BlueCross and BlueShield of Montana Medical Policy/Codes
Genetic Testing for Hereditary Breast and/or Ovarian Cancer (HBOC)
Chapter: Genetic Testing
Current Effective Date: October 25, 2013
Original Effective Date: October 21, 2002
Publish Date: October 25, 2013
Revised Dates: July 9, 2008; March 1, 2010; March 16, 2011; March 27, 2012; September 24, 2013
Description

Several genetic syndromes with an autosomal dominant pattern of inheritance that feature breast cancer have been identified. Of these, hereditary breast and ovarian cancer (HBOC) and some cases of hereditary site-specific breast cancer have in common causative mutations in BRCA (breast cancer) genes. Families suspected of having HBOC syndrome are characterized by an increased susceptibility to breast cancer occurring at a young age, bilateral breast cancer, male breast cancer, and ovarian cancer at any age. Other cancers, such as prostate cancer, pancreatic cancer, gastrointestinal cancers, melanoma, laryngeal cancer, occur more frequently in HBOC families. Hereditary site-specific breast cancer families are characterized by early onset breast cancer with or without male cases, but without ovarian cancer. For this policy, both will be referred to collectively as HBOC.

Germline mutations in the BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2) genes are responsible for the cancer susceptibility in the majority of HBOC families, especially if ovarian cancer or male breast cancer are features. However, in site-specific breast cancer, BRCA mutations are responsible for only a proportion of affected families, and research to date has not yet identified other moderate or high-penetrance gene mutations that account for disease in these families. BRCA gene mutations are inherited in an autosomal dominant fashion through either the maternal or paternal lineage. It is possible to test for abnormalities in BRCA1 and BRCA2 genes to identify the specific mutation in cancer cases, and to identify family members with increased cancer risk. Family members without existing cancer who are found to have BRCA mutations can consider preventive interventions for reducing risk and mortality.

Early age at diagnosis refers generally to diagnosis before age 45 or 50; an exact cutoff for testing affected individuals without known family history but with cancer diagnosis at an early age has not been established, although guidelines of the American College of Medical Genetics suggest age 45 or younger (see Rationale). The decision to test an affected individual based on age at diagnosis in the absence of family history will depend on the risk estimate for the individual patient (e.g., from widely available risk assessment computer programs) and the patient tolerance for risk, and the desire to inform the risk of family members.

As the majority of test results will be negative and uninformative in unaffected family members of potential BRCA mutation families, it is strongly recommended that an affected family member be tested first whenever possible to adequately interpret the test. Should a BRCA mutation be found in an affected family member(s), the DNA from the unaffected family member can be tested specifically for the same mutation of the affected family member without having to sequence the entire gene. Interpreting the test results for an unaffected family member without knowing the genetic status of the family may be possible in the case of a positive result for an established disease-associated mutation, but leads to difficulties in interpreting negative test results or mutations of uncertain significance because the possibility of a causative BRCA mutation is not ruled out.

In patients with breast or ovarian cancer who are from high-risk families without a known BRCA1 or BRCA2 gene and who are not from ethnic groups with known founder mutations, comprehensive BRCA mutation analysis should be performed.

Testing in eligible individuals who belong to ethnic populations in which there are well-characterized founder mutations should begin with tests specifically for these mutations. For example, founder mutations account for approximately three quarters of the BRCA mutations found in Ashkenazi Jewish populations (see Rationale). When the testing for founder mutations is negative, comprehensive mutation analysis should then be performed.

Comprehensive mutation analysis includes sequencing the coding regions and intron/exon splice sites as well as tests to detect common large deletions and rearrangements that can be missed with sequence analysis alone. The BRCA Analysis (Large) Rearrangement Test (BART) provides a refined method to detect rare large genomic rearrangements in both BRCA1 and BRCA2 genes. BART testing can be used to identify additional BRCA1 and BRCA2 mutations in women at high-risk for breast cancer who have tested negative for BRCA1 and BRCA2 sequence mutations. Large rearrangement mutations account for 6-10% of all HBOC mutations identified.

