Medical Policy

 

Subject: Genetic Testing for Breast and/or Ovarian Cancer Syndrome
Document #: GENE.00029 Publish Date:    12/27/2017
Status: Revised Last Review Date:    05/04/2017

Description/Scope

This document addresses genetic testing for individuals who are at higher than average risk for the development of breast and/or ovarian cancer.  Genetic tests addressed in this document include, but are not limited to the following:

Note: For additional information on genetic testing for malignant conditions, please refer to:

Position Statement

Medically Necessary:

BRCA1 and BRCA2

  1. Genetic testing to detect BRCA1 and/or BRCA gene mutations in individuals who are at higher than average risk for the development of breast and/or ovarian cancer is considered medically necessary when any one of the criteria in A through D and all of the criteria in E are met. 
    1. For individuals from a family with a known deleterious BRCA1/BRCA2 mutation,: or
    2. For individuals with a personal history of cancer and any one of criteria 1 through 13 are met:
      1. The individual was diagnosed with breast cancer prior to age 50; or
      2. The individual has a history of breast cancer diagnosed at any age and at least 1 first-, second- or third-degree relative with breast cancer diagnosed at age 50 years or less; or
      3. The individual has multiple primary breast cancers (bilateral [contralateral] disease or two or more separate ipsilateral primary tumors either synchronously or asynchronously); or
      4. The individual is a male with breast cancer; or
      5. The individual has triple negative breast cancer diagnosed at age 60 or less; or
      6. The individual has a history of breast cancer and a first-, second- or third-degree male relative with breast cancer; or
      7. The individual has a history of breast cancer and 2 or more first-, second- or third-degree relatives on the same side of the family with pancreatic cancer; or
      8. The individual has a history of ovarian, fallopian tube or primary peritoneal cancer; or
      9. The individual has a history of pancreatic cancer and a first-, second-, or third-degree relative with breast cancer (diagnosed at or prior to 50 years of age) and/or ovarian, fallopian tube, primary peritoneal or pancreatic cancer at any age; or
      10. The individual is of Ashkenazi Jewish descent and has a history of pancreatic cancer; or
      11. The individual has a history of breast cancer and at least 2 or more first-, second- or third-degree relatives on the same side of the family with breast cancer; or
      12. The individual has a history of breast cancer and at least 1 first-, second- or third-degree relative with ovarian, fallopian tube, or primary peritoneal cancer; or
      13. The individual has a history of breast cancer and belongs to a population at risk for specific mutations due to ethnic or racial background (African American, Ashkenazi Jewish, Icelandic, Swedish, Hungarian or Dutch descent); or
    3. For individuals with a family (no personal) history of cancer when they have a relative who would meet any one of criteria 1 through 13, but that relative is not available for testing:
      1. The individual for whom the test is requested, has a first- or second-degree relative who had breast cancer diagnosed prior to age 50; or
      2. The individual for whom the test is requested, has a first- or second-degree relative with breast cancer diagnosed at any age and that relative has at least 1 first-, second- or third-degree relative with breast cancer diagnosed at age 50 years or less; or
      3. The individual for whom the test is requested, has a first- or second-degree relative who had multiple primary breast cancers (bilateral [contralateral] disease or two or more separate ipsilateral primary tumors either synchronously or asynchronously); or
      4. The individual for whom the test is requested, has a first- or second-degree male relative who developed breast cancer; or
      5. The individual for whom the test is requested, has a first- or second-degree relative who had triple negative breast cancer diagnosed at age 60 or less; or
      6. The individual for whom the test is requested, has a first- or second-degree relative with breast cancer and that relative has a first-, second- or third-degree male relative with breast cancer; or
      7. The individual for whom the test is requested, has a first- or second-degree relative with a history of breast cancer and 2 or more first-, second-, or third-degree relatives on the same side of the family with pancreatic cancer; or
      8. The individual for whom the test is requested, has a first- or second-degree relative who has a history of ovarian, fallopian tube, or primary peritoneal cancer; or
      9. The individual for whom the test is requested, has a first- or second-degree relative with a history of pancreatic cancer and a first-, second-, or third-degree relative with breast cancer (diagnosed at or prior to 50 years of age) and/or ovarian, fallopian tube, primary peritoneal or pancreatic cancer at any age; or
      10. The individual for whom the test is requested, has a first- or second-degree relative with history of breast cancer, and that relative has at least 2 or more first-, second- or third-degree relatives on the same side of the family with breast cancer; or
      11. The individual for whom the test is requested, has a first- or second-degree relative with breast cancer, and that relative has at least 1 first-, second-, or third-degree relative with ovarian, fallopian tube or primary peritoneal cancer; or
      12. The individual for whom the test is requested, has a first- or second-degree relative who has a history of breast cancer and that relative belongs to a population at risk for specific mutations due to ethnic or racial background (African American, Ashkenazi Jewish, Icelandic, Swedish, Hungarian or Dutch descent); or
      13. The individual for whom the test is requested, has a first- or second-degree relative of Ashkenazi Jewish descent with a history of pancreatic cancer; or
    4. For individuals with a family history of three or more first-, second- or third-degree relatives with ovarian, fallopian tube or primary peritoneal cancer or breast cancer, (at least one of which has breast cancer at or before age 50); and
    5. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.
  2. Large genomic rearrangement testing (BART) to identify individuals at risk for BRCA1/2 related cancers is considered medically necessary for individuals who meet any of the criteria above for BRCA1/2 genetic sequence testing, but have negative results from that testing.

