Health First Pharmacogenetic Testing Form

Medical Policy Subject: Prophylactic Cancer Surgery - Risk Policy Number: MP-0228 Effective Date: January 2024 Revised: N/A Document Page Length: 11 Applies To: Management All Lines Note Medicare will also follow: • Breast Reconstruction Following Mastectomy NCD140.2 • Ovarian Cancer - Tumor Antigen by Immunoassay - CA 125 NCD 190.28 and • First Coast BRCA1 and BRCA2 Genetic Testing LCD (L36499) • First Coast Genetic Testing for Lynch Syndrome LCD 34912 Medical Policy Statement: Prophylactic mastectomy, prophylactic hysterectomy and/or prophylactic bilateral oophorectomy may be considered medically necessary when the clinical criteria described in this policy are met. Definitions: Genetic Counseling: Genetic counseling is the process of helping individuals understand and adapt to the medical, psychological, and familial indications of genetic contributions to disease. Genetic counseling services include predisposition evaluation and genetic diagnosis. Genetic counseling may be necessary, both pre-and post-genetic test, to interpret family and medical histories to assess the chance of disease occurrence and recurrence, educate regarding inheritance, testing, management prevention and resources, and counsel to promote informed choices and adaptation to risk or condition. Lynch Syndrome - A term sometimes used to refer to families who have HNPCC with colorectal cancer only, while Lynch II refers to families who have other cancers, such as endometrial or ovarian, in addition to colorectal cancer. Identifying patients with Lynch syndrome is clinically important because these patients have up to 80 percent lifetime risk of colorectal cancer and up to 60 percent lifetime risk of endometrial cancer. Prophylactic Mastectomy - A surgical procedure (usually simple or total mastectomy) that removes all breast tissue that would be otherwise subject to breast carcinoma. Prophylactic Oophorectomy - Removal of the ovaries before development of cancerous cells. Prophylactic Hysterectomy - Removal of the uterus before development of cancerous cells. Salpingo - Fallopian tubes Description: A risk factor is anything that increases chances of getting a disease, such as cancer. Some risk factors for cancer are things that cannot be changed, inheriting certain gene changes. These make risk of cancer higher. About 5% to 10% of breast cancer cases are thought to be hereditary, meaning that they result directly from gene changes (mutations) passed on from a parent. • BRCA1 and BRCA2: The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 gene. In normal cells, these genes help make proteins that repair damaged DNA. Mutated versions of these genes can lead to abnormal cell growth, which can lead to cancer. A mutated copy of either gene from a parent, causes higher risk of breast cancer. On average, a woman with a BRCA1 or BRCA2 gene mutation has up to a 7 in 10 chance of getting breast cancer by age 80. This risk is also affected by how many other family members have had breast cancer. (It goes up if more family members are affected.) Women with one of these mutations are more likely to be diagnosed with breast cancer at a younger age, as well as to have cancer in both breasts. Women with one of these gene changes also have a higher risk of developing ovarian cancer and some other cancers. (Men who inherit one of these gene changes also have a higher risk of breast and some other cancers.) In the United States, BRCA mutations are more common in Jewish people of Ashkenazi (Eastern Europe) origin than in other racial and ethnic groups, but anyone can have them. • Other genes: Other gene mutations can also lead to inherited breast cancers. These gene mutations are much less common, and most of them do not increase the risk of breast cancer as much as the BRCA genes. o ATM: The ATM gene normally helps repair damaged DNA (or helps kill the cell if the damaged can't be fixed). Inheriting 2 abnormal copies of this gene causes the disease ataxia-telangiectasia. Inheriting one abnormal copy of this gene has been linked to a high rate of breast cancer in some families. o PALB2: The PALB2 gene makes a protein that interacts with the protein made by the BRCA2 gene. Mutations in this gene can lead to a higher risk of breast cancer. o TP53: The TP53 gene helps stop the growth of cells with damaged DNA. Inherited mutations of this gene cause Li-Fraumeni syndrome. People with this syndrome have an increased risk of breast cancer, as well as some other cancers such as leukemia, brain tumors, and sarcomas (cancers of bones or connective tissue). This mutation is a rare cause of breast cancer. o CHEK2: The CHEK2 gene is another gene that normally helps with DNA repair. A CHEK2 mutation increases breast cancer risk. o PTEN: The PTEN gene normally helps regulate cell growth. Inherited mutations in this gene can cause Cowden syndrome, a rare disorder that puts people at higher risk for both cancer and benign (non-cancer) tumors in the breasts, as well as growths in the digestive tract, thyroid, uterus, and ovaries. o CDH1: Inherited mutations in this gene cause hereditary diffuse gastric cancer, a syndrome in which people develop a rare type of stomach cancer. Women with mutations in this gene also have an increased risk of invasive lobular breast cancer. o STK11: Defects in this gene can lead to Peutz-Jeghers syndrome. People affected with this disorder have pigmented spots on their lips and in their mouths, polyps (abnormal growths) in the urinary and digestive tracts, and a higher risk of many types of cancer, including breast cancer. Inherited mutations in several other genes have also been