Invitae Breast and Gyn Cancers Guidelines-Based Panel


Test description

The Invitae Breast and Gyn Cancers Guidelines-Based Panel analyzes 17 genes that are associated with a significantly increased lifetime risk of hereditary breast, ovarian, uterine, fallopian tube, and peritoneal cancer. Some genes on this panel are also associated with an increased risk of other cancer types. All 17 genes on this panel have published management guidelines.

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 (17 genes)


EPCAM: Analysis is limited to deletion/duplication analysis
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
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 multi-gene panels. Depending on the individual’s clinical and family history, a broader panel may be appropriate. Any of these broader panels can be ordered at no additional charge.

  • Hereditary breast and ovarian cancer syndrome (HBOC)
  • Li-Fraumeni syndrome (LFS)
  • Cowden and Cowden-like syndrome
  • Peutz-Jeghers syndrome (PJS)
  • Hereditary diffuse gastric cancer syndrome (HDGC)
  • Lynch syndrome

This test analyzes 17 well established genes that are associated with hereditary breast and gynecologic cancers, specifically of the ovary and uterus. The general population risks for breast, ovarian, and uterine cancer are 12%, 1.3%, and 2.7%, respectively. Like breast cancer, most cases of gynecologic cancers are sporadic and not inherited; however, approximately 5%–10% of breast and gynecologic cancers are hereditary and due to an inherited pathogenic variant.

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 risksGyn cancer risksOther associated cancers
ATM ♀ 17%–52% (PMID 16998505, 1961222, 15928302) ovarian—unknown risk (PMID: 25622547) pancreatic
♂ No known risk
BRCA1 ♀ up to 87% (PMID: 7907678; 12677558) ovarian—up to 54% (PMID: 7907678, 12677558) pancreatic, prostate
♂ 1%–2% (PMID: 18042939, 20587410)
BRCA2 ♀ up to 84% (PMID: 9497246) ovarian—up to 27% (PMID: 9497246) pancreatic, prostate, melanoma
♂ up to 8.9% (PMID: 18042939, 20587410)
BRIP1 possibly elevated (PMID: 21964575, 17033622, 26921362) ovarian—8% (PMID: 21964575) -
CDH1 ♀ 39%–52% (lobular) (PMID: 11729114, 17545690, 25979631) - gastric, colorectal
♂ no known risk
CHEK2 ♀ 25%–39% (PMID: 18172190, 21876083) ovarian—unknown risk (PMID: 24240112; 24879340) colorectal, prostate
♂ possibly elevated (PMID: 18759107)
EPCAM unknown (PMID: 18398828, 23091106) uterine—12%–55% (PMID: 21145788) ovarian—elevated (PMID: 19177550) colorectal, gastric, pancreatic, small bowel, prostate, brain, sebaceous adenoma/carcinoma, urinary tract
MLH1 unknown (PMID: 18398828, 23091106, 26101330) uterine—14%–54% (PMID: 25070057) ovarian—up to 20% (PMID: 25070057) colorectal, gastric, pancreatic, small bowel, prostate, brain, sebaceous adenoma/carcinoma, urinary tract
MSH2 unknown (PMID: 18398828, 23091106) uterine—20%–54% (PMID: 21642682, 23255516, 15236168) ovarian—up to 24% (PMID: 21642682) colorectal, gastric, pancreatic, small bowel, prostate, brain, sebaceous adenoma/carcinoma, urinary tract
MSH6 unknown (PMID: 18398828, 23091106) uterine—up to 71% (PMID: 15236168; 22619739) ovarian—6-8% (PMID: 23091106) colorectal, gastric, pancreatic, small bowel, prostate, brain, urinary tract
PALB2 ♀ up to 58% (PMID: 25099575) ovarian—unknown (PMID: 26075229; 22505525) pancreatic
♂ possibly elevated (PMID: 21285249)
PMS2 unknown (PMID: 18398828, 23091106) uterine—up to 15% (25856668) ovarian—elevated (PMID: 25856668) colorectal, gastric, pancreatic, small bowel, prostate, brain, urinary tract
PTEN ♀ up to 85% (PMID: 22252256) uterine—up to 28% (PMID: 22252256) thyroid, kidney, colorectal, melanoma, brain
♂ unknown (PMID: 11238682)
RAD51C unknown (PMID: 23300655, 22725699) ovarian—6.5% (PMID: 20400964, 21616938, 22538716) -
RAD51D unknown (PMID: 21822267) ovarian—7-10% (PMID: 21822267, 23372765) -
STK11 ♀ 40%–50% (PMID: 20051941) ovarian—18%–20% (PMID: 20051941) uterine—9% (PMID: 20051941) cervical (adenoma malignum)—10% (PMID: 10499464, 21503748, 2678968) colorectal, pancreatic, gastric, small bowel, lung
♂ no known risk
TP53 ♀ up to 79% (PMID: 10864200; 26014290) ovarian—elevated (PMID: 14583457) uterine—elevated (PMID: 20301488) sarcoma, brain, lung, colorectal, gastric, pancreatic
♂ no known risk

All of the genes on this panel have autosomal dominant inheritance for hereditary breast and gynecologic cancers. Several of these genes also result in clinically distinct autosomal recessive conditions:

  • BRCA2, BRIP1 and PALB2 are also associated with Fanconi anemia. There is preliminary evidence supporting an association of RAD51C with Fanconi anemia.
  • MLH1, MSH2, MSH6, and PMS2 are associated with constitutional mismatch repair deficiency (CMMR-D).
  • EPCAM is associated with congenital tufting enteropathy (CTE).
  • ATM is associated with ataxia-telangiectasia.