Cell cycle checkpoint kinase2 (CHEK2) is also involved with DNA repair and human cancer predisposition like BRCA1 and BRCA2. CHEK2 is normally activated in response to DNA double-stranded breaks or damage. CHEK2 regulates the function of BRCA1 protein in DNA repair and also exerts critical roles in cell cycle control and apoptosis. The CHEK2 deletion-mutation, 1100delC in exon 10 has been associated with an increased risk of familial breast cancers.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

Genetic testing for BRCA1 and BRCA2 mutations for the diagnosis or risk assessment of hereditary breast and/or ovarian cancer (HBOC) may be considered medically necessary under ANY of the following circumstances:

  1. An individual from a family with a known BRCA1 or BRCA2 mutation; or
  2. A personal history of breast cancer (including invasive and ductal carcinoma in situ) AND any of the following (1-9):
    1. Diagnosed at age 45 years or younger;
    2. Diagnosed at age 50 years or younger, with one or more close blood relatives with breast cancer at age 50 years or younger, and/or one or more close blood relatives with epithelial ovarian, fallopian tube or primary peritoneal cancer at any age;
    3. Two primary breast cancers (including bilateral disease or cases where there are two or more clearly separate [ipsilateral] primary tumors) when first breast cancer diagnosis occurred prior to age 50 years;
    4. Diagnosed by age 60 years with triple-negative (ER-, PR-, HER-2) breast cancer;
    5. Diagnosed by age 50 years with a limited family history, such as fewer than two first- or second-degree female blood relatives or female blood relatives surviving beyond 45 years in either lineage;
    6. Diagnosed at any age, with at least two close blood relatives with either breast,   epithelial ovarian, fallopian tube or primary peritoneal cancer at any age;
    7. Close male blood relative with breast cancer;
    8. Personal history of epithelial ovarian, fallopian tube or primary peritoneal cancer;
    9. For an individual of ethnicity associated with higher mutation frequency (known as founder populations of Ashkenazi Jewish, Icelandic, Swedish, Hungarian, or Dutch descent); or
  3. A personal history of either epithelial ovarian, fallopian tube or primary peritoneal cancer; or
  4. A personal history of male breast cancer; or
  5. A personal history of breast and/or ovarian cancer at any age with two or more close blood relatives with pancreatic cancer at any age: or
  6. A personal history of pancreatic cancer at any age with two or more close blood relatives with breast and/or ovarian and/or pancreatic cancer at any age; or
  7. An individual without a personal history, but with a family history of:
    1. A first- or second-degree blood relative who meets any of the high risk criteria specified in A through F above, or
    2. Two third-degree blood relatives or closer with breast cancer (with at least one of the two having breast cancer at 50 years or younger) and/or ovarian cancer.

NOTE: Definitions of close blood relatives, according to the National Comprehensive Cancer Network Guidelines criteria:

  • First-degree relative:  Any relative who is one meiosis away from a particular individual in a family; a relative with whom one-half of an individual’s genes are shared, a 50% genetic link to the patient (i.e., parent, sibling, offspring).
  • Second-degree relative:  Any relative who is two meioses away from a particular individual in a family; a relative with whom one-quarter of an individual's genes are shared, a 25% genetic link to the patient (i.e., grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling).
  • Third-degree relative:  Any relative who is three meioses away from a particular individual in a family; a relative with whom one-eighth of an individual’s genes are shared, a 12.5% genetic link to the patient (i.e., great-grandparent, great-grandchild, great-uncle, great-aunt, grand nephew, grand niece, first cousin).

