Medical Policy

 

Subject: Genetic Testing for Breast and/or Ovarian Cancer Syndrome
Document #: GENE.00029 Publish Date:    08/29/2018
Status: Revised Last Review Date:    07/26/2018

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 BRCA (BRCA1 and/or BRCA2) mutations and/or large genomic rearrangements (BART) 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 E and all of the criteria in F 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 14 are met:
      1. The individual was diagnosed with breast cancer at age 45 years or less; 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); and
        1. Testing for a specific founder mutation(s) is negative; or
        2. The individual’s ancestry includes more than one ethnicity; or
        3. The individual meets other BRCA1 or BRCA2 testing criteria; or
      14. The individual has a history of relapsed/refractory human epidermal growth factor receptor 2 (HER2) negative, metastatic breast cancer previously treated with chemotherapy and is a candidate for poly (ADP-ribose) polymerase (PARP) inhibitor therapy; 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 at age 45 years or less; 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 of Ashkenazi Jewish descent with a history of pancreatic cancer; or
      11. 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
      12. 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
      13. 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); and
        1. Testing for a specific founder mutation(s) is negative; or
        2. The individual’s ancestry includes more than one ethnicity; or
        3. The individual meets other BRCA1 or BRCA2 testing criteria; 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); or
    5. For individuals who require confirmatory testing for a BRCA1/BRCA2 mutation(s) detected by a Food and Drug Administration (FDA)-authorized direct-to-consumer (DTC) test report; and
    6. 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.

Investigational and Not Medically Necessary:

  1. Genetic testing for breast and/or ovarian cancer susceptibility (BRCA1, BRCA2 and/or large genomic rearrangements) is considered investigational and not medically necessary in individuals not meeting any of the criteria above.
  2. 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 Gene Mutations and Cancer Susceptibility
BRCA1 is located on chromosome 17 and BRCA2 is positioned on chromosome 13.  Both BRCA genes are tumor suppressor genes that encode proteins that play a role in the DNA repair process (ACOG, 2017).

Germline mutations in the BRCA1 and BRCA2 (BRCA) genes account for the majority of cases of hereditary breast and ovarian cancer syndrome.  It has been estimated that approximately 4.5% of cases of breast cancer and 9–24% of cases of epithelial ovarian cancer are due to germline BRCA1 and BRCA2 mutations.  According to the American College of Obstetricians and Gynecologists (ACOG), for a woman harboring the BRCA1 mutation, the risk of ovarian cancer (including primary peritoneal cancer and fallopian tube cancer) by age 70 years is approximately 39-46%.  For a woman carrying a BRCA2 mutation, the risk of ovarian cancer is 10-27% by age 70 years.  Ovarian cancer associated with BRCA1 and BRCA2 mutations is usually high grade and has a distinct histologic phenotype that is predominantly endometrioid or serous.  A woman with high-grade ovarian cancer has a 9-24% probability of carrying a BRCA1 or BRCA2 germline mutation.  Mutations in the BRCA genes have also been associated with other types of cancer.  Individuals with BRCA mutations are also at increased risk (albeit smaller than their risk of breast and ovarian cancer) for prostate cancer, pancreatic cancer, melanoma, and potentially uterine cancer (ACOG, 2017).

In the general population, it has been estimated that approximately 1 in 300 to 1 in 800 individuals carry a BRCA1 or BRCA2 mutation.  However, the prevalence of BRCA1 and BRCA2 mutations is not the same amongst all racial and ethnic populations.  In certain populations founded by a small ancestral group, a specific BRCA1 or BRCA2 mutation may occur more often, and is often referred to as a founder mutation.  Several ethnic and geographic populations, including but not limited to the Ashkenazi (Central and Eastern European) Jews, French Canadians, and Icelanders have a higher prevalence of specific harmful BRCA1 and BRCA2 mutations.  BRCA mutations also have been found in individuals of diverse ethnic backgrounds, including Hispanic, Asian and African American (ACOG, 2017; Hall, 2009; Nanda, 2005).  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 BRCA1 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.  For example, a female with triple negative breast cancer has a 10-39% probability of having a BRCA1 or BRCA2 mutation, with BRCA1 being more probable.  In contrast, women with BRCA2 mutations are more likely to be estrogen-receptor and progesterone-receptor positive (ACOG, 2017).  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.

