Medical Policy: 02.04.74 

Original Effective Date: August 2018 

Reviewed: August 2020 

Revised: August 2020 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

This policy focuses on testing of BRCA mutation status. This testing may be completed as a test for cancer susceptibility or in tumor/tissue of an individual with a current cancer diagnosis.

 

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of each cell’s genetic material. When either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

 

Harmful BRCA1 and BRCA2 gene mutations are relatively rare in the general population, most experts agree that mutation testing of individuals who do not have cancer should be performed only when the person’s individual or family history suggests the possible presence of a harmful mutation in BRCA1 or BRCA2. Genetic testing is only recommended for people with a high risk of having a BRCA mutation.

 

Risk scales used to determine need for genetic testing:
Ontario Family History Assessment Tool
Risk Factor Points
Breast and ovarian cancer
Mother 10
Sibling 7
Second-/third-degree relative 5
Breast cancer relatives
Parent 4
Sibling 3
Second-/third-degree relative 2
Male relative (add to above) 2
Breast cancer characteristics
Onset age, y
20-29 6
30-39 4
40-49 2
Premenopausal/perimenopausal 2
Bilateral/multifocal 3
Ovarian cancer relatives
Mother 7
Sibling 4
Second-/third-degree relative 3
Ovarian cancer onset age, y
<40 6
40-60 4
>60 2
Prostate cancer onset
Age <50 y 1
Colon cancer onset
Age <50 y 1
Family total
Referral ≥10
  
Referral Screening Tool
(referral if 2 or more)
History of Breast or Ovarian Cancer in the Family? If Yes, Complete Checklist
Risk Factor Breast Cancer at Age ≤50 y Ovarian Cancer at any Age
Yourself   
Mother   
Sister   
Daughter   
Mother’s side   
Grandmother   
Aunt   
Father’s side   
Grandmother   
Aunt   
≥2 cases of breast cancer after age 50 y on same side of family   
Male breast cancer at any age in any relative   
Jewish ancestry   
 
Pedigree Assessment Tool
(score 8 or greater is the optimal referral threshold)
Risk Factor Score for Every Family Member with Breast or Ovarian Cancer Diagnosis, Including Second-/Third-Degree Relatives
Breast cancer at age ≥50 y 3
Breast cancer at age <50 y 4
Ovarian cancer at any age 5
Male breast cancer at any age 8
Ashkenazi Jewish heritage 4
Total (score 8 or greater is the optimal referral threshold)

 
Seven-Question Family History Screening
(One positive response initiates referral)

  1. Did any of your first-degree relatives have breast or ovarian cancer?
  2. Did any of your relatives have bilateral breast cancer?
  3. Did any man in your family have breast cancer?
  4. Did any woman in your family have breast and ovarian cancer?
  5. Did any woman in your family have breast cancer before age 50 y?
  6. Do you have 2 or more relatives with breast and/or ovarian cancer?
  7. Do you have 2 or more relatives with breast and/or bowel cancer?

 

International Breast Cancer Intervention Study Model (also known as Tyrer-Cuzick)
(Referral for genetic testing if the personal risk level for a mutation in breast cancer susceptibility gene 1 or 2 is 10% or greater)
Risk Factor

  1. Personal history: current age, age at menopause, age at menarche, childbirth history, menopausal status, use of menopausal hormone therapy
  2. Personal breast history, breast density (optional), prior breast biopsy, history of cancer (breast or ovarian), genetic testing
  3. Ashkenazi Jewish inheritance
  4. Family history (genetic risk) – relatives with breast or ovarian cancer, age at diagnosis, genetic testing

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

National Comprehensive Cancer Network (NCCN) guidelines present specific criteria for genetic testing for hereditary breast and/or ovarian cancer syndrome. The guidelines address genetic risk assessment, counseling, testing and management based on test results.

