Ordering
  • Test code: 01206
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
Billing
 

Invitae Breast Cancer Guidelines-Based Panel

Test description

The Invitae Breast Cancer Guidelines-Based Panel analyzes eleven well-established genes 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.

Order test

Primary panel (11 genes)

ATM BRCA1 BRCA2 CDH1 CHEK2 NBN NF1 PALB2 PTEN STK11 TP53

Add-on Gene with Emerging Data for Breast Cancer (1 gene)

Invitae offers this gene as an add-on to our guidelines-based breast cancer guidelines panel based on recent clinical updates.

BARD1

Alternative tests to consider

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.

  • Cowden and Cowden-like syndrome
  • hereditary breast and ovarian cancer syndrome (HBOC)
  • hereditary diffuse gastric cancer syndrome (HDGC)
  • Li-Fraumeni syndrome (LFS)
  • neurofibromatosis type 1
  • Peutz-Jeghers syndrome (PJS)

The average woman’s lifetime risk of developing breast cancer is 12%. Although there are a number of other genes associated with hereditary breast cancer, hereditary breast and ovarian cancer syndrome (HBOC), due to pathogenic variants in BRCA1 and BRCA2, accounts for most cases in individuals with a strong family history or an early-onset diagnosis.

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 may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial. For gene-associated cancer risks, see the table below.

GeneBreast cancer risksOther 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

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.

Most of the genes on this panel have autosomal dominant inheritance. Several also have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions, as outlined below:

  • ATM is associated with ataxia-telangiectasia
  • NBN is associated with Nijmegen breakage syndrome
  • BRCA2 and PALB2 are also associated with autosomal recessive Fanconi anemia

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:

  • a breast cancer diagnosis <45 years of age
  • a diagnosis <50 years of age with more than one primary breast cancer diagnosis
  • a diagnosis <60 years of age with triple-negative breast cancer
  • clustering of the following cancers in the family: breast, ovarian, uterine, colon, pancreatic, melanoma, sarcoma, and prostate cancer, particularly if they are early onset (<50 years)
  • male breast cancer
  • breast or ovarian cancer and Ashkenazi Jewish ancestry

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys, both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., male breast cancer)

  1. Ford, D, et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994; 343(8899):692-5. doi: 10.1136/jmg.31.6.504-d. PMID: 7907678
  2. Ford, D, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am. J. Hum. Genet. 1998; 62(3):676-89. doi: 10.1086/301749. PMID: 9497246
  3. Chompret, A, et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br. J. Cancer. 2000; 82(12):1932-7. doi: 10.1054/bjoc.2000.1167. PMID: 10864200
  4. Fackenthal JD, et al. Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet. 2001 Mar;38(3):159-64. PMID: 11238682
  5. Pharoah, PD, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001; 121(6):1348-53. doi: 10.1053/gast.2001.29611. PMID: 11729114
  6. Antoniou, A, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am. J. Hum. Genet. 2003; 72(5):1117-30. doi: 10.1086/375033. PMID: 12677558
  7. Thompson, D, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl. Cancer Inst. 2005; 97(11):813-22. doi: 10.1093/jnci/dji141. PMID: 15928302
  8. Ahmed, M, Rahman, N. ATM and breast cancer susceptibility. Oncogene. 2006; 25(43):5906-11. doi: 10.1038/sj.onc.1209873. PMID: 16998505
  9. Kaurah, P, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007; 297(21):2360-72. doi: 10.1001/jama.297.21.2360. PMID: 17545690
  10. Tai, YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J. Natl. Cancer Inst. 2007; 99(23):1811-4. doi: 10.1093/jnci/djm203. PMID: 18042939
  11. Weischer, M, et al. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J. Clin. Oncol. 2008; 26(4):542-8. doi: 10.1200/JCO.2007.12.5922. PMID: 18172190
  12. van, Lier, MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am. J. Gastroenterol. 2010; 105(6):1258-64; author reply 1265. PMID: 20051941
  13. Evans, DG, et al. Risk of breast cancer in male BRCA2 carriers. J. Med. Genet. 2010; 47(10):710-1. doi: 10.1136/jmg.2009.075176. PMID: 20587410
  14. Casadei S, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011 Mar 15;71(6):2222-9. PMID: 21285249
  15. Cybulski, C, et al. Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J. Clin. Oncol. 2011; 29(28):3747-52. doi: 10.1200/JCO.2010.34.0778. PMID: 21876083
  16. Tan, MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 2012; 18(2):400-7. doi: 10.1158/1078-0432.CCR-11-2283. PMID: 22252256
  17. Antoniou, AC, et al. Breast-cancer risk in families with mutations in PALB2. N. Engl. J. Med. 2014; 371(6):497-506. doi: 10.1056/NEJMoa1400382. PMID: 25099575
  18. van, der, Post, RS, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J. Med. Genet. 2015; 52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. PMID: 25979631
  19. Bougeard, G, et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. J. Clin. Oncol. 2015; 33(21):2345-52. doi: 10.1200/JCO.2014.59.5728. PMID: 26014290
  20. Zhang, B, et al. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol. 2011; 12(5):477-88. PMID: 21514219
  21. Steffen, J, et al. Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int. J. Cancer. 2006; 119(2):472-5. PMID: 16770759
  22. Seminog, OO, Goldacre, MJ. Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study. Br. J. Cancer. 2013; 108(1):193-8. PMID: 23257896
  23. Madanikia, SA, et al. Increased risk of breast cancer in women with NF1. Am. J. Med. Genet. A. 2012; 158A(12):3056-60. PMID: 23165953
  24. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed January 2018.
  25. Swift, M, et al. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N. Engl. J. Med. 1991; 325(26):1831-6. PMID: 1961222

Assay and technical information

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATM NM_000051.3
BARD1 NM_000465.3
BRCA1* NM_007294.3
BRCA2* NM_000059.3
CDH1 NM_004360.3
CHEK2 NM_007194.3
NBN NM_002485.4
NF1 NM_000267.3
PALB2 NM_024675.3
PTEN* NM_000314.4
STK11 NM_000455.4
TP53* NM_000546.5

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.