Testing for genomic rearrangements of the BRCA1 and BRCA2 genes (BRCA Analysis® [Large] Rearrangement Test [BART]) may be considered medically necessary in patients who meet criteria for BRCA mutation testing, whose testing for point mutations is negative and either:

  1. There are three or more family members of one lineage affected with breast, ovarian, fallopian tube, or primary peritoneal cancer; or
  2. There is a risk of a BRCA mutation.

Genetic testing for BRCA1 and BRCA2 mutations for the diagnosis or risk assessment of hereditary breast and/or ovarian cancer (HBOC) is considered experimental, investigational and unproven in any of the following circumstances:

  • As a screening technique for unaffected individuals, who do not have a personal or familial history of breast or ovarian cancer; or
  • As a risk assessment for affected or unaffected individuals, whose family has a history of prostate cancer or melanoma; or
  • Those affected with breast or ovarian cancer, who not meeting any of the above criteria; or
  • In minors, as it is not known how an HBOC mutation would change their medical management.

Testing for cell cycle checkpoint kinase2 (CHEK2) genetic abnormalities (mutations, deletion, etc.) is considered experimental, investigational and unproven in affected and unaffected patients with breast cancer irrespective of their family history.

NOTE: Both maternal and paternal family histories are important, and each lineage must be considered separately.

Rationale

Articles that were published since a 1997 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment were reviewed for information regarding professional guidelines for BRCA (breast cancer genes) testing, testing of unaffected family members, and testing of high-risk ethnic populations. In addition, web sites for relevant professional organizations were consulted for posted guidelines.

The American Society of Clinical Oncology (ASCO) recommends that cancer predisposition testing be offered when (1) the person has a strong family history of cancer or very early age of onset of disease, (2) the test can be adequately interpreted, and (3) the results will influence the medical management of the patient or family member.

In 1999, the American College of Medical Genetics (ACMG) published guidelines for BRCA testing under the auspices of a grant from the New York State Department of Health to the ACMG Foundation. The guidelines suggest that increased risk for a mutation in a known cancer susceptibility gene is evident if:

  • There are three or more affected first or second degree relatives on the same side of the family, regardless of age at diagnosis, or
  • There are fewer than three affected relatives, but
    • the patient was diagnosed at 45 years of age or less, or
    • a family member has been identified with a detectable mutation, or
    • there are one or more cases of ovarian cancer at any age, and one or more members on the same side of the family with breast cancer at any age, or
    • there are multiple primary or bilateral breast cancers in the patient or one family member, or
    • there is breast cancer in a male patient, or in a male relative, or
    • the patient is at increased risk for specific mutation(s) due to ethnic background (for instance: Ashkenazi Jewish descent) and has one or more relatives with breast cancer or ovarian cancer at any age.

Early estimates of lifetime risk of cancer for BRCA mutation carriers (penetrance), based on studies of families with extensive history of disease, have been as high as 85%. Because other factors that influence risk may be present in families with extensive breast or ovarian cancer histories, early penetrance estimates may have been biased upward. Studies of founder mutations in ethnic populations (e.g., Ashkenazi Jewish, Polish, and Icelandic populations) unselected for family history indicated lower penetrance estimates, in the range of 40–60% for BRCA1 (breast cancer 1) and 25–40% for BRCA2 (breast cancer 2). However, a genotyping study of Ashkenazi Jewish women with incident, invasive breast cancer, selected regardless of family history of cancer, and their family members resulted in an 82% lifetime risk of breast cancer for carriers of any of three BRCA founder mutations. Importantly, the risk of cancer in mutation carriers from families with little history of cancer (approximately 50% of all carriers) was not significantly different. Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2 mutation carriers. Women with a history of breast cancer and a BRCA mutation have a significant risk of contralateral breast cancer; in one study the risk was 29.5% at 10 years for women with initially stage I or II disease.