Investigational and Not Medically Necessary:

  1. Genetic testing for cancer susceptibility is considered investigational and not medically necessary in individuals not meeting any of the criteria above.
  2. Genetic testing for cancer susceptibility using the BRACAnalysis® Rearrangement Test [BART] is considered investigational and not medically necessary in individuals not meeting criteria above.
  3. Genetic testing for breast and/or ovarian cancer susceptibility using panels of genes (with or without next-generation sequencing), including, but not limited to BreastNext™, BREVAGen, or OvaNext™, are considered investigational and not medically necessary unless all components of the panel have been determined to be medically necessary based on the criteria above. However, individual components of a panel may be considered medically necessary when criteria above are met.

Note: When a component of a genetic panel is separately identified, but a specific medical necessity statement is not found above or in another document, the criteria in GENE.00001 Genetic Testing for Cancer Susceptibility may be used to determine medical necessity.

Rationale

BRCA1 and BRCA2
The use of genetic testing for point mutations in the BRCA1 and BRCA2 genes may influence individual management in a variety of ways.  Individuals with point gene mutation may consider increased surveillance for breast cancer, or consider a prophylactic mastectomy or oophorectomy.  Family members of an individual with a known point mutation, who test negative for a mutation, can forego increased surveillance and/or consideration of prophylactic surgery.  Genetic testing for point mutations BRCA1 and BRCA2 genes has emerged as a widely accepted test, when accompanied by genetic counseling. 

Studies indicate that a woman with mutations in either BRCA1 or BRCA2 carries a lifetime breast cancer risk of 41-90%, and an 8-62% cumulative lifetime risk of ovarian cancer, depending on the population studied.  It is unclear whether the disease expression in mutation carriers is related to the specific mutation identified in a family or whether additional factors, either genetic or environmental, affect the disease expression.  BRCA1 mutations may also increase a woman's risk of developing peritoneal and fallopian tube cancer.  Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are also at increased risk of developing breast and/or prostate cancer (NCCN, 2016; NCI, 2015). 

Men and women with BRCA1 or BRCA2 mutations may be at increased risk of developing pancreatic cancer.  Murphy and colleagues (2002) investigated the role of germ-line mutations in the etiology of pancreatic cancer.  Researchers analyzed samples isolated from individuals with pancreatic cancer who were from well-defined pancreatic cancer kindreds (three or more members were affected with pancreatic cancer, at least two of which were first-degree relatives).  BRCA2 mutations were identified in 17% of the samples.  In another study which explored BRCA1 and BRCA2 germline mutations in individuals of Ashkenazi descent with pancreatic cancer, BRCA1 and BRCA2 mutations were identified in 1.3% and 4.1% respectively (Ferrone, 2009; Murphy, 2002). 

