Invitae Breast Cancer Guidelines-Based Panel


Test description

The Invitae Breast Cancer Guidelines-Based Panel analyzes nine well-established genes that are associated with hereditary breast cancer and an increased risk of other cancers. This panel differs from the Invitae Breast Cancer High-Risk Panel by the addition of two genes: ATM and CHEK2. The addition of ATM and CHEK2 completes 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. Each of these nine 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.

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Primary panel (9 genes)


PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.

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)
  • Peutz-Jeghers syndrome (PJS)

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.

Guidelines are available for the screening and management of individuals with pathogenic variants in each of these genes.

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.

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
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.

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. Ahmed, M, Rahman, N. ATM and breast cancer susceptibility. Oncogene. 2006; 25(43):5906-11. doi: 10.1038/sj.onc.1209873. PMID: 16998505
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. Accessed September 2015.
  14. 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
  15. 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
  16. Swift, M, et al. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N. Engl. J. Med. 1991; 325(26):1831-6. doi: 10.1056/NEJM199112263252602.
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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. doi: 10.1038/ajg.2009.725. PMID: 20051941
  22. 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

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, 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
ATM NM_000051.3
BRCA1 NM_007294.3
BRCA2 NM_000059.3
CDH1 NM_004360.3
CHEK2 NM_007194.3
PALB2 NM_024675.3
PTEN* NM_000314.4
STK11 NM_000455.4
TP53* NM_000546.5

PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.