 

The current National Comprehensive Cancer Network (NCCN) guideline (Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 3.2019) states that a male warrants genetic counseling and to consider genetic testing if he has metastatic prostate cancer or prostate cancer (any grade) with the following: (1) at least one close blood relative with ovarian cancer or breast cancer at age 50 or younger, or (2) at least two relatives with breast, ovarian, or prostate cancers (Gleason 7 or higher) at any age. Testing with a diagnosis of non-metastatic or intraductal prostate cancer without the family history component is not recommended.

 

The current National Comprehensive Cancer Network (NCCN) guideline Pancreatic Adenocarcinoma (Version 1.2020) recommends specific regimens based on BRCA 1/2 mutations. Poly (ADP-ribose) polymerase (PARP) inhibitor therapy: The NCCN guideline for pancreatic adenocarcinoma considers the use of olaparib as maintenance therapy for individuals with a germline BRCA 1/2 mutation, with no progression of disease after at least 4-6 months of chemotherapy, assuming acceptable tolerance

 

At this time no other NCCN guidelines recommend the genetic testing of BRCA1 or BRCA2 based on diagnosis alone. 

 

American Society of Clinical Oncology (ASCO)

An ASCO policy statement recommends that genetic testing for cancer susceptibility be performed when the following three criteria are met: the individual being tested has a personal or family history suggestive of genetic cancer susceptibility; the test can be adequately interpreted; and the test results have accepted clinical utility.

 

American Society of Breast Surgeons

American Society of Breast Surgeons (2019): The Society published a consensus document regarding genetic testing for hereditary breast cancer. Recommendations include:

  • Breast surgeons, genetic counselors, and other medical professionals knowledgeable in genetic testing can provide patient education and counseling and make recommendations to their patients regarding genetic testing and arrange testing.
  • Genetic testing should be made available to all patients with a personal history of breast cancer.
  • Patients who had genetic testing previously may benefit from updated testing
  • Genetic testing should be made available to patients without a history of breast cancer who meet NCCN guidelines
  • Variants of uncertain significance are DNA sequences that are NOT clinically actionable. 

 

United States Preventative Services Task Force (USPSTF)

USPSTF guidelines recommend screening women with any family history of breast, ovarian, tubal, or peritoneal cancer. Women with positive screening results should receive genetic counseling and, if indicated after counseling, BRCA testing. (Grade B Recommendation; Recommended). USPSTF recommends against routine genetic counseling or BRCA testing for those whose family history is not associated with an increased risk for potentially harmful mutations in the BRCA1or BRCA2 gene. (Grade D recommendation; Not recommended).

 

The USPSTF guidelines no longer make explicit recommendations as to who should have BRCA1/2 gene testing; they specifically make recommendations for genetic counseling. In general, women identified as high risk by these screening tools have one or more of the following characteristics:

  • a first or second-degree relative with breast cancer before 50 years old
  • a first or second-degree relative with ovarian cancer
  • a first or second-degree relative with bilateral/multifocal breast cancer
  • a first- or second-degree male relative with breast cancer
  • a first or second degree relative with both breast and ovarian cancers
  • two or more relatives, first, second, third degree, with breast or ovarian cancer
  • two or more relatives, first, second, third degree, with breast or prostate/pancreatic cancer, or
  • presence of Ashkenazi Jewish ancestry with any of the above. 

 

Professional societies do not recommend that children under age 18, even those with a family history suggestive of a harmful BRCA1 or BRCA2 mutation, undergo genetic testing for BRCA1 or BRCA2 This is because there are no risk-reduction strategies that are specifically meant for children, and children's risks of developing a cancer type associated with a BRCA1 or BRCA2 mutation are extremely low.