The prevalence of BRCA1 and BRCA2 mutations is not the same amongst all racial and ethnic populations.  Several ethnic and geographic populations, such as the Norwegian, Dutch, Icelandic peoples and those of Ashkenazi descent have a higher prevalence of specific harmful BRCA1 and BRCA2 mutations.  Researchers have also investigated the frequency of BRCA1 and BRCA mutations in non-hispanic white and black women.  John and colleagues (2007) reported a BRCA1 mutation frequency of 16.7% amongst black women from California who were diagnosed with breast cancer prior to 35 years of age.  Pal and colleagues (2015) analyzed the BRCA mutation frequency and family history of 396 black women residing in Florida who were diagnosed with invasive breast cancer prior to the age of 50.  The researchers determined that 12.4 % of the study participants had either BRCA1 or BRCA2 mutations and for participants 35 years of age or younger, 19.4% had BRCA1 mutations while 4.2% had BRCA2 mutations.  Additionally, more than 40% of the individuals with a mutation had no close relatives with breast or ovarian cancer, which suggests that family history alone may not be sufficient to identify those at risk for carrying a BRCA mutation.  The researchers noted that amongst the BRCA1 carriers, the rate of prevalence decreased as the age of onset increased whereas amongst the BRCA2 carriers, the overall prevalence of mutations was 4.3% and this finding was similar for women in all age categories.  The authors concluded that based on the results of this study, "It is appropriate to recommend BRCA testing in all black women with invasive breast cancer who are diagnosed at age ≤ 50 years, regardless of family history."

The goal of BRCA1 and BRCA2 testing is to provide individuals and their physicians with information that will allow them to make informed decisions regarding cancer prevention, screening, surveillance, and treatment options (e.g., prophylactic surgery).  A significant benefit of genetic testing is the ability to quantify cancer risk estimates more precisely, thereby improving the process of determining the most appropriate management strategies in individuals who test positive.  For individuals who test negative, unnecessary treatment (e.g., prophylactic surgery) may be avoided.

There are some histopathologic features that have been noted to occur more frequently in breast cancers that are associated with BRCA1 or BRCA2 mutation.  Several studies have demonstrated that BRAC1 breast cancer is more likely to be characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative, also referred to as triple negative breast cancer.  Studies have indicated BRCA1 mutations in 9% to 28% of individuals with triple-negative breast cancer.  It has also been noted that in those with triple-negative disease, the BRCA mutation carriers were diagnosed at a younger age compared to non-carriers (NCCN, 2017).

There is evidence in the published, peer-reviewed scientific literature to demonstrate that testing methods used to identify BRCA mutations are accurate in detecting specific mutations.  If a BRCA1 or BRCA2 mutation is identified within a family, unaffected family members can also be tested for the presence of a mutation, and those testing negative can be provided with the reassurance that their risk of developing breast or ovarian cancer is more similar to that of the general population.  Sensitivity of BRCA testing has been reported to be up to 98% of all mutations, and sequencing should detect almost 100% of all nucleotide differences.  The specificity of BRCA testing has not been well studied.

Evidence in the published, peer-reviewed scientific literature indicates that BRCA1 and BRCA2 genetic testing is appropriate for a specific subset of adult individuals who have been identified to be at high risk for hereditary breast and ovarian cancers.  Furthermore, several specialty organizations, including the NCCN, American College of Medical Genetics (ACMG), and American Society of Clinical Oncology (ASCO), have issued statements recognizing the role of BRCA testing in the management of at-risk individuals.  The U.S. Preventive Services Task Force (USPSTF) has published recommendations regarding genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility.  Studies have demonstrated that individuals with BRCA mutations are at increased risk for developing breast and ovarian cancer (Moyer, 2014).

Large rearrangements of DNA in the BRCA1 and BRCA2 genes (BRACAnalysis® Rearrangement Test [BART])
The BRACAnalysis® Rearrangement Test (BART) is a refinement of the BRCA genetic tests and is purported to detect rare, large rearrangements of deoxyribonucleic acid (DNA) in the BRCA1 and BRCA2 genes which were previously undetected by standard genetic testing.  The manufacturer (Myriad Genetic Laboratories) reports that BART testing will identify an additional approximate 3% of BRCA1 and BRCA2 mutations in very high-risk families and is intended for use only in women at an exceptionally high risk for breast cancer who have previously tested negative for BRCA1 and BRCA2 sequence mutations. 

