are no other contributions, genetic or otherwise, to the patient's phenotype, and negative results do not rule out a genetic cause for the indication for testing. Result interpretation is based on the collected information and Alamut annotation available at the time of reporting. This assay is not designed or validated for the detection of mosaicism. DNA alterations in regulatory regions or deep intronic regions (greater than 20bp from an exon) will not be detected by this test. There are technical limitations on the ability of DNA sequencing to detect small insertions and deletions. Our laboratory uses a sensitive detection algorithm, however these types of alterations are not detected as reliably as single nucleotide variants. Rarely, due to systematic chemical, computational, or human error, DNA variants may be missed. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the confounding contribution of pseudogene sequences or other highly-homologous sequences, sometimes these may still interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Deletion/duplication analysis can identify alterations of genomic regions which are a single exon in size. When novel DNA duplications are identified, it is not possible to discern the genomic location or orientation of the duplicated segment, hence the effect of the duplication cannot be predicted. Where deletions are detected, it is not always possible to determine whether the predicted product will remain in-frame or not. Unless otherwise indicated, in regions that have been sequenced by Sanger, deletion/duplication analysis has not been performed. Patients with Bone Marrow Transplants: DNA extracted from cultured fibroblasts should be submitted instead of blood/saliva/buccal samples from individuals who have undergone allogeneic bone marrow transplant and from patients with hematologic malignancy.

Gene Notes
MSH2 Inversion of MSH2 exons 1-7 ("Boland" inversion) is assessed for Lynch Syndrome, Colorectal, Endometrial, and Prostate Cancer Panel testing (for both Focus and Comprehensive Panels) as well as Comprehensive Gastric Cancer Panel testing. Unless otherwise specified, this testing is not performed for other cancer panels, but is available upon request.
PIK3CA Because the vast majority of PIK3CA pathogenic variants arise postzygotic and are thus mosaic, more than one tissue may need to be tested. Failure to detect a PIK3CA pathogenic variant does not exclude a clinical diagnosis of the PIK3CA-associated segmental overgrowth disorders in individuals with suggestive features (PubMed: 23946963).
CPT Code 81405, 81408, 81479

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.
WHY ORDER THIS TEST?

Resources

DescriptionDownload
Hereditary Breast Cancer Information for Patients
Hereditary Ovarian Cancer Information for Patients
Genetic Testing for Hereditary Breast and Ovarian Cancer Webinar