BRCA1 and BRCA2 testing is currently available individually or as part of multiplex gene panels from a variety of commercial laboratories.  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 and the testing will impact the medical management of the tested individual or their at-risk family members.  Furthermore, several specialty organizations, including the National Comprehensive Cancer Networks (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).

The NCCN guidelines on Genetic/Familial High-Risk Assessment: Breast and Ovarian Guidelines recommend that mutation testing begin with a relative (male or female) with known BRCA-related cancer to ascertain if a clinically significant mutation is present in the family prior to testing individuals without cancer.  If an affected family member is not available for testing, then testing should be conducted on the relative with the highest probability of a BRCA mutation.  Ideally, the results of the initial test will be used to guide testing decisions of other family members.  Individuals without a personal history of cancer but who may fulfill the NCCN criteria for testing include those from families with known deleterious BRCA1 or BRCA2 mutations or from families with extensive cancer history (NCCN, 2018)

The type of gene mutation analysis required is dependent upon family history.  Historically, BRCA mutation testing was comprised of single-site testing.  However, due to technological advances, option for BRCA mutation testing may now consist of targeted multisite mutation testing, comprehensive gene sequencing, and BRCA rearrangement testing.  It may be appropriate for individuals from families with known mutations, or from ethnic groups with common mutations, to be tested for those specific mutations.  Individuals without linkages to families or groups with known mutations may undergo direct DNA sequencing (Nelson, 2013).

The NCCN recommends that:

For the majority of families in whom 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. Unless the affected individual is a member of an ethnic group for which particular founder gene mutations are known, comprehensive genetic testing (ie, full sequencing of the genes and detection of large gene rearrangements) should be performed.

For individuals with family histories consistent with a pattern of hereditary breast and/or ovarian cancer on both the maternal and paternal sides, the possibility of a second deleterious mutation in the family should be considered, and full sequencing may be indicated, even if a mutation has already been identified in a relative (NCCN, 2018).

ACOG states the following regarding BRCA testing:

If a specific BRCA mutation is identified in an affected individual, a single-site test can be recommended for family members to look for that specific genetic mutation already identified (ie, “predictive testing”).  For members of certain ethnic and geographic groups who are at risk of founder mutations, but who do not have a personal or family history of breast or ovarian cancer, targeted multisite testing for common mutations can be performed and is less expensive than full sequence testing. Genetic testing has evolved over the years so patients who underwent BRCA genetic testing before the routine initiation of BRCA Rearrangement Testing, may need repeat testing or evaluation (ACOG, 2017).

BRCA Mutation Status and Treatment for Metastatic Breast Cancer
In January 2018, the United States Food and Drug Administration (FDA) approved olaparib (Lynparza®, AstraZeneca, Wilmington, DE), for use in individuals with deleterious or suspected deleterious germline BRCA-mutated HER2-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting.  In addition to other criteria, the product information indicates that individuals should be selected for therapy based on the FDA-approved companion diagnostic test (BRACAnalysis CDx) from Myriad Genetics.  The FDA approval was based on data from the randomized, open-label, Phase III OlympiAD trial (Robson, 2017), which examined olaparib versus physician’s choice of chemotherapy (capecitabine, eribulin or vinorelbine). 

Large rearrangements of DNA in the BRCA1 and BRCA2 genes
Prior to the development of next generation sequencing (also known as massively parallel sequencing), genetic testing was generally carried out using traditional (Sanger) DNA sequencing.  Because the traditional DNA sequencing method does not identify large gene rearrangements such as deletions or duplications, a separate technology/test was necessary to detect large genomic rearrangements (Hogervorst 2003).  Next generation sequencing accurately detects large genomic alterations such as translocations, inversions, or large deletions or insertions that are overlooked by most genetic testing techniques, including direct DNA sequencing.  Such rearrangements are believed to be responsible for approximately 12% to 18% of BRCA1 inactivating variants but are less frequently observed in BRCA2 and in individuals of Ashkenazi Jewish descent.  Additionally, studies have indicated that these rearrangements may occur more frequently in Caribbean and Hispanic populations (NCI, 2017; Walsh, 2010).