Walsh and colleagues (2006) reported on probands from 300 families in the United States with 4 or more cases of breast or ovarian cancer but who had tested negative (wild-type) with commercial genetic tests for BRCA1 and BRCA2 mutations.  These individuals were screened using additional multiple DNA -based and RNA-based methods to detect genetic mutations including genomic rearrangements in BRCA1 and BRCA2.  Of the 300 individuals participating in the study, 35 (12%) carried previously undetected genomic rearrangements of BRCA1 or BRCA2.  Palma and colleagues (2008) evaluated 251 individuals with an estimated risk of BRCA mutation of greater than or equal to 10% using the Myriad II model.  In the 136 non-Ashkenazi Jewish probands, 36 (26%) had BRCA point mutations and 8 (6%) had genomic rearrangements, (with 7 in BRCA1 and 1 in BRCA2).  Point mutations were identified in 47 of the 115 (40%) Jewish probands.  There were no genomic rearrangements identified in the group without mutations.  In the non-Ashkenazi Jewish probands, large genomic rearrangements accounted for 18% of all identified BRCA mutations.  The estimated prevalence of a mutation using the Myriad II model was not predictive of the presence of a genomic rearrangement. 

Since large genomic rearrangements, such as translocations, inversions, deletions or insertions, are missed by most techniques including standard DNA sequencing, supplemental testing (e.g., BART) has been recommended (NCCN, 2015) for select high-risk individuals.  These large genomic rearrangements are estimated to be responsible for 12% to 18% of BRCA1 inactivating mutations, although less is often seen in BRCA2 and, as noted above, in individuals of Ashkenazi Jewish descent (Shannon, 2011).

Genetic Testing Using Panels of Genes
Until recently, genetic testing for cancer susceptibility was generally carried out by direct sequencing which analyzes a specific gene for a particular mutation.  However, next-generation sequencing, (including but not limited to massively parallel sequencing, and microarray testing) has made it possible to conduct panel testing which involves the analysis of multiple genes for multiple mutations simultaneously.  Panel testing has the potential benefit of analyzing multiple genes more rapidly and thereby providing the results of the genetic work-up in a more timely fashion.  However, the newer sequencing techniques may be associated with a higher error rate and lower diagnostic accuracy than direct sequencing which could affect the clinical validity of testing.  Another potential drawback of the newer technologies is that they may provide information on genetic mutations which is of uncertain clinical significance.  In assessing the value of a specific genetic testing panel for susceptibility to a particular malignant condition, consideration should be given to the peer-reviewed, published literature addressing the analytical validity, clinical validity, and clinical utility of the test.  Also, evidence demonstrating a positive impact of the panel on the care of individuals with, or at risk for, a specific cancer should be considered.

In 2015, ASCO issued a policy statement update regarding genetic and genomic testing for cancer susceptibility.  The findings and conclusions regarding the current state of the technology are summarized as follows:

There is limited published evidence for the clinical utility and clinical validity of specific genetic test panels for breast and/or ovarian cancer susceptibility.  While testing these genes may be appropriate in individuals with clinical or family histories suggestive of a specific syndrome, there is no evidence that mass screening of multiple genes in individuals suspected of having or being at risk for breast and/or ovarian cancer syndrome improves clinical outcomes.  The specific genes included in these test panels and the particular next-generation sequencing technology utilized may differ between manufacturers.  At the present time, there is limited published information on their analytical validity, clinical utility or clinical validity.

Background/Overview

BRCA1 and BRCA2
Between 5% and 10% of women with breast cancer develop the disease due to the inheritance of a mutated copy of BRCA1 or BRCA2 genes.  Families suspected of having hereditary breast and/or ovarian cancer are characterized by cancer occurring in premenopause, in multiple generations, often bilaterally and in a pattern suggesting an autosomal dominant pattern of inheritance.  A positive test result indicates that a person has inherited a known BRCA1 or BRCA2 gene mutation, and has an increased risk of breast and/or ovarian cancer.  Mutations of BRCA1 and BRCA2 are present in 1-2% of individuals of Ashkenazi Jewish ancestry.

At the present time genetic testing for BRCA mutations is not applied universally but rather to individuals that exhibit personal or family histories that suggest an inherited predisposition to (and hence, have a high likelihood of finding) one of these mutations.  The NCCN guidelines (2017) include the following information with regard to the selection of appropriate candidates to undergo genetic testing:

The genetic testing strategy is greatly facilitated when a deleterious mutation has already been identified in another family member.  In that case, the genetic testing laboratory can limit the search for mutations in additional family members to the same location in the gene … For the majority of families in who mutation status is unknown, it is best to consider testing an affected family member first, especially a family member with early-onset disease, bilateral disease, or multiple primaries, because that individual has the highest likelihood for a positive test result …