Thus, the risk of cancer in a BRCA mutation carrier is significant, and knowledge of mutation status in individuals at potentially increased risk of a BRCA mutation may impact healthcare decisions to reduce risk. Risk-reducing options include intensive surveillance, prophylactic mastectomy, or prophylactic oophorectomy. Prophylactic mastectomy reduces the risk of breast cancer in high-risk women (based on family history) by 90% or more, but is invasive and disfiguring. Prophylactic oophorectomy significantly reduces the risk of ovarian cancer to less than 10% and reduces the risk of breast cancer by approximately 50%. In women who have already had breast cancer, prophylactic oophorectomy reduces the risk of cancer relapse. Studies indicate that genotyping results significantly influence treatment choices.

The prevalence of BRCA mutations is approximately 0.1–0.2% in the general population. Prevalence may be much higher for particular ethnic groups with characterized founder mutations (e.g., 2.5% [1 in 40] in the Ashkenazi Jewish population). Family history of breast or ovarian cancer is an important risk factor for BRCA mutation. Age and, in some cases, ethnic background can also be independent risk factors.

Young age of onset of breast cancer, even in the absence of family history, has been demonstrated to be a risk factor for BRCA1 mutations. Winchester estimated that hereditary breast cancer accounts for 36%–85% of patients diagnosed under age 30. In several studies, BRCA mutations are independently predicted by early age at onset, being present in 6–10% of breast cancer cases diagnosed at ages younger than various premenopausal age cutoffs (ages 35–50 years). In cancer-prone families, the mean age of breast cancer diagnosis among women carrying BRCA1 or BRCA2 mutations is in the 40s. In the Ashkenazi Jewish population, Frank et al. reported BRCA mutations in 13% of 248 cases with no known family history and diagnosed before 50 years of age. In a similar study, 31% of Ashkenazi Jewish women, unselected for family history, diagnosed with breast cancer at younger than 42 years of age had BRCA mutations. Additional studies indicate that early age of breast cancer diagnosis is a significant predictor of BRCA mutations in the absence of family history in this population.

As in the general population, family history of breast or ovarian cancer, particularly of early age onset, is a significant risk factor for a BRCA mutation in ethnic populations characterized by founder mutations. For example, in unaffected individuals of Ashkenazi Jewish descent, 12–31% will have a BRCA mutation depending on the extent and nature of the family history. Several other studies document the significant influence of family history.

Unaffected individuals with a family history suggestive of HBOC but unknown family mutation may obtain interpretable results in most cases of a positive test. Most BRCA1 and BRCA2 mutations reported to date consist of frameshift deletions, insertions, or nonsense mutations leading to premature truncation of protein transcription. These are invariably deleterious and thus are informative in the absence of an established familial mutation. In addition, specific missense mutations and noncoding intervening sequence mutations may be interpreted as deleterious on the basis of accumulated data or from specific functional or biochemical studies. However, some BRCA mutations may have uncertain significance in the absence of a family study, and negative results offer no useful information, i.e., the patient may still be at increased risk of a disease-associated mutation in an as yet undiscovered gene.

This policy was updated with a literature review using MedLine in January 2008. While the ASCO and ACMG guidelines noted above have not been updated, new guidelines for breast or ovarian cancer susceptibility have been published by the U.S. Preventive Services Task Force (USPSTF) and the National Comprehensive Cancer Network (NCCN). The USPSTF review includes summary of criteria from various groups on genetic testing in this situation. These guidelines help to better define families where there is a “high risk of a mutation” and also provide information about testing both for men with breast cancer and for women with ovarian cancer.

A clinical approach to these patients was recently published by Robson and Offit. Phillips reported that while uptake of prophylactic surgery and screening was associated with knowing one’s mutation status, in their cohort of 70 unaffected female mutation carriers who had chosen to receive results, the minority utilized risk-reducing surgery (11% had bilateral mastectomy and 29% bilateral oophorectomy) or chemoprevention. Rennert and colleagues reported that breast cancer-specific rates of death among Israeli women were similar for carriers of a BRCA founder mutation and noncarriers. Malone and colleagues reported on racial and ethnic differences in the prevalence of BRCA1 and BRCA2 in American women. Among their cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in “white” (2.9%) versus “black” (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in “black” (2.6%) versus “white” (2.1%) cases. Couch et al. studied familial pancreatic cancer and noted that BRCA2 mutations accounted for 6% of moderate and high-risk pancreatic cancer families.

