Invitae Breast and Gyn Cancers Panel


Test description

The Invitae Breast and Gyn Cancers Panel analyzes genes that are associated with hereditary breast, ovarian, and uterine cancers. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for women’s breast and gynecologic cancers.

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 (23 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.

Add-on preliminary-evidence genes (12 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

These genes can also be ordered as part a broader, cross-cancer, multi-gene panel. Depending on the individual’s clinical and family history, this broader panel may be appropriate. This broader panel can be ordered at no additional charge.

  • Cowden and Cowden-like syndrome
  • DICER1 syndrome
  • Hereditary breast and ovarian cancer syndrome (HBOC)
  • Hereditary diffuse gastric cancer (HDGC)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome
  • Neurofibromatosis type 1 (NF1)
  • Peutz-Jeghers syndrome (PJS)

This test analyzes genes that are associated with hereditary breast, ovarian, and uterine cancers. Gynecologic cancers include those 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 due to an inherited predisposition.

Pathogenic mutations in BRCA1 or BRCA2 account for the majority of hereditary breast and ovarian cancer cases in individuals with a strong family history or an early-onset diagnosis.
Lynch syndrome is the most common inherited cause of uterine cancer and is also a common genetic cause of ovarian and colon cancer.

The other genes on this panel are associated with different hereditary cancer syndromes that predispose individuals to breast and/or gynecologic cancers. Their inclusion is expected to increase the clinical sensitivity of this test.

Individuals with a pathogenic variant in one of these genes have a significantly increased risk of developing cancer, many of which may be difficult both to detect and to treat. Identifying those at high risk enables implementation of additional screening, surveillance, and interventions. These efforts 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 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, download our Cancer risk poster.

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

  • BRCA2, BRIP1, FANCC, PALB2, and RAD51C are associated with Fanconi anemia.
  • ATM and MRE11A are associated with ataxia-telangiectasia and ataxia-telangiectasia-like disorder (ATLD), respectively.
  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency (CMMR-D).
  • EPCAM is associated with congenital tufting enteropathy (CTE).
  • NBN and RAD50 are associated with Nijmegen breakage syndrome and Nijmegen breakage syndrome-like disorder (NBSLD), respectively.

This panel may be considered for individuals with:

  • breast, ovarian and/or uterine cancer, particularly if early-onset (<50 years of age)
  • multiple primary cancers when at least one is ovarian, uterine, or fallopian tube cancer
  • a family history of one of these hereditary cancers or other associated cancer types

There are also some common general features that are 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)

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  3. American Cancer Society, Lifetime Risks of Developing Various Cancers. Accessed June 2015.
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  23. Goodenberger, ML, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet. Med. 2015; :None. doi: 10.1038/gim.2015.27. PMID: 25856668
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  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. Madanikia, SA, et al. Increased risk of breast cancer in women with NF1. Am. J. Med. Genet. A. 2012; 158A(12):3056-60. doi: 10.1002/ajmg.a.35550. PMID: 23165953
  33. 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
  34. Minion, LE, et al. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2. Gynecol. Oncol. 2015; 137(1):86-92. doi: 10.1016/j.ygyno.2015.01.537. PMID: 25622547
  35. National Comprehensive Cancer Institute, Who should consider genetic testing for cancer risk? Accessed September 2015.
  36. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Breast and Ovarian Management Based on Genetic Test Results. Accessed September 2015.
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  38. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  39. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Guidelines for Breast and/or Ovarian Genetic Risk Assessment. Accessed September 2015.
  40. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Management Guidelines for HBOC. Accessed September 2015.
  41. 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
  42. Ow, GS, et al. Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures. Cell Cycle. 2014; 13(14):2262-80. doi: 10.4161/cc.29271. PMID: 24879340
  43. Park, DJ, et al. Rare mutations in RINT1 predispose carriers to breast and Lynch syndrome-spectrum cancers. Cancer Discov. 2014; 4(7):804-15. doi: 10.1158/2159-8290.CD-14-0212. PMID: 25050558
  44. 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
  45. Pennington, KP, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin. Cancer Res. 2014; 20(3):764-75. doi: 10.1158/1078-0432.CCR-13-2287. PMID: 24240112
  46. 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
  47. Poumpouridou, N, Kroupis, C. Hereditary breast cancer: beyond BRCA genetic analysis; PALB2 emerges. Clin. Chem. Lab. Med. 2012; 50(3):423-34. doi: 10.1515/cclm-2011-0840. PMID: 22505525
  48. 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
  49. Ramos, P, et al. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4. Nat. Genet. 2014; 46(5):427-9. doi: 10.1038/ng.2928. PMID: 24658001
  50. Ramus, SJ, et al. Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. J. Natl. Cancer Inst. 2015; 107(11):None. PMID: 26315354
  51. Ramus, SJ, et al. Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. J. Natl. Cancer Inst. 2015; 107(11):None. doi: 10.1093/jnci/djv214.
  52. Ratajska, M, et al. Cancer predisposing BARD1 mutations in breast-ovarian cancer families. Breast Cancer Res. Treat. 2012; 131(1):89-97. doi: 10.1007/s10549-011-1403-8. PMID: 21344236
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  54. 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
  55. 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. doi: 10.1038/bjc.2012.535. PMID: 23257896
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  58. 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
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  60. 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
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  62. Walsh, T, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc. Natl. Acad. Sci. U.S.A. 2011; 108(44):18032-7. doi: 10.1073/pnas.1115052108. PMID: 22006311
  63. Watson, P, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int. J. Cancer. 2008; 123(2):444-9. doi: 10.1002/ijc.23508. PMID: 18398828
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  65. Witkowski, L, et al. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat. Genet. 2014; 46(5):438-43. doi: 10.1038/ng.2931. PMID: 24658002
  66. Wu, Y, et al. DICER1 mutations in a patient with an ovarian Sertoli-Leydig tumor, well-differentiated fetal adenocarcinoma of the lung, and familial multinodular goiter. Eur J Med Genet. 2014; 57(11-12):621-5. doi: 10.1016/j.ejmg.2014.09.008. PMID: 25451712
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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
AKT1 NM_005163.2
ATM NM_000051.3
BARD1 NM_000465.3
BRCA1 NM_007294.3
BRCA2 NM_000059.3
BRIP1 NM_032043.2
CDC73 NM_024529.4
CDH1 NM_004360.3
CHEK2 NM_007194.3
DICER1 NM_177438.2
EPCAM* NM_002354.2
FAM175A NM_139076.2
FANCC NM_000136.2
MLH1* NM_000249.3
MRE11A NM_005591.3
MSH2* NM_000251.2
MSH6 NM_000179.2
MUTYH NM_001128425.1
NBN NM_002485.4
NF1 NM_000267.3
PALB2 NM_024675.3
PIK3CA NM_006218.2
PMS2 NM_000535.5
POLD1 NM_002691.3
PTEN* NM_000314.4
RAD50 NM_005732.3
RAD51C NM_058216.2
RAD51D NM_002878.3
RINT1 NM_021930.4
SDHB NM_003000.2
SDHD NM_003002.3
SMARCA4 NM_001128849.1
STK11 NM_000455.4
TP53* NM_000546.5
XRCC2 NM_005431.1

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.