• Test code: 01204
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Breast and Gyn Cancers Guidelines-Based Panel

Test description

The Invitae Breast and Gyn Cancers Guidelines-Based Panel analyzes genes 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. This panel includes genes for which the National Comprehensive Cancer Network® (NCCN) currently recommends enhanced surveillance and possible preventive measures. Each of these 19 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.

PTEN: Deletion/duplication analysis covers the promoter region.

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Primary panel (19 genes)


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

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


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.

  • Cowden and Cowden-like syndrome
  • hereditary breast and ovarian cancer syndrome (HBOC)
  • hereditary diffuse gastric cancer syndrome (HDGC)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome – also known as hereditary non-polyposis colorectal cancer (HNPCC)
  • neurofibromatosis type 1 (NF1)
  • Peutz-Jeghers syndrome (PJS)

This test analyzes 19 well-established genes 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.

The 19 genes on this panel are associated with a significantly increased risk of breast and/or gynecologic cancers. The National Comprehensive Cancer Network® (NCCN) has developed guidelines for the screening and management of individuals with pathogenic variants in each of these genes. 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 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
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) 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

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

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).
  • ATM is associated with ataxia-telangiectasia.
  • NBN is associated with Nijmegen breakage syndrome.

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. 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
  2. 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
  3. Loveday, C, et al. Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat. Genet. 2012; 44(5):475-6; author reply 476. PMID: 22538716
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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. PMID: 23300655
  12. 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
  13. Pelttari, LM, et al. RAD51C is a susceptibility gene for ovarian cancer. Hum. Mol. Genet. 2011; 20(16):3278-88. PMID: 21616938
  14. 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. PMID: 15236168
  15. Goodenberger, ML, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet. Med. 2015; :None. doi: 10.1038/gim.2015.27. PMID: 25856668
  16. 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
  17. 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
  18. 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. PMID: 20400964
  19. 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
  20. Rafnar, T, et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat. Genet. 2011; 43(11):1104-7. PMID: 21964575
  21. 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
  22. Loveday, C, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat. Genet. 2011; 43(9):879-82. PMID: 21822267
  23. 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. PMID: 17033622
  24. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle. PMID: 20301488
  25. Aarnio, M. Clinicopathological features and management of cancers in lynch syndrome. Patholog Res Int. 2012; 2012:350309. doi: 10.1155/2012/350309. PMID: 22619739
  26. 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
  27. 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. PMID: 23372765
  28. 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

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
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
NBN NM_002485.4
NF1* NM_000267.3
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

ATM: Sequencing analysis for exons 6, 24, 43 includes only cds +/- 10 bp.
BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
EPCAM: Sequencing analysis is not offered for this gene.
MLH1: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 12 includes only cds +/- 10 bp.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation). Sequencing analysis for exons 2, 5 includes only cds +/- 10 bp.
MSH6: Sequencing analysis for exons 7, 10 includes only cds +/- 10 bp.
NF1: Sequencing analysis for exons 2, 7, 25, 41, 48 includes only cds +/- 10 bp.
PMS2: Sequencing analysis for exons 7 includes only cds +/- 10 bp.
PTEN: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 8 includes only cds +/- 10 bp.
TP53: Deletion/duplication analysis covers the promoter region.