Using information from the USPSTF, a family at high-risk of having a mutation is determined by having any of the following characteristics: three or more first- or second-degree relatives with breast cancer regardless of age at diagnosis; or two first-degree relatives with breast cancer, one of whom was diagnosed at age 50 years or younger; or combination of both breast and ovarian cancer among first- and second-degree relatives; or first-degree relative with bilateral breast cancer; or a combination of two or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis; or a first- or second-degree relative with both breast and ovarian cancer at any age; or a history of breast cancer in a male relative. In addition, based on information in the NCCN guidelines and in recognition of changes in management (including mammography) that can occur in males with, or at high-risk for, breast cancer, testing males affected by breast cancer was added to the policy statement.

In applying this policy, an accurate family history is a key component in deciding which patients will be tested. In interpreting this history, it is important to evaluate the maternal and paternal lineage separately.

Finally, one of the policy statements indicates that this testing is experimental, investigational and unproven in minors, because there is no change in management for minors as a result of knowledge of the presence or absence of a deleterious mutation. In addition, there are potential harms related to stigmatization and discrimination.

2011 Update

Testing for BRCA1 and BRCA2

The medical policy update was based upon a review of the published 2011 NCCN Guidelines criteria of genetic or familial high-risk assessment of breast and ovarian cancer. According to the Guidelines: “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, full sequencing of the genes is usually performed. For individuals with family histories consistent with a pattern of HBOC 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. The testing of unaffected family members may be considered when there is no known deleterious mutation in the family and no affected member is available. A negative test result in this case, 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 the case of HBOC (i.e., BRCA mutation), if no family member with breast or ovarian cancer is living, consideration can be given to testing first- or second-degree family members affected with cancers thought to be related to the deleterious mutation in question (e.g., prostate or pancreatic cancer).” 

NCCN reports that some histopathological features occur in breast cancer mutations, such as in the BRCA1 mutation of ER-, PR-, and HER-2 “triple-negative” breast cancer characterization. The studies reveal, “BRCA 1 mutations in 11% to 28% of patients with triple-negative breast cancer. In addition, it appears that among patients with triple-negative disease, BRCA mutation carriers were diagnosed at a younger age compared with non-carriers.” In fact a study of 284 patients demonstrated the mean age of diagnosis was 40 years in carriers of BRCA1 with triple-negative breast cancer. Interestingly, those patients with early onset of triple-negative disease, diagnosed at 40 years or younger, were shown to have the BRCA1 mutation.

There are reports of other malignancy types in families with a BRCA1 or BRCA2 gene mutation, such as prostate cancer and melanoma, however there are no known studies. BRCA1 or BRCA2 screening for risk assessment of HBOC when there is a family history of prostate cancer or melanoma has not been recommended by the NCCN.

In addition to the NCCN statement above, the NCCN Guidelines recommend BRCA testing for those individuals with a personal history of male breast cancer, a personal history of epithelial ovarian, fallopian tube or primary peritoneal cancer (particularly suspicious when there is an early onset), or when the patient is a member of a family with a known deleterious BRCA1 or BRCA2 mutation (such as coming from a founder population). Generally, individuals of Ashkenazi Jewish descent are considered a founder population; however, full-sequencing may be considered if the individual’s ancestry also includes non-Ashkenazi Jewish relative or HBOC criteria. Examples of other founder populations within an individual’s ancestry include Icelandic, Swedish, Hungarian, and Dutch. The NCCN Guidelines maintain when investigating genetic family histories, the maternal and paternal sides should be considered independently. Close relatives should be considered as first-, second-, and third-degree relatives. Since the NCCN Guidelines are derived from a uniform consensus, the recommendation is categorized as level 2A strength of evidence that indicates BRCA mutation testing is appropriate for a specific subset of individuals who are at high-risk for HBOCs.