Genetic Testing for Hereditary Cancers Webinar

Gene Descriptions

Gene Reason Reference
AKT1 Heterozygous germline pathogenic variants in AKT1 have been suggested in association with Cowden and Cowden-like syndrome. Cowden syndrome has an increased risk for multiple types of cancers, including breast, thyroid, colorectal, endometrial, renal, and others. PMID: 23246288; OMIM 164730
ATM Heterozygous pathogenic variants in ATM are associated with an increased risk for breast and pancreatic cancer. Additionally, biallelic pathogenic variants in ATM have been associated with ataxia-telangiectasia. PubMed: 15928302, 22585167, 20301790, 28418444; OMIM: 607585
BARD1 Heterozygous pathogenic variants in the BARD1 gene raise an individual’s risk of developing breast cancer in their lifetime. PubMed:23586058, 28418444; OMIM: 114480
BLM Biallelic pathogenic variants in the BLM gene cause Bloom's syndrome. Individuals with Bloom's syndrome are at a greatly increased risk for many types of cancer, including leukemia and lymphoma. Cancers often occur at younger than typical ages. Patients with Bloom's syndrome are hypersensitive to some forms of cancer treatment. Additionally, carriers of heterozygous pathogenic BLM variants may be at a small increased risk for breast cancer, as well as others (low/moderate penetrance). However, additional studies are needed to confirm an association. PubMed: 20301572, 19432957, 23404160, 24733792, 26358404; OMIM: 210900
BRCA1 Autosomal dominant pathogenic variants in the BRCA1 gene are the most common cause of hereditary breast and ovarian cancer syndrome (HBOC), which includes up to a 63% lifetime risk for ovarian cancer. PubMed: 9497246, 12677558, 17416853, 20301425, 22846731
BRCA2 Autosomal dominant mutations in the BRCA2 gene are implicated in the hereditary breast and ovarian cancer syndrome (HBOC). Additionally, biallelic mutations in BRCA2 gene are associated with autosomal recessive Fanconi anemia Type D1 . PubMed: 12065746, 12677558, 9497246, 17416853, 18042939, 20301425, 22846731; PMC: 2267287
CDH1 Pathogenic heterozygous variants in the CDH1 (E-Cadherin) gene are associated with an increased risk for gastric and lobular breast cancer. PubMed: 11729114, 20301318; OMIM: 192090
FANCC Biallelic pathogenic variants in FANCC are responsible for approximately 14% of Fanconi Anemia cases. Studies examining cancer risk for heterozygous carriers of pathogenic FANCC variants are contradictory, and additional research is needed. PubMed: 20301575, 12750283, 14726700, 26778106; OMIM: 613899, 227645
MSH6 Heterozygous pathogenic variants in MSH6 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). MSH6 is associated with an increased risk for breast and ovarian cancer. PubMed: 25963852, 20301390, 22692065, 23530095, 2442514, 24434690, 23462293, 21642682; OMIM: 120436
EPCAM Heterozygous pathogenic variants in the EPCAM gene cause Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, which is associated with an increased risk for ovarian cancer and a possible increased risk for breast cancer. PubMed: 20301390, 23462293, 23530095, 24434690, 24425144, 25963852, 24138022, 23730225; OMIM 613244
MLH1 While heterozygous pathogenic variants in MLH1 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065, 25963852, 20442441; 23530095, 24434690, 23462293; OMIM: 120436
MRE11 Autosomal dominant pathogenic variants in the MRE11 gene, also known as MRE11A, have been associated with a predisposition to breast cancer . Biallelic mutations in the MRE11A gene are associated with MRE11 deficiency, an ataxia telangiectasia-like disorder. At this time, an association with ovarian cancer has not been found; additional research is needed. PubMed: 26436112, 26328243, 15574463; OMIM: 600814
MUTYH Biallelic pathogenic variants in the MUTYH gene cause MUTYH-associated polyposis syndrome (MAP). Heterozygous pathogenic variants in the MUTYH have been reported with an elevated risk for ovarian cancer and breast cancer. More research is needed. PubMed: 16492921, 19394335, 23035301, 23507534
NBN Heterozygous pathogenic variants in NBN (also known as NBS1) have been associated with a number of malignancies including melanoma, non-Hodkins lymphoma, medulloblastoma, and colorectal, prostate, and breast cancers . Other studies have shown possible associations with aplastic anemia and acute lymphoblastic leukemia. Biallelic pathogenic variants in NBN have been associated with Nijmegen Breakage syndrome (NBS). Individuals with NBS generally have progressive intellectual disability, growth restriction, and immunodeficiency; and are at an increased risk for a variety of cancers, including lymphoma, glioma, and medulloblastoma. PubMed: 14973119, 15185344, 16474176, 16770759, 18079974, 19908051, 21514219,15338273,11325820, 20301355; OMIM: 609135, 251260
NF1 Autosomal dominant pathogenic variants in NF1 are associated with an increased risk for breast cancer and also cause Neurofibromatosis Type 1. More research is needed if it is associated with an increased risk for ovarian cancer. PubMed: 19449407, 10588837, 23598713, 17636453, 20301288, 9639526, 27787920, 16861979; OMIM: 613113
NTHL1 Biallelic pathogenic variants in the base excision repair gene NTHL1 have been associated with familial adenomatous polyposis-3 (FAP3) which is also referred to as NTHL1-associated polyposis (NAP). Biallelic pathogenic variants NTHL1 are also associated with breast cancer. PubMed: 28331556, 26431160, 30753826; OMIM: 602656
ABRAXAS1 The ABRAXAS (FAM175A) gene is involved in the DNA double-strand break (DSB) repair pathway. Variants in ABRAXAS may impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation (PubMed: 17525340, 22357538, 25105795; OMIM: 611143). The loss-of-function ABRAXAS germline variant was also identified in ovarian carcinomas (PubMed: 24240112). Further studies may be necessary to clarify these findings. PubMed: 17525340, 22357538, 25105795, 22357538, 24240112; OMIM: 611143