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.

Because certain large genomic rearrangements, such as translocations, inversions, deletions or insertions, are not detectable by standard DNA sequencing, supplemental testing of large genomic rearrangements (e.g., BART™) has been recommended (NCCN, 2018) 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.  The NCCN emphasizes the need for comprehensive testing, which includes full BRCA1 and BRCA 2 sequencing as well as the detection of large gene rearrangements (NCCN, 2018; 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.

Confirmatory Testing for a BRCA1/BRCA2 mutation(s) Detected by a Food and Drug Administration (FDA)-Authorized Direct-to-Consumer (DTC) Test Report
In March 2018, the FDA granted the genetic testing company 23andMe® approval to provide direct-to-consumer genetic testing and to report on selected conditions, including but not limited to three genetic variants of the breast cancer susceptibility genes (BRCA1/BRCA2).  The three BRCA variations (founder mutations) represent the most common breast cancer risk genes in individuals of Eastern European (Ashkenazi) Jewish decent (present in approximately 2% of Ashkenazi Jewish women but rarely [0 percent to 0.1 percent] in other ethnic populations).  Women with one of these three variants, which account for approximately 90% of BRCA mutations identified in Ashkenazi Jewish women, have a 45-85% probability of developing breast cancer by age 70. 

The FDA approval obtained by 23andMe was based on the agency’s review of data which determined that the company provided sufficient data to demonstrate that the test is accurate (i.e., can correctly identify the three genetic variants in saliva samples), and can provide reproducible results.  Of equal importance, the FDA determined that 23andMe will provide consumers with appropriate instructions and a test report which describes what the BRCA test results mean, how the results should be interpreted and where additional information can be accessed.  The FDA notes that consumers and health care professionals should not use test results obtained from the 23andMe report to determine treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries, and that such decisions require confirmatory testing and genetic counseling. 

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 (2018) 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.  Unless the affected individual is a member of an ethnic group for which particular founder gene mutations are known, comprehensive genetic testing (ie, full sequencing of the genes and detection of large gene rearrangements) should be performed…

For individuals with family histories consistent with a pattern of hereditary breast and/or ovarian cancer on both the maternal and paternal sides, the possibility of a second deleterious mutation in the family should be considered, and full sequencing may be indicated, even if a mutation has already been identified in a relative.

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 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 individuals without a cancer diagnosis should only be considered when an appropriate affected family member is unavailable for testing.  When evaluating an individual without a cancer diagnosis for his or her likelihood of carrying a BRCA1/2 mutation, clinical judgment should be made based on factors such as the individual’s current age and the age of the unaffected female relative who link the individual with an affected close relative (NCCN, 2018).

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, 2018).

Large rearrangements of DNA in the BRCA1 and BRCA2 genes (BRACAnalysis® Rearrangement Test [BART])
In 20016, the BRACAnalysis® Rearrangement Test™ (BART) was introduced to the market as a refinement of the BRCA genetic tests and was used to detect rare, large rearrangements of deoxyribonucleic acid (DNA) in the BRCA1 and BRCA2 genes which were previously undetected by standard genetic testing.  Since then, Myriad has included BART testing as part of the Comprehensive BRACAnalysis test.

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.   

Confirmatory Testing for a BRCA1/BRCA2 mutation(s) Detected by a Food and Drug Administration (FDA)-Authorized DTC Test Report
In March 2018, 23andMe received FDA approval as the first DTC test to report on three specific BRCA1/BRCA2 breast cancer gene mutations that are most common in people of Ashkenazi (Eastern European) Jewish descent.  The 23andMe Genetic Health Risk Test examines DNA collected from a saliva sample to report if a woman is at increased risk of developing ovarian or breast cancer, and if a man is at increased risk of developing breast cancer or prostate cancer.  The test only identifies 3 out of more than 1000 known BRCA mutations.  Therefore, a negative result does not rule out the possibility that an individual carries other BRCA mutations that may put them at increased risk for cancer.  The FDA also cautioned that the test results should not be used to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries and that such decisions warrant confirmatory testing and genetic counseling.