Testing for Large BRCA Rearrangements (BRCA Analysis Rearrangement Test [BART])

Over the past few years, a number of studies have shown that a significant percentage of women with a strong family history of breast cancer and negative tests for BRCA mutations have large genomic rearrangements (including deletions or duplications) in one of these genes. For example, in 2006 Walsh and colleagues reported on probands from 300 U.S. families with four or more cases of breast or ovarian cancer but with negative (wild-type) commercial genetic tests for BRCA1 and BRCA2. These patients underwent screening with additional multiple DNA-based and RNA-based methods. Of these 300 patients, 17% carried previously undetected mutations, including 35 (12%) with genomic rearrangement of BRCA1 or BRCA2.

A more recent study evaluated 251 patients with an estimated BRCA mutation using the Myriad II model of 10% or greater. In the 136 non-Ashkenazi Jewish probands, 36 (26%) had BRCA point mutations and eight (6%) had genomic rearrangements, seven in BRCA1 and one in BRCA2. No genomic rearrangements were identified in the 115 Ashkenazi Jewish probands, but 47 of the 115 (40%) had point mutations. In this population genomic rearrangements constituted 18% of all identified BRCA mutations. The authors also indicated that the estimated prevalence of a mutation was not predictive of the presence of a genomic rearrangement.

Thus, based on these published studies, testing for genomic rearrangements of BRCA1 and BRCA2 may be considered medically necessary when testing for standard mutations is negative in familial breast cancer when (1) there are three or more family members in one lineage affected with breast or ovarian or fallopian tube or primary peritoneal cancer, or (2) in individuals with a risk of a BRCA mutation of at least 10%. The threshold of three or more family members (instead of four or more) was selected because of concerns raised by the impact of having a small number of offspring.

Commercial laboratories, such as Myriad’s BART technology, began this expanded testing in August 2006; BRCA testing before then did not include analysis for genomic rearrangement. After 2006, additional rearrangement testing is conducted on the subset of patients whose likelihood of a BRCA mutation is 30% or greater. When the likelihood of a BRCA mutation is between 10% and 30%, the test for genomic rearrangement must be ordered separately.

Testing for CHEK2 Mutations

A number of publications have also described the association of CHEK2 (cell cycle checkpoint kinase 2) mutations with hereditary breast cancer. The prevalence of this finding varies greatly by geographic regions, being most common in northern and eastern Europe. It has been detected in 4% of early breast cancer patients in the Netherlands, in 2.3% of such patients in Germany, but has been noted to be rare in these patients in Spain or Australia. In the U.S., this mutation is much less common than BRCA mutations and BRCA rearrangements. For example, in the study by Walsh cited above, 14 (4.7%) of the 300 patients with a positive family history of breast cancer (four affected relatives), who were negative by standard BRCA testing, were positive for CHEK2 mutations. The low frequency makes evaluation of risk and treatment implications less precise. In general, the risk of breast cancer associated with this mutation is less than that associated with either BRCA1 or BRCA2.