 

Regulatory Status

Numerous BRCA tests are available as listed below. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of these:

  • Myriad Genetic Laboratories offers the following tests:
    • Comprehensive BRACAnalysis® test includes complete sequencing of BRCA1 and BRCA2 and gap polymerase chain reaction for five common rearrangements (deletions, duplications) in BRCA1
    • BRACAnalysis® Large Rearrangement Test (BART™) is a reflex test for patients who test negative on the Comprehensive BRACAnalysis® test to detect uncommon large rearrangements in BRCA1 and BRCA2
    • Integrated BRACAnalysis® test includes BART™ as part of BRCA1 or BRCA2 analysis
    • BRACAnalysis CDxs® is intended to detect germline BRCA1 and BRCA2 variants to identify patients with breast or ovarian cancer who may be considered for treatment with olaparib, niraparib, or talazoparib.
  • Quest Diagnostics offers BRCAvantage™, which includes sequencing of BRCA1 and BRCA2 and a multiplex ligation-dependent probe amplification assay to detect both common and uncommon gene rearrangements.
  • LabCorp offers the BRCAssureSM suite of tests, which includes: targeted BRCA1 and BRCA2 variant analysis; a founder mutation panel for Ashkenazi Jewish patients (three variants); comprehensive BRCA1 and BRCA2 analysis (full gene sequencing plus analysis of common and uncommon large rearrangements); and deletion and duplication analysis of uncommon large rearrangements only (without sequencing) when comprehensive analysis is negative.

 

Prior Approval:

Prior Approval is required.

 

Policy:

For additional information see the following policies.

 

For panel testing for inherited cancer susceptibility see policy: Expanded Genetic Panels to Identify Cancer Risk 02.04.64

 

For panel testing of an individual with a cancer diagnosis see policy: Expanded Genetic Panels to Identify Targeted Cancer Therapy 02.04.63

 

Genetic testing of BRCA1 and BRCA2 for breast cancer, ovarian cancers, hereditary breast and ovarian cancer syndrome (HBOC) or in those with Ashkenazi Jewish ethnicity is not addressed in this policy.

 

Hereditary breast and ovarian cancer (HBOC) is an inherited form of cancer characterized by:

  • Personal history of breast cancer at a young age (typically under age 50)
  • Personal history of two primary breast cancers
  • Personal history of both breast and ovarian cancer
  • Personal history of a triple negative breast cancer (ER-, PR-, HER2-)
  • Personal history of ovarian/fallopian tube/primary peritoneal cancer
  • Personal history of metastatic prostate cancer
  • Multiple cases of breast and/or ovarian cancer in a family
  • Personal or family history of male breast cancer
  • Personal or family history of pancreatic cancer with breast or ovarian cancer
  • Personal or family history of prostate cancer with a Gleason score of at least 7 and a family history of ovarian, breast, prostate, or pancreatic cancer
  • Previously identified BRCA1/2 mutation in the family
  • Any of the above with Ashkenazi Jewish ancestry

 

Genetic Testing In Children

Genetic testing of BRCA in those under 18 years old is considered not medically necessary.

 

Genetic Testing outside of  breast cancer, ovarian cancers, hereditary breast and ovarian cancer syndrome (HBOC) or in those with Ashkenazi Jewish ethnicity

 

Genetic testing for BRCA mutation/variants for all other indications not managed in breast/ovarian or HBOC cancer, including but not limited to the following, is considered investigational.

  • Gastrointestinal Cancers
  • Laryngeal Cancer
  • Lynch Syndrome
  • Cowden Syndrome
  • Li Fraumeni Syndrome
  • Melanoma
  • Myeloproliferative disease
  • Non-Metastatic Prostate Cancer
  • Blood Cancers
  • Colon cancer 

 

Further evidence is needed to establish the clinical utility of testing in populations outside of indications for breast cancer, ovarian cancers, fallopian tube cancer, pancreatic cancers, Ashkenazi Jewish ethnicity, primary peritoneal, metastatic prostate and HBOC risk. Tests are frequently conducted solely as informational; this will not alter medical management of the patient therefore testing currently lacks clinical utility and does not demonstrate improved net health outcomes. The outcome of the test must be expected to determine a covered course of treatment. Those with BRCA variants have an increased risk of prostate cancer, and patients with known BRCA variants may, therefore, consider more aggressive screening approaches for prostate cancer. However, the presence of non-metastatic prostate cancer in an individual, is not itself considered sufficient justification for BRCA testing. Frequently, the current health status in combination with family history determines the medical necessity of genetic testing.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

