POLICY: PG0067 ORIGINAL EFFECTIVE: 07/30/02 LAST REVIEW: 01/25/18 MEDICAL POLICY Genetic Testing for Breast and Ovarian Cancers GUIDELINES This policy does not certify benefits or authorization of benefits, which is designated by each individual policyholder contract. Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy and adherence to accepted national standards. This guideline is solely for explaining correct procedure reporting and does not imply coverage and reimbursement. DESCRIPTION Among women, breast cancer is the most commonly diagnosed cancer after non-melanoma skin cancer and is the second leading cause of cancer death after lung cancer. Ovarian cancer is the ninth most common cancer and is noted to be the fifth most deadly. Epithelial ovarian cancer, which is cancer that begins in the cells on the surface of the ovary, comprises the majority of malignant ovarian neoplasm. Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and its fifth most common cause of cancer mortality in women. BRCA testing is to detect mutation in BRCA1 and BRCA2, the two genes associated with most cases of familial breast cancer. Testing is performed to determine whether an individual has inherited a mutated version of the gene. Inheriting a mutation places a woman at very high risk of developing breast cancer and, for BRCA1, ovarian cancer or cancer of the peritoneum. For a man, it means the possibility of passing the mutated gene on to children and in some cases an increased risk of either male breast cancer or other malignancies. BRACAnalysis Rearrangement Test (BART) (Myriad Genetic Laboratories, Inc., Salt Lake City, UT) is utilized to detect rare, large rearrangements of DNA in the BRCA1 and BRCA2 genes. It is intended for use only in individuals at an exceptionally high risk for breast cancer who have previously tested negative for sequence mutations and common large rearrangements on Myriad Genetics standard BRACAnalysis test. On December 19, 2014, the Food and Drug Administration (FDA) approved Lynparza (olaparib; AstraZeneca) for the treatment of advanced ovarian cancer in patients who have previously been treated with 3 lines of chemotherapy and who test positive with the BRACAnalysis CDx test (Myriad Genetics Inc.). The BRACAnalysis CDx test, also FDA approved on December 19, 2014, is a test for deleterious or suspected deleterious germline BRCA mutation, and is intended as an aid in identifying ovarian cancer patients eligible for treatment with Lynparza. 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. 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. POLICY BRCA & BART Testing, including BRACAnalysis CDx, requires prior authorization for all product lines. Code 81433 is non-covered for HMO, PPO, Individual Marketplace, & Elite. Code 81433 requires prior authorization for Advantage. Multigene panels (including next-generation sequencing [NGS]) for hereditary cancer susceptibility require prior authorization for Elite. Multigene panels (including next-generation sequencing [NGS]) for hereditary cancer susceptibility are non-covered for HMO, PPO, Individual Marketplace, & Advantage. These tests include, but may not be limited to, the following:
- 2 - BRCAplus BRCAvantage Plus BreastNext BreastTrue High Risk Panel BREVAGen Invitae Breast Cancer High-Risk Panel myrisk Hereditary Cancer OvaNext OncoVue Breast Cancer Risk Test BRCA & BART Testing, including BRACAnalysis CDx, may be covered with prior authorization. Paramount utilizes InterQual criteria sets for medical necessity determinations. Evidence supports the use of diagnostic testing for BRCA1 and BRCA2 mutations for: Individuals in families in which a known deleterious mutation is present Individuals with breast and/or ovarian cancer who are members of families in which the frequency and distribution of breast and ovarian cancer suggests a pattern of autosomal dominant inheritance Individuals with ovarian cancer, regardless of age at diagnosis or family history of disease Individuals diagnosed at a young age Male individuals diagnosed with breast cancer Individuals diagnosed with two primary tumors Individuals diagnosed with breast and/or ovarian cancer who are of Ashkenazi Jewish descent Individuals less than age 40 with estrogen receptor (ER) negative, progesterone receptor (PR)negative, and HER2 negative breast cancer Consultants agree that criteria for testing in individuals of Ashkenazi Jewish descent are less stringent that for those who are not of Ashkenazi Jewish descent In some cases, individuals diagnosed with breast and/or ovarian cancers who have a limited family structure (defined as having fewer than two first or second degree female relatives in each lineage) may be candidates for testing Evidence supports the use of predictive testing for BRCA1 and BRCA2 mutations for: Individuals in families in which a known deleterious mutation is present Individuals who are members of families in which the frequency and distribution of breast and ovarian cancer suggests a pattern of autosomal dominant inheritance Consultants agree that criteria for testing in individuals of Ashkenazi Jewish descent are less stringent than for those who are not of Ashkenazi Jewish descent Individuals with male relative(s) diagnosed with breast