A meta-analysis by Weischer concluded that for familial breast cancer, the cumulative risk at age 70 years for CHEK2 1100delC mutation was 37% (confidence interval 26% to 56%). This risk is lower than cumulative risk at age 70 of 57% for BRCA1 and 49% for BRCA2. In particular, they raise questions about the breast cancer risk estimates presented in the Weischer study; a number of the questions relate to the variable methods of ascertainment used in the studies in this meta-analysis. They also note that other mutations, such as CHEK2 S428F, are observed in other populations. The varying frequency is mentioned, with the mutation noted in 0.5 – 1.0% of the population in northern and eastern Europe compared with 0.2 – 0.3% in the U.S. Finally, they raise concerns about the implications of the low penetrance of this mutation. They concluded that on the basis of data available at this time, there is not compelling evidence to justify routine clinical testing for CHEK2 to guide the management of families affected with breast cancer. Thus, based on a number of concerns, testing for CHEK2 mutations is considered experimental, investigational and unproven because the impact on net health outcome is uncertain.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

ICD-9 Codes

158.0, 158.8, 158.9, 174.0, 174.1, 174.2, 174.3, 174.4, 174.5, 174.6, 174.8, 174.9, 175.0, 175.9, 183.0, 183.2, 198.6, 198.81, 233.0, 233.30, 233.39, 238.3, 239.3, V10.3, V10.43, V10.44, V16.3, V16.41, V16.49, V16.8, V82.71, V82.79, V84.01, V84.02, V84.09

ICD-10 Codes

C45.1, C48.0, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.111, C50.112, C50.119, C50.211, C50.212, C50.219, C50.311, C50.312, C50.319, C50.411, C50.412, C50.419, C50.511, C50.512, C50.519, C50.611, C50.612, C50.619, C50.811, C50.812, C50.819, C50.911, C50.912, C50.919, C50.021, C50.022, C50.029, C50.121, C50.122, C50.129, C50.221, C50.222, C50.229, C50.321, C50.322, C50.329, C50.421, C50.422, C50.429, C50.521, C50.522, C50.529, C50.621, C50.622, C50.629, C50.821, C50.822, C50.829, C50.921, C50.922, C50.929, C56.1, C56.2, C56.9, C57.0, C57.01, C57.02, C79.60, C79.61, C79.62, C79.81, D05.00, D05.01, D05.02, D05.10, D05.11, D05.12, D05.80, D05.81, D05.82, D05.90, D05.91, D05.92, D07.30, D07.39, D48.60, D48.61, D48.62, D49.3, Z13.71, Z13.79, Z13.89, Z15.01, Z15.02, Z153.09, Z80.3, Z80.41, Z80.8, Z85.3, Z85.43