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.

Founder mutation: A particular mutation occurring among defined ethnic groups or individuals from a specific geographic area that is traceable back to a common ancestor.

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.

Germline mutation: Any detectable and heritable change in the lineage of germ cells.  Mutations in these cells are transmitted to offspring, while, on the other hand, somatic mutations are not inherited.

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.

Poly (ADP-ribose) polymerase (PARP) inhibitors: Any one of a group of enzymes (including PARP1, PARP2 and PARP3) which play a role in DNA damage/repair pathways.  PARP inhibitors have also been explored as antitumor agents.

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

 

R85.89

Other abnormal findings in specimens from digestive organs and abdominal cavity

 

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:

  1. Armstrong J, Toscano M, Kotchko N, et al. American BRCA Outcomes and Utilization of Testing (ABOUT) Study: a pragmatic research model that incorporates personalized medicine/patient-centered outcomes in a real world setting. J Genet Couns. 2015; 24(1):18-28.
  2. Chong HK, Wang T, Lu HM, et al. The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay. PLoS One. 2014; 9(5):e97408.
  3. de la Hoya M, Gutiérrez-Enríquez S, Velasco E, et al. Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer. Clin Chem. 2006; 52(8):1480-1485.
  4. Ferrone CR, Levine DA, Tang LH, et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009; 27(3):433-438.
  5. Gad S, Scheuner MT, Pages-Berhouet S, et al. Identification of a large rearrangement of the BRCA1 gene using color bar code on combed DNA in an American breast/ovarian cancer family previously studied by direct sequencing. J Med Genet. 2001; 38(6):388-392.
  6. Gutiérrez-Enríquez S, de la Hoya M, Martínez-Bouzas C, et al. Screening for large rearrangements of the BRCA2 gene in Spanish families with breast/ovarian cancer. Breast Cancer Res Treat. 2007; 103(1):103-107.
  7. Hall MJ, Reid JE, Burbidge LA, et al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009; 115(10):2222-2233.
  8. Hogervorst FB, Nederlof PM, Gille JJ, et al. Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res. 2003; 63(7):1449-1453.
  9. John EM, Miron A, Gong G, at al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA. 2007; 298(24):2869-2876.
  10. Judkins T, Leclair B, Bowles K, et al. Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk. BMC Cancer. 2015; 15:215.
  11. Karami, F, Mehdipour, P. A Comprehensive Focus on Global Spectrum of BRCA1 and BRCA2 Mutations in Breast Cancer. Biomed Res Int. 2013; 2013:928562.
  12. LaDuca H, Stuenkel AJ, Dolinsky JS, et al. Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014; 16(11):830-837.
  13. Lincoln SE, Kobayashi Y, Anderson MJ, et al. A systematic comparison of traditional and multigene panel testing for hereditary breast and ovarian cancer genes in more than 1000 patients. J Mol Diagn. 2015; 17(5):533-544.
  14. Lucas AL, Frado LE, Hwang C, et al. BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts. Cancer. 2014; 120(13):1960-1967.
  15. Manchanda R, Loggenberg K, Sanderson S, et al. Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial. J Natl Cancer Inst. 2014; 30; 107(1):379.
  16. Minion LE, Dolinsky JS, Chase DM, et al. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2. Gynecol Oncol. 2015; 137(1):86-92.  
  17. Mitra AV, Bancroft EK, Barbachano Y, et al. Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int. 2011; 107(1):28-39.
  18. 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.
  19. Nanda R, Schumm LP, Cummings S, et al. Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. JAMA 2005; 294:1925-1933.
  20. 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.
  21. 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.
  22. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998. Updated December 2016. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Updated December 15, 2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1247. Accessed on January 18, 2018.
  23. Robson M;Im SA;Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017; 377(6):523-533.
  24. Shannon KM, Rodgers LH, Chan-Smutko G, et al. Which individuals undergoing BRACAnalysis need BART testing? Cancer Genet. 2011; 204(8):416-422.
  25. 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.
  26. 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.
  27. 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.
  28. Tung N, Battelli C, Allen B, et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015; 121(1):25-33.
  29. Walsh T, Casadei S, Coats KH et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006; 295(12):1379-1388.
  30. Walsh T, Lee MK, Casadei S, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A. 2010; 107(28):12629-12633.
  31. Walsh T, Casadei S, Lee MK, 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):18032-18037.
  32. Weinstein LB. Selected genetic disorders affecting Ashkenazi Jewish families. Fam Community Health. 2007; 30(1):50-62.
  33. Weitzel JN, Lagos VI, Cullinane CA, et al. Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA. 2007; 297(23):2587-2595.
  34. Weitzel JN, Lagos VI, Herzog JS, et al. Evidence for common ancestral origin of a recurring BRCA1 genomic rearrangement identified in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2007; 16(8):1615-1620.
  35. Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994; 265(5181):2088-2090.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 182: Hereditary breast and ovarian cancer syndrome. Obstetrics & Gynecology 2017; 130(3):e110-e126..
  2. American Society of Breast Surgeons: Consensus Guideline on Hereditary Genetic Testing for Patients with and Without Breast Cancer. Updated March 14, 2017. Available at: https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/BRCA_Testing.pdf. Accessed on June 29, 2018.
  3. 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.
  4. 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.
  5. National Cancer Institute (NCI). Genetics of Breast and Ovarian Cancer (PDQ) 2012. Updated June 14, 2018. Available at: http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page1. Accessed on June 29, 2018.
  6. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on June 29, 2018.
    • Breast Cancer (V1.2018). Revised March 20, 2018.
    • Genetic/familial high-risk assessment: breast and ovarian. (V1.2018). Revised October 03, 2017.
  7. National Society of Genetic Counselors. Genetic Counselors' Scope of Practice. Available at: https://www.nsgc.org/p/cm/ld/fid=18%23scope%20-%20scope#scope. Accessed on June 29, 2018.
  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 June 29, 2018.
  10. Randall LM, Pothuri B, Swisher EM, et al. Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper. Gynecol Oncol. 2017; 146(2):217-224.
  11. 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.
  12. U.S. Food and Drug Administration (FDA). Office of In Vitro Diagnostics and Radiological Health. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Available at: https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed on June 29, 2018.
  13. U.S. Food and Drug Administration (FDA). FDA News Release. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes. Last updated: March 7, 2018. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm599560.htm. Accessed on June 29, 2018.
Websites for Additional Information
  1.  National Library of Medicine (NLM). Genetics Home Reference. Available at: http://ghr.nlm.nih.gov/. Accessed on June 29, 2018.
Index