cancer Males who are undergoing testing in order to provide information on a family member s mutation status Genetic counseling before and after BRCA-related testing is evidence supported. Paramount considers BRCA testing (e.g., BRACAnalysis CDx) (81211) medically necessary for individuals with ovarian cancer who have been treated with three or more prior lines of chemotherapy and are being considered for Lynparaza (olaparib). BRCA testing is considered experimental and investigational for all other indications not listed above, including screening of breast or ovarian cancers, as well as assessment of risk of other cancers such as pancreatic cancer, prostate cancer, and colon cancer because its effectiveness for these indications has not been established. Elite While there is insufficient evidence in the published medical literature to demonstrate the safety, efficacy and longterm outcomes of multi-gene next generation sequencing (NGS) panels, The Centers for Medicare & Medicaid Services (CMS) requires these panels be reviewed for medical necessity. Therefore these panels may be covered with a prior authorization for Elite members. BRCA1 and BRCA2 genetic testing for susceptibility to breast or ovarian cancer with multi-gene next generation sequencing (NGS) panels is covered as medically necessary when ALL of the following criteria are met: o Pretest and posttest genetic counseling has been performed;
- 3 - o All genes in the panel are relevant to the personal and family history for the individual being tested (panels with genes that are not relevant to the individual s personal and family history are not reasonable and necessary); o Criteria for BRCA1 and BRCA2 mutations testing listed above are met. Individual also meets criteria for at least ONE hereditary cancer syndrome for which NCCN guidelines provide clear testing criteria and management recommendations, including but not limited to HBOC, Li- Fraumeni Syndrome, Cowden Syndrome, or Lynch Syndrome. HMO, PPO, Individual Marketplace, Advantage Multigene panels (including next-generation sequencing [NGS]) for hereditary cancer susceptibility are considered experimental and investigational and therefore are non-covered. These tests include, but may not be limited to, the following: BRCAplus BRCAvantage Plus BreastNext BreastTrue High Risk Panel BREVAGen Invitae Breast Cancer High-Risk Panel myrisk Hereditary Cancer OvaNext OncoVue Breast Cancer Risk Test CODING/BILLING INFORMATION The appearance of a code in this section does not necessarily indicate coverage. Codes that are covered may have selection criteria that must be met. Payment for supplies may be included in payment for other services rendered. CPT CODES 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 (ie, 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 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 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 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 14 genes, including ATM, BRCA1, BRCA2, BRIP1, CDH1, MLH1, MSH2, MSH6, NBN, PALB2, PTEN, RAD51C, 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 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 Codes that Support Medical Necessity C25.0 Malignant neoplasm of head of pancreas C25.1 Malignant neoplasm of body of pancreas C25.2 Malignant neoplasm of tail of pancreas C25.3 Malignant neoplasm of pancreatic duct C25.4 Malignant neoplasm of endocrine pancreas C25.7 Malignant neoplasm of other parts of pancreas C25.8 Malignant neoplasm of overlapping sites of pancreas C25.9 Malignant neoplasm of pancreas, unspecified
- 4 - C48.1 Malignant neoplasm of specified parts of peritoneum C50.011 Malignant neoplasm of nipple and areola, right female breast C50.012 Malignant neoplasm of nipple and areola, left female breast C50.019 Malignant neoplasm of nipple and areola, unspecified female breast C50.021 Malignant neoplasm of nipple and areola, right male breast C50.022 Malignant neoplasm of nipple and areola, left male breast C50.029 Malignant neoplasm of nipple and areola, unspecified male breast C50.111 Malignant neoplasm of central portion of right female breast C50.112 Malignant neoplasm of central portion of left female breast C50.119 Malignant neoplasm of central portion of unspecified female breast C50.121 Malignant neoplasm of central portion of right male breast C50.122 Malignant neoplasm of central portion of left male breast C50.129 Malignant neoplasm of central portion of unspecified male breast C50.211 Malignant neoplasm of upper-inner quadrant of right female breast C50.212 Malignant neoplasm of upper-inner quadrant of left female breast C50.219 Malignant neoplasm of upper-inner quadrant of unspecified female breast C50.221 Malignant neoplasm of upper-inner quadrant of right male breast C50.222 Malignant neoplasm of upper-inner quadrant of left male breast C50.229 Malignant neoplasm of upper-inner quadrant of unspecified male breast C50.311 Malignant neoplasm of lower-inner quadrant of right female breast C50.312 Malignant neoplasm of lower-inner quadrant of left female breast C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast C50.321 Malignant neoplasm of lower-inner quadrant of right male breast C50.322 Malignant neoplasm of lower-inner quadrant