Procedural Codes: 81211, 81212, 81213, 81214, 81215, 81216, 81217
References
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  20. Gershoni-Baruch, R., Dagan, E., et al. Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer. European Journal of Cancer (2000 May) 36(8):983-6.
  21. Boyd, J., Sonoda, Y., et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. Journal of the American Medical Association (2000 May 3) 283(17):2260-5.
  22. Huang, L.W., Garrett, A.P., et al. Distinct allelic loss patterns in papillary serous carcinoma of the peritoneum. American Journal of Clinical Pathology (2000 July) 114(1):93-9.
  23. Risch, H.A., McLaughlin, J.R., et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. American Journal of Human Genetics (2001 March) 68(3):700-10.
  24. Satagopan, J.M., Offit, K., et al. The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiology, Biomarkers and Prevention (2001 May) 10(5):467-73.
  25. Moller, P., Borg, A., et al. Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy. N International Journal of Cancer (2002 October 20) 101(6):555-9.
  26. Runnebaum, I.B., Wang-Gohrke, S., Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics (2001 October) 11(7):635-8.
  27. Altaras, M.M., Bernheim, J., et al. Papillary serous carcinoma of the peritoneum coexisting with or after endometrial carcinoma. Gynecologic Oncology (2002 February) 84(2):245-51.
  28. Rebbeck, T.R., Lynch, H.T., et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. New England Journal of Medicine (2002 May 23) 346(21):1616-22.
  29. Scheuer, L., Kauff, N., et al. Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. Journal of Clinical Oncology (2002 March 1) 20(5):1260-8.
  30. Frank, T.S., Deffenbaugh, A.M., et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. Journal of Clinical Oncology (2002 March 15) 20(6):1480-90.
  31. Begg, C.B. On the use of familial aggregation in population-based case probands for calculating penetrance. Journal of the National Cancer Institute (2002 August 21) 94(16):1221-6.
  32. Weitzel, J.N., McCaffrey, S.M., et al. Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Archives of Surgery (2003 December) 138(12):1323-8.
  33. King, M.C., Marks, J.H., et al. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science (2003 October 24) 302(5645):643-6.
  34. ASCO – American Society of Clinical Oncology: Policy Statement Update: Genetic Testing for Cancer Susceptibility (2003 March 1). Available at http://www.asco.org (accessed 2008 February 8).
  35. Domchek, S.M., Eisen, A., et al. Application of breast cancer risk prediction models in clinical practice. Journal of Clinical Oncology (2003 February 15) 21(4):593-601.
  36. Menkiszak, J., Rzepka-Gorska, I., et al. Attitudes toward preventive oophorectomy among BRCA1 mutation carriers in Poland. European Journal of Gynaecological Oncology (2004) 25(1):93-5.
  37. Casey, M.J., and C. Bewtra. Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations. Familial Cancer (2004) 3(3-4):265-81.
  38. Olopade, O.I., and G. Artioli. Efficacy of risk-reducing salpingo-oophorectomy in women with BRCA-1 and BRCA-2 mutations. Breast Journal (2004 January-February) 10(supplement 1):S5-9.
  39. Metcalfe, K., Lynch, H.T., et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of Clinical Oncology (2004 June 15) 22(12):2328-35.
  40. Narod, S.A., and W.D. Foulkes. BRCA1 and BRCA2: 1994 and beyond. National Review Cancer (2004 September) 4(9):665-76.
  41. USPSTF – U.S. Preventive Services Task Force: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement (2005). Available at www.ahrq.gov (accessed 2008 February 8).
  42. Meewissen, P.A., Seynaeve, C., et al. Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer. Gynecologic Oncology (2005 May) 97(2):476-82.
  43. Nelson, H.D., Huffman, L.H., et al. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force. Annals of Internal Medicine (2005 September 6) 143:362-79. (Also available at http://www.ahrq.gov .)
  44. Pal, T., Permuth-Wey, J., et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer (2005 December 15) 104(12):2807-16.
  45. Walsh, T., Casadei, S., et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. Journal of the American Medical Association (2006 March 22) 295(12):1379-88.
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History
March 2011 Policy updated with literature search, description, references and rationale sections revised. Two policy statements were added: one to indicate testing for genomic rearrangements may be considered medically necessary in specific situations and a second that testing for CHEK2 mutations is investigational. Fallopian tube cancer and primary peritoneal cancer added to policy statements and policy guidelines as additional cancers to be assessed in determining family history to assess risk. Denial reason changed from "not medically necessary" to "Investigational."
March 2012 Policy updated with literature review; references 32-40 and 46-48 added. Policy statement on CHEK2 testing amended to read: “Testing for mutations other than BRCA1 and BRCA2, such as the CHEK2 abnormality (mutations, deletions, etc.) is considered investigational in affected and unaffected patients with breast cancer, irrespective of the family history.”CPT codes 81211, 81212, 81213, 81214, 81215, 81216, 81217 Added to policy.
July 2013 Removed the following criteria from the Medically Necessary statement on BART testing: "(1) there are 3 or more family members (one lineage) affected with breast or ovarian or fallopian tube or primary peritoneal cancer or (2) who have a risk of a BRCA mutation of at least 10%".
October 2013 Policy formatting and language revised.  Title changed from "Genetic Testing for Hereditary Breast and/or Ovarian Cancer (BRCA1 or BRCA2 Mutations)" to "Genetic Testing for Hereditary Breast and/or Ovarian Cancer (HBOC)".  Added additional clinical scenarios for coverage for BART testing.
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Genetic Testing for Hereditary Breast and/or Ovarian Cancer (HBOC)