In the situation of an unaffected individual with a significant family history, the testing of the unaffected individual (or of unaffected family members) should only be considered when no affected family member is available for testing.  In such cases, the unaffected individual or unaffected close relative with the highest likelihood of testing positive for the mutation should be tested.  A negative test result in such cases, however, is considered indeterminate … and does not provide the same level of information as when there is a known deleterious mutation in the family…

In unaffected individuals with a family history only (i.e., no personal history of breast or ovarian cancer), significant limitations of interpreting test results should be discussed prior to any testing. Moreover, testing of unaffected individuals should only be considered when an appropriate affected family member is unavailable for testing.  Clinical judgment should be used to evaluate each unaffected individual for his/her likelihood of carrying the mutation based on factors such as the unaffected individual's current age and the age of the unaffected female relative who link the individual with an affected close relative (NCCN, 2017).

The NCCN guidelines also point out that the chances of mutation detection may be very low in families with a large number of unaffected female relatives.  Genetic counseling is an integral part of the testing process and provides the candidate with opportunity to be made aware of the potential benefits, limitations, and risks of genetic testing (NCCN, 2017).

Large rearrangements of DNA in the BRCA1 and BRCA2 genes (BRACAnalysis® Rearrangement Test [BART])
As mentioned above, the BRACAnalysis® Rearrangement Test (BART) is a refinement of the BRCA genetic tests and is used to detect rare, large rearrangements of deoxyribonucleic acid (DNA) in the BRCA1 and BRCA2 genes which were previously undetected by standard genetic testing.  BART testing can be used to identify additional BRCA1 and BRCA2 mutations in women at high risk for breast cancer who have previously tested negative for BRCA1 and BRCA2 sequence mutations.

Genetic Testing Using Panels of Genes
Next-generation sequencing addresses any of the technologies that allow rapid sequencing of large numbers of segments of DNA, up to and including entire genomes.  Next-generation sequencing is not a specific sequencing technology or a test in itself.  Instead, the term emphasizes the difference between the earlier testing methods that involved the sequencing of one DNA strand at a time.  Next-generation sequencing includes but is not limited to massively parallel sequencing and microarray analysis. 

Next-generation sequencing has led to the development of genetic testing incorporating panels which analyze multiple genes for multiple mutations simultaneously.  Researchers are investigating genetic testing using panels of genes as a means to identify genetic mutations that may contribute to the development of hereditary cancers.  Commercially available genetic testing panels include, but are not limited to: BreastNext (Ambry Genetics™); OvaNext (Ambry Genetics™); BREVAGen (Phenogen Sciences); and myRisk Hereditary Cancer test (Myriad Genetics).

There is limited information in the peer-reviewed, published literature addressing the analytical validity, clinical validity, and clinical utility of these tests.  There were also no studies identified which demonstrated improved clinical outcomes for individuals at risk for breast and/or ovarian cancer syndrome as a result of using the genetic testing panels.    

Genetic Counseling
According to the National Society of Genetic Counselors (NSGC), genetic counseling is the process of assisting individuals to understand and adapt to the medical, psychological and familial ramifications of a genetic disease.  This process typically includes the guidance of a specially trained professional who:

  1. Integrates the interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
  2. Provides education about inheritance, genetic testing, disease management, prevention and resources; and
  3. Provides counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
  4. Provides counseling for the psychological aspects of genetic testing (NSGC, 2006).
Definitions

Ashkenazi Jewish: A term for people of eastern European Jewish heritage.

First-degree relative: Any relative who is a parent, sibling, or offspring to another.

Genetic testing: A type of test that is used to determine the presence or absence of a specific gene or set of genes to help diagnose a disease, screen for specific health conditions, and for other purposes.

Mutation: A change in DNA sequence.

Next-generation sequencing: Any of the technologies that allow rapid sequencing of large numbers of segments of DNA, up to and including entire genomes. This technology includes but is not limited to massively parallel sequencing and microarray analysis.

Penetrance: The likelihood that a clinical condition will occur when a particular genotype exists.

Second-degree relative: Any relative who is a grandparent, grandchild, uncle, aunt, niece, nephew, or half-sibling to another.

Third-degree relative: Any relative who is a first cousin, great grandparent or great grandchild.