of left male breast C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast C50.411 Malignant neoplasm of upper-outer quadrant of right female breast C50.412 Malignant neoplasm of upper-outer quadrant of left female breast C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast C50.421 Malignant neoplasm of upper-outer quadrant of right male breast C50.422 Malignant neoplasm of upper-outer quadrant of left male breast C50.429 Malignant neoplasm of upper-outer quadrant of unspecified male breast C50.511 Malignant neoplasm of lower-outer quadrant of right female breast C50.512 Malignant neoplasm of lower-outer quadrant of left female breast C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast C50.521 Malignant neoplasm of lower-outer quadrant of right male breast C50.522 Malignant neoplasm of lower-outer quadrant of left male breast C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast C50.611 Malignant neoplasm of axillary tail of right female breast C50.612 Malignant neoplasm of axillary tail of left female breast C50.619 Malignant neoplasm of axillary tail of unspecified female breast C50.621 Malignant neoplasm of axillary tail of right male breast C50.622 Malignant neoplasm of axillary tail of left male breast C50.629 Malignant neoplasm of axillary tail of unspecified male breast C50.811 Malignant neoplasm of overlapping sites of right female breast C50.812 Malignant neoplasm of overlapping sites of left female breast C50.819 Malignant neoplasm of overlapping sites of unspecified female breast C50.821 Malignant neoplasm of overlapping sites of right male breast C50.822 Malignant neoplasm of overlapping sites of left male breast C50.829 Malignant neoplasm of overlapping sites of unspecified male breast C50.911 Malignant neoplasm of unspecified site of right female breast C50.912 Malignant neoplasm of unspecified site of left female breast C50.919 Malignant neoplasm of unspecified site of unspecified female breast C50.921 Malignant neoplasm of unspecified site of right male breast C50.922 Malignant neoplasm of unspecified site of left male breast C50.929 Malignant neoplasm of unspecified site of unspecified male breast C56.1 Malignant neoplasm of right ovary C56.2 Malignant neoplasm of left ovary C56.9 Malignant neoplasm of unspecified ovary C57.00 Malignant neoplasm of unspecified fallopian tube C57.01 Malignant neoplasm of right fallopian tube C57.02 Malignant neoplasm of left fallopian tube C61 Malignant neoplasm of prostate
D05.11 Intraductal carcinoma in situ of right breast D05.12 Intraductal carcinoma in situ of left breast Z85.07 Personal history of malignant neoplasm of pancreas Z85.43 Personal history of malignant neoplasm of ovary Z85.46 Personal history of malignant neoplasm of prostate TAWG REVIEW DATES: 07/30/2002, 11/06/2003, 05/18/2005, 01/18/2006, 11/08/2006, 11/14/2007, 01/13/2010, 08/10/2011, 07/11/2012, 03/13/2013, 12/17/2015, 03/25/2016, 11/18/2016, 01/25/2018-5 - REVISION HISTORY EXPLANATION 03/31/12: Codes S3818-S3820, S3822, and S3823 were deleted 09/18/12: Updated 05/21/13: Codes 83891, 83898, 83904, 83909, 83912, 88386 were deleted as of 1/1/2013. Add/configuration of codes 81211, 81212, 81213, 81214, 81215, 81216, 81217. Per The United States Department of Labor Employee Benefits Security Administration, http://www.dol.gov/ebsa/healthreform/, determination - BRAC testing (81211, 81212, 81213, 81214, 81215, 81216, 81217) and genetic counseling (S0265) are within the scope of preventive care (member no cost share). Reviewed & approved per Medical Policy Steering Committee. 09/09/14: Changed title of policy from BRCA Testing for Breast and/or Ovarian Cancers to Genetic Testing for Breast and Ovarian Cancers. Code S0265 removed. Policy reviewed and updated to reflect most current clinical evidence per Medical Policy Steering Committee. 04/14/15: Added BRACAnalysis CDx (81211). Policy reviewed and updated to reflect most current clinical evidence per Medical Policy Steering Committee. 12/17/15: Added effective 1/1/16 new codes 81162, 81432, & 81433. Policy reviewed and updated to reflect most current clinical evidence per TAWG. 03/25/16: Added codes 81445, & 81455. Code 81433 is now non-covered for HMO, PPO, Individual Marketplace, & Elite. Policy reviewed and updated to reflect most current clinical evidence per TAWG. 11/18/16: Multigene panels for hereditary cancer susceptibility are non-covered. Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG). 11/23/16: Gender verbiage changes completed per Meaningful Access Section 1557 of the Affordable Care Act. 01/25/18: Multigene panels (including next-generation sequencing [NGS]) for hereditary cancer susceptibility are now covered with prior authorization for Elite per CMS guidelines. Added ICD-10 diagnosis codes per CMS guidelines. Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG). REFERENCES/RESOURCES Centers for Medicare and Medicaid Services, CMS Manual System and other CMS publications and services Ohio Department of Medicaid http://jfs.ohio.gov/ American Medical Association, Current Procedural Terminology (CPT ) and associated publications and services Centers for Medicare and Medicaid Services, Healthcare Common Procedure Coding System, HCPCS Release and Code Sets Industry Standard Review Hayes, Inc.