Breast Cancer Comprehensive Panel

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

Panel Description

Hereditary Breast Cancer
Breast cancer is one of the most common cancers among women and approximately 5 to 10% of breast cancers are hereditary1. Many cases of hereditary breast cancer stem from pathogenic variants in the BRCA1 and BRCA2 genes, which help repair cell damage in the breast and other tissues. Having a pathogenic variant in a gene related to breast cancer predisposition does not guarantee the disease will occur, but it does increase the risk and patients should talk with their care team about tailored cancer screenings.

This panel includes genes with a well-established association with high or moderate risk for breast cancer as well as genes with limited or emerging evidence suggesting an increased risk for breast cancer.

This panel may be appropriate for anyone with a personal or family history of breast cancer. Testing is strongly recommended if your patient or a member of their family has been diagnosed with breast cancer before age 50, triple-negative breast cancer, male breast cancer, or if there have been multiple cases of cancer in a single individual. 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.

Confirming the presence of a pathogenic variant linked to breast cancer helps patients and their care team better monitor risk factors. Knowing the specific variant can lead to more targeted screening and treatment plans.

Genetic testing for hereditary breast cancer can:
  • Establish or confirm a diagnosis
  • Identify risk for other cancers and health conditions
  • Assist in modifying lifestyle changes, including diet and exercise
  • Result in more personalized treatment, which may include increased screening pharmacological treatments, and prophylactic surgeries
  • Inform family members of their own risk factors

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 81433, 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
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 Heterozygous pathogenic variants in the BRCA1 gene are the most common cause of hereditary breast and ovarian cancer syndrome (HBOC). 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 Types B and D1 . PubMed: 12065746, 12677558, 9497246, 17416853, 18042939, 20301425, 22846731; PMC: 2267287
CDH1 Pathogenic heterozygous variants in the CDH1 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 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; 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. PubMed: 26436112, 26328243, 15574463; OMIM: 600814
MSH2 Heterozygous pathogenic variants in MSH2 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; OMIM: 120436
MUTYH Biallelic pathogenic variants in the MUTYH gene cause MUTYH-associated polyposis syndrome (MAP). MUTYH has limited evidence for the increased risk of 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. 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
PTEN Individuals with heterozygous pathogenic PTEN variants are at a significantly increased risk for multiple types of cancers, including breast, thyroid, colorectal, endometrial, renal, and others. Autosomal dominant mutations in PTEN have been associated with a spectrum of disorders sometimes referred to as PTEN hamartoma tumor syndrome. PHTS includes several conditions with overlapping clinical features, including Bannayan-Riley-Ruvalcaba syndrome (BRRS), Cowden syndrome (CWS1), macrocephaly/autism syndrome, and PTEN-related Proteus syndrome (PS). PubMed: 20301661; OMIM: 601728
RAD51C Heterozygous pathogenic variants in RAD51C are associated with an increased risk for ovarian cancer, and possibly breast cancer. Additionally, biallelic pathogenic variants in RAD51C were reported to be associated with Fanconi anemia. PubMed: 22476429, 22538716, 21990120, 2841844
RAD51D Heterozygous pathogenic variants in RAD51D are associated with an increased risk for breast cancer and ovarian cancer. PubMed: 21822267, 26261251, 2841844
STK11 Autosomal dominant pathogenic variants in STK11 have been associated with Peutz-Jeghers syndrome (PJS) which is associated with an increased risk for multiple types of cancer, including breast, ovarian, gastric, colorectal, and pancreatic. PubMed: 15121768, 20301443; OMIM: 175200, 260350
TP53 Heterozygous pathogenic variants in the TP53 gene are associated with Li-Fraumeni syndrome, a condition that increases risk for many types of cancer. PubMed: 20301488, 26014290, 2614290; OMIM: 151623, 191170
XRCC2 Autosomal dominant pathogenic variants in the XRCC2 gene may be associated with an increased risk for breast cancer, but additional research is needed to confirm this association. PubMed: 22464251, 25918678; OMIM: 600375
RAD50 Autosomal dominant pathogenic variants in RAD50 may be associated with a small increased risk for breast cancer, although studies are contradictory. Biallelic pathogenic variants in RAD50 were reported to be associated with Nijmegen breakage syndrome-like disorder (NBSLD) in one individual. PubMed: 19409520, 20301355, 23586058, 26250988, 28418444; OMIM: 613078
CHEK2 Heterozygous pathogenic variants in CHEK2 are associated with approximately a two-fold increased risk for breast cancer, as well as other CHEK2-related cancers. PubMed: 16998506, 18172190, 21876083, 27595995, 15492928, 11719428, 20597917, 21807500, 21876083, 21956126, 23713947, 23296741, 24240112, 24599715, 24879340, 25431674, 11370630, 15951970, 17164383
PALB2 Autosomal dominant pathogenic variants in PALB2 have been associated with an increased risk of some types of cancer, including breast and pancreatic cancer. Biallelic pathogenic variants in PALB2 have been associated with Fanconi anemia of complementation group N (FANCN) . For women, the risk for breast cancer has been estimated to be two to three times greater than the population risk. PubMed: 17200672, 24870022, 17200668, 21285249, 24141787, 25099575; OMIM: 610355
BRIP1 Heterozygous pathogenic germline variants in the BRIP1 gene are associated with an increased risk for ovarian cancer. A possible association with increased risk for breast cancer has also been suggested, although this has not been proven to date. Biallelic mutations in BRIP1 have been associated with Fanconi anemia of complementation group J (FANCJ). PubMed: 24301948, 28085182, 20301575, 26315354, 28418444 ; OMIM: 609054, 605882
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

Appendix

Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int. 2013;2013:747318. doi:10.1155/2013/747318