23andme Genetic Health Risk
BART (BRCA1/2 Rearrangement Test)
BRACAnalysis CDX 
BRCA1
BRCA2
BRCAvantage®
BRCAssure®
BreastNext Test
BREVAGen
Genetic testing panels
Genetic testing using panels
myRisk Hereditary Cancer test
OvaNext Test

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Revised

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

07/18/2018

Hematology/Oncology Subcommittee review. Added medically necessary for individuals who require confirmatory testing for a BRCA1/BRCA2 mutation(s) detected by a Food and Drug Administration (FDA)-authorized direct-to-consumer (DTC) test report. Updated Rationale, Definitions, Coding, References, History and Index sections.

Revised

01/25/2018

MPTAC review.

Revised

01/17/2018

Hematology/Oncology Subcommittee review. Revised the medically necessary criteria so that BRCA1/BRCA2 testing is no longer required prior to BART. Age limit in bullets I-A-1 and I-B-1 changed from “prior to age 50” to “age 45 years or less”. Included additional criteria for individuals belonging to a population at risk for specific mutations due to ethnic or racial background (African American, Ashkenazi Jewish, Icelandic, Swedish, Hungarian or Dutch descent). Added medically necessary criteria for candidates for PARP inhibitor therapy. Updated the Rationale, Background/Overview, Definitions, References and Websites for Additional Information sections of the document. 

 

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

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.