  • 81162 BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and full duplication/deletion analysis
  • 81163 BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis
  • 81164 BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (ie, detection of large gene rearrangements)
  • 81165 BRCA1 (BRCA1, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis
  • 81166 BRCA1 (BRCA1, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (ie, detection of large gene rearrangements)
  • 81167 BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (ie, detection of large gene rearrangements)
  • 81212 BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) gene analysis; 185delAG, 5385insC, 6174delT variants
  • 81215 BRCA1 (BRCA1, DNA repari associated) (eg, hereditary breast and ovarian cancer) gene analysis; known familial variant
  • 81216 BRCA2 (BRCA2, DNA repari associated) (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
  • 81307 PALB2 (partner and localizer of BRCA2) (eg, breast and pancreatic cancer) gene analysis; full gene sequence
  • 81308 PALB2 (partner and localizer of BRCA2) (eg, breast and pancreatic cancer) gene analysis; known familial variant
  • 81432 Hereditary breast cancer-related disorders (e.g., 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 (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11
  • 0129U Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, and TP53)
  • 0172U Oncology (solid tumor as indicated by the label), somatic mutation analysis of BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) and analysis of homologous recombination deficiency pathways, DNA, formalin-fixed paraffin-embedded tissue, algorithm quantifying tumor genomic instability score

 

Selected References:

  • Leongamornlert D, Mahmud N, Tymrakiewicz M, Saunders E, Dadaev T, Castro E, Goh C, Govindasami K, Guy M, O'Brien L, Sawyer E, Hall A, Wilkinson R, Easton D, Collaborators UKGPCS, Goldgar D, Eeles R, Kote-Jarai Z. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 2012;106:1697–701.
  • Gallagher DJ, Gaudet MM, Pal P, Kirchhoff T, Balistreri L, Vora K, Bhatia J, Stadler Z, Fine SW, Reuter V, Zelefsky M, Morris MJ, Scher HI, Klein RJ, Norton L, Eastham JA, Scardino PT, Robson ME, Offit K. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res. 2010;16:2115–21.
  • Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2016 Dec 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.  
  • Thorlacius S, Struewing JP, Hartge P, et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet. Oct 24 1998;352(9137):1337-1339. PMID 9802270
  • Lancaster JM, Powell CB, Chen LM, et al. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. Jan 2015;136(1):3-7. PMID 25238946
  • Moyer VA. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. Feb 18 2014;160(4):271-281. PMID 24366376
  • NCCN Guideline Genetic/Familial High-Risk Assessment: Colorectal Version 01.2020  
  • NCCN Guideline Prostate Cancer Version 02.2020 
  • NCCN Guideline Genetic/Familial High-Risk Assessment: Prostate Cancer Early Detection Version 01.2020 
  • NCCN Guideline Genetic/Familial High-Risk Assessment: Breast and Ovarian Version 01.2020 
  • NCCN Guideline Pancreatic Adenocarcinoma Version 01.2020  
  • NCCN Guideline Cutaneous Melanoma 03.2020
  • NCCN Guideline Myeloproliferative Neoplasms Version 01.2020
  • National Institute for Health and Care Excellence (NICE). (June, 2013 last update March 2017). Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. 
  • National Cancer Institute (2018) BRCA Mutations: Cancer Risk and Genetic Testing. 
  • ECRI Institute. Genetic testing for BRCA1 and BRCA2 Mutations for Assessing Pancreatic Cancer Risk. Plymouth Meeting (PA): ECRI Institute; 2010 Dec 9. 7p. [ECRI hotline response].
  • American Society of Breast Surgeons. Consensus guideline on genetic testing for hereditary breast cancer. © 2019 American Society of Breast Surgeons. 
  • Genetics Home Reference. US National Library of Medicine.
  • Pal T, Agnese D, Daly M, et al. Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019 Dec 13. doi: 10.1038/s41436-019-0712-x. [Epub ahead of print].

 

 

Policy History:

  • August 2020 - Annual Review, Policy Revised
  • August 2019 - Annual Review, Policy Revised
  • August 2018 - New Policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.