Triple negative breast cancer: Breast cancer cells which lack estrogen receptors, progesterone receptors and large amounts of HER2/neu protein.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

81162

BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and full duplication/deletion analysis

81211

BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)

81212

BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; 185delAG, 5385insC, 6174delT variants

81213

BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; uncommon duplication/deletion variants [BART]

81214

BRCA1 (breast cancer 1) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants (ie, exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 8121404 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)

81215

BRCA1 (breast cancer 1) (eg, hereditary breast and ovarian cancer) gene analysis; known familial variant

81216

BRCA2 (breast cancer 2) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis

81217

BRCA2 (breast cancer 2) (eg, hereditary breast and ovarian cancer) gene analysis; known familial variant

 

 

ICD-10 Diagnosis

 

 

C50.011-C50.929

Malignant neoplasm of breast

 

C56.1-C56.9

Malignant neoplasm of ovary

 

Z13.71-Z13.79

Encounter for screening for genetic and chromosomal anomalies

 

Z15.01

Genetic susceptibility to malignant neoplasm of breast

 

Z15.02

Genetic susceptibility to malignant neoplasm of ovary

 

Z80.0

Family history of malignant neoplasm of digestive organs [pancreas]

 

Z80.3

Family history of malignant neoplasm of breast

 

Z80.41

Family history of malignant neoplasm of ovary

 

Z80.49

Family history of malignant neoplasm of other genital organs [fallopian tube]

 

Z80.8

Family history of malignant neoplasm of other organs or systems [peritoneum]

 

Z85.07

Personal history of malignant neoplasm of pancreas

 

Z85.3

Personal history of malignant neoplasm of breast

 

Z85.43

Personal history of malignant neoplasm of ovary

 

Z85.44

Personal history of malignant neoplasm of other female genital organs [fallopian tube]

 

Z85.89

Personal history of malignant neoplasm of other organs and systems [peritoneum]

 

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Panels
When services are Investigational and Not Medically Necessary:

CPT

 

81432

Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); genomic sequence analysis panel, must include sequencing of at least 10 genes, always including BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, and TP53

81433

Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11

 

 

ICD-10 Diagnosis

 

 

All diagnoses

When services are also Investigational and Not Medically Necessary:

CPT

 

81445

Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed

81455

Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm, DNA analysis, and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MLL, NPM1, NRAS, MET, NOTCH1, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed

 

 

ICD-10 Diagnosis

 

C50.011-C50.929

Malignant neoplasm of breast

C56.1-C56.9

Malignant neoplasm of ovary

Z15.01

Genetic susceptibility to malignant neoplasm of breast

Z15.02

Genetic susceptibility to malignant neoplasm of ovary

Z80.0

Family history of malignant neoplasm of digestive organs [pancreas]

Z80.3

Family history of malignant neoplasm of breast

Z80.41

Family history of malignant neoplasm of ovary

Z80.49

Family history of malignant neoplasm of other genital organs [fallopian tube]

Z80.8

Family history of malignant neoplasm of other organs or systems [peritoneum]

Z85.07

Personal history of malignant neoplasm of pancreas

Z85.3

Personal history of malignant neoplasm of breast

Z85.43

Personal history of malignant neoplasm of ovary

Z85.44

Personal history of malignant neoplasm of other female genital organs [fallopian tube]

Z85.89

Personal history of malignant neoplasm of other organs and systems [peritoneum]

References

Peer Reviewed Publications:

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  15. Murphy KM, Brune KA, Griffin C, et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res. 2002; 62(13):3789-3793.
  16. Pal T, Bonner D, Cragun D, et al. A high frequency of BRCA mutations in young black women with breast cancer residing in Florida. Cancer. 2015; 121(23):4173-4180.
  17. Palma MD, Domchjeck SM, Stopfer J, et al. The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families Cancer Res. 2008; 68(17):7006-7014.
  18. Shannon KM, Rodgers LH, Chan-Smutko G, et al. Which individuals undergoing BRACAnalysis need BART testing? Cancer Genet. 2011; 204(8):416-422.
  19. Smith LD, Tesoriero AA, Wong EM, et al. Contribution of large genomic BRCA1 alterations to early-onset breast cancer selected for family history and tumor morphology: a report from The Breast Cancer Family Registry. Breast Cancer Res. 2011; 13(1):R14.
  20. Smith RA, Cokkinides V, Brawley OW.  Cancer screening in the United States, 2009: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin. 2009; 59(1):27-41.
  21. Susswein LR, Marshall ML, Nusbaum R, et al. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med. 2016; 18(8):823-832.
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Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Board of Genetic Counselors. Genetic Counselors' Scope of Practice. Available at: http://www.abgc.net/docs/GC_Scope_of_prractice_final.pdf. Accessed on April 9, 2017.
  2. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 103: Hereditary breast and ovarian cancer syndrome. Obstetrics & Gynecology 2009; 113(4):957-966. Reaffirmed 2010.
  3. American Society of Breast Surgeons: Consensus Guideline on Hereditary Genetic Testing for Patients With and Without Breast Cancer. Updated September 13, 2016. Available at: https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/BRCA_Testing.pdf . Accessed on October 24, 2016.
  4. Lancaster JM1, Powell CB2, Chen LM, et al. Society of Gynecologic Oncology (SGO) Clinical Practice Committee. SGO statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2015; 136(1):3-7.
  5. Moyer VA; U.S. Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014; 160(4):271-281.
  6. National Cancer Institute (NCI). Genetics of Breast and Ovarian Cancer (PDQ) 2012. Last modified October 7, 2016. Available at: http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page1. Accessed on October 24, 2016.
  7. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. © 2016 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on October 23, 2016.
    • Breast Cancer (V2.2016). Revised May 6, 2016.
    • Genetic/familial high-risk assessment: breast and ovarian. (V1.2017). Revised September 19, 2016.
  8. National Society of Genetic Counselors' Definition Task Force, Resta R, Biesecker BB, et al. A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report. J Genet Couns. 2006; 5(2):77-83.
  9. Nelson HD, Fu R, Goddard K, et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Evidence Syntheses, No. 101. 2013. Available at: http://www.ncbi.nlm.nih.gov/books/NBK179201/. Accessed on October 24, 2016.
  10. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology Policy statement update:  genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015; 33:3660-3667. Available at: http://jco.ascopubs.org/content/early/2015/08/31/JCO.2015.63.0996.full. Accessed on October 23, 2016.
Websites for Additional Information
  1. National Library of Medicine (NLM). Genetics Home Reference. Available at: http://ghr.nlm.nih.gov/. Accessed on October 23, 2016.
Index

BART (BRCA1/2 Rearrangement Test)
BRCA1
BRCA2
BRCAdvantage™
BRCAssureSM 
BreastNext Test
BREVAGen
Genetic testing panels
Genetic testing using panels
myRisk Hereditary Cancer test
OvaNext Test

Document History
Status Date Action
  12/27/2017 The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 CPT descriptor change for code 81432.
Revised 05/04/2017 Medical Policy & Technology Assessment Committee (MPTAC) review.
Revised 05/03/2017 Hematology/Oncology Subcommittee review. Updated the medically necessary statements to include criteria for genetic counseling. Updated the formatting of the Position Statement section. The Background/Overview, Definitions and References sections were updated.
Reviewed 11/03/2016 MPTAC review.
Reviewed 11/02/2016 Hematology/Oncology Subcommittee review. Updated the formatting of the Position Statement section. The Rationale, Background/Overview and References were updated.
  01/01/2016 Updated Coding section with 01/01/2016 CPT changes.
Revised 11/05/2015 MPTAC review.
Revised 11/04/2015 Hematology/Oncology Subcommittee review. Revisions to medically necessary criteria include but are not limited to the following: (1) Clarified the meaning of multiple primary breast cancers; (2) Expanded criteria to include individual with a history of pancreatic cancer and 2 or more first-, second-, or third-degree relatives on the same side of the family with breast (diagnosed at or prior to 50 years of age), ovarian, fallopian tube, primary peritoneal or pancreatic cancer. Updated review date, Rationale, Background/Overview, References, Index and History sections. Removed ICD-9 codes from Coding section.
Revised 11/13/2014 MPTAC review.
Revised 11/12/2014 Hematology/Oncology Subcommittee review. Expanded medically necessary criteria to include genetic testing for a BRCA1 or BRCA2 mutation for an individual who is or has a family member of Ashkenazi Jewish descent with a history of pancreatic cancer and a first-, second-, or third-degree relative on the same side of the family with breast, ovarian, fallopian tube, primary peritoneal or pancreatic cancer. Updated review date, Rationale, References and History sections. Updated Coding section to include 01/01/2015 CPT changes.
New 11/14/2013 MPTAC review.
New 11/13/2013 Hematology/Oncology Subcommittee review. Initial document development. Clinical content relevant to breast and ovarian cancer moved from GENE.00001 to this document.