This panel can be considered for individuals with breast, ovarian, or uterine cancer. Other candidates for testing include those whose clinical and family history is suggestive of a hereditary breast or gynecologic cancer syndrome, including:

  • breast, uterine/endometrial, colon, pancreatic, melanoma, sarcoma, or prostate cancer, particularly if early onset (<50 years)
  • ovarian or fallopian tube cancer
  • male breast cancer
  • a family history of one of these hereditary cancers or other associated cancer types

There are also some common general features suggestive of a family with hereditary cancer syndrome. 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. Aarnio, M. Clinicopathological features and management of cancers in lynch syndrome. Patholog Res Int. 2012; 2012:350309. doi: 10.1155/2012/350309. PMID: 22619739
  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. Bonadona, V, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011; 305(22):2304-10. doi: 10.1001/jama.2011.743. PMID: 21642682
  4. Coulet, F, et al. Germline RAD51C mutations in ovarian cancer susceptibility. Clin. Genet. 2013; 83(4):332-6. doi: 10.1111/j.1399-0004.2012.01917.x. PMID: 22725699
  5. Dowty, JG, et al. Cancer risks for MLH1 and MSH2 mutation carriers. Hum. Mutat. 2013; 34(3):490-7. doi: 10.1002/humu.22262. PMID: 23255516
  6. Easton, DF, et al. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. J. Med. Genet. 2016; :None. PMID: 26921362
  7. Engel, C, et al. Risks of less common cancers in proven mutation carriers with lynch syndrome. J. Clin. Oncol. 2012; 30(35):4409-15. doi: 10.1200/JCO.2012.43.2278. PMID: 23091106
  8. 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
  9. 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
  10. Giardiello, FM, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am. J. Gastroenterol. 2014; 109(8):1159-79. doi: 10.1038/ajg.2014.186. PMID: 25070057
  11. Goodenberger, ML, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet. Med. 2015; :None. doi: 10.1038/gim.2015.27. PMID: 25856668
  12. Hendriks, YM, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004; 127(1):17-25. doi: 10.1053/j.gastro.2004.03.068. PMID: 15236168
  13. Kempers, MJ, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol. 2011; 12(1):49-55. doi: 10.1016/S1470-2045(10)70265-5. PMID: 21145788
  14. Le, Calvez-Kelm, F, et al. RAD51 and breast cancer susceptibility: no evidence for rare variant association in the Breast Cancer Family Registry study. PLoS ONE. 2012; 7(12):e52374. doi: 10.1371/journal.pone.0052374. PMID: 23300655
  15. Loveday, C, et al. Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat. Genet. 2012; 44(5):475-6; author reply 476. doi: 10.1038/ng.2224. PMID: 22538716
  16. Loveday, C, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat. Genet. 2011; 43(9):879-82. doi: 10.1038/ng.893. PMID: 21822267
  17. Meindl, A, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat. Genet. 2010; 42(5):410-4. doi: 10.1038/ng.569. PMID: 20400964
  18. Olivier, M, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003; 63(20):6643-50. PMID: 14583457
  19. Pelttari, LM, et al. RAD51C is a susceptibility gene for ovarian cancer. Hum. Mol. Genet. 2011; 20(16):3278-88. doi: 10.1093/hmg/ddr229. PMID: 21616938
  20. Rafnar, T, et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat. Genet. 2011; 43(11):1104-7. doi: 10.1038/ng.955. PMID: 21964575
  21. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301488
  22. Seal, S, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat. Genet. 2006; 38(11):1239-41. doi: 10.1038/ng1902. PMID: 17033622
  23. 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
  24. Thompson, ER, et al. Analysis of RAD51D in ovarian cancer patients and families with a history of ovarian or breast cancer. PLoS ONE. 2013; 8(1):e54772. doi: 10.1371/journal.pone.0054772. PMID: 23372765

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
BRIP1 NM_032043.2
CDH1 NM_004360.3
CHEK2 NM_007194.3
EPCAM* NM_002354.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
PALB2 NM_024675.3
PMS2 NM_000535.5
PTEN* NM_000314.4
RAD51C NM_058216.2
RAD51D NM_002878.3
STK11 NM_000455.4
TP53* NM_000546.5

EPCAM: Analysis is limited to deletion/duplication analysis
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.