linked to breast cancer, but these account for only a small number of cases. o Genetic counseling and testing: General population testing is not recommended or required. However, genetic testing is done for those at high risk to look for inherited mutations in the BRCA1 and BRCA2 genes (or less commonly in genes such as PTEN, TP53, or others mentioned above). This might be an option for some women who have been diagnosed with breast cancer, as well as for certain women with factors that put them at higher risk for breast cancer, such as a strong family history. Genetic testing for those with high risk factors allows for decision making to manage risks. Genetic counseling is recommended to assist the member in making informed decisions in response to genetic testing. Clinical Criteria: (Indications/Limitations) I. Prophylactic mastectomies are considered medically necessary for patients at increased risk of developing breast carcinoma who have one or more of the following: A. Women diagnosed with breast cancer at 45 years of age or younger; B. Women who are at increased risk for specific mutation(s) due to ethnic background (for instance: Ashkenazi Jewish descent) and who have one or more relatives with breast cancer or epithelial ovarian cancer at any age; C. Women who carry a germline genetic mutation in theCDH1, TP53, PTEN or PALB2 genes; D. Women who possess BRCA1 or BRCA2 mutations confirmed by molecular susceptibility testing for breast and/or epithelial ovarian cancer; E. Women who received radiation treatment to the chest between ages of 10 and 30 years, such as for Hodgkin disease; F. Women with a first- or second-degree male relative with breast cancer (Note: Prophylactic removal of contralateral breast tissue is considered medically necessary in men with breast cancer); G. Women with multiple primary or bilateral breast cancers in a first- or second- degree blood relative;. H. Women with multiple primary or bilateral breast cancers; I. Women with one or more cases of epithelial ovarian cancer and one or more first- or second-degree blood relatives on the same side of the family with breast cancer; J. Women with three or more affected first- or second-degree blood relatives on the same side of the family, irrespective of age at diagnosis; K. Atypical hyperplasia of lobular or ductal origin confirmed on biopsy; L. Fibronodular, dense breasts which are mammographically and/or clinically difficult to evaluate and patient presents with at least one of the above clinical presentations. II. Prophylactic bilateral oophorectomy or salpingo-oophorectomy are considered medically necessary in selected women with risk factors for epithelial ovarian carcinoma -including nulliparity, low parity, infertility, early menarche, late menopause, and late first pregnancy - if they meet any of the following criteria: A. Women who are beyond child-bearing age (40 years of age or older) who have been diagnosed with an hereditary epithelial ovarian cancer syndrome based on a family pedigree constructed by a genetic counselor or physician competent in determining the presence of an autosomal dominant inheritance pattern; B. Women who have two first-degree relatives (e.g., mother, sister, daughter) with a history of epithelial ovarian cancer; C. Women with a personal history of breast cancer and at least one first-degree relative (e.g., mother, sister, daughter) with history of epithelial ovarian cancer; D. Women with BRCA1 or BRCA2 germline mutations confirmed by molecular susceptibility testing; E. Women who carry a germline genetic mutation in the BRIP1, RAD51C, RAD51D, MLH1 or MSH2 genes; F. Women with one first-degree relative (e.g., mother, sister, daughter) and one or more second-degree relatives (e.g., maternal or paternal aunt, grandmother, niece) with epithelial ovarian cancer. III. Prophylactic Hysterectomy with Prophylactic Oophorectomy are considered medically necessary for patients who have one or more of the following A. The medical literature suggests that a prophylactic hysterectomy should be performed in conjunction with oophorectomy in women from families with Lynch syndrome. B. For women who have been diagnosed with HNPCC (Hereditary Non- polyposis Colorectal Cancer) or are found to be carriers of HNPCC- associated mutations. C. For women from families with breast-ovarian cancer syndrome, site-specific ovarian cancer syndrome, or a family history of epithelial ovarian cancer who choose to have prophylactic oophorectomy, the choice to have prophylactic hysterectomy in conjunction with oophorectomy depends on the women's attitudes regarding hormone replacement and the potential morbidity from the hysterectomy, either abdominally or vaginally. IV. Multigene Panel Testing for Moderate to High Penetrance Breast and/or Epithelial Ovarian Cancer Susceptibility Genes A. HFHP considers once per lifetime genetic testing medically necessary for persons who meet one or more National Comprehensive Cancer Network (NCCN) testing criteria for high-penetrance breast cancer susceptibility genes germline multigene panel testing for moderate to high-penetrance breast and/or epithelial ovarian cancer susceptibility genes (must include BRCA1, BRCA2, CDH1, MLH1,MSH2, MSH6, PALB2, PTEN, STK11, TP53) and full duplication and deletion analysis (i.e., detection of large genomic rearrangements) (must include BRCA1, BRCA2, MLH1, MSH2,and STK11). Limitations: I. Experimental and Investigational: A. HFHP considers prophylactic mastectomy experimental and investigational for all other indications than those listed in the criteria above (e.g., diabetic mastopathy, fibrocystic breast disease, pseudo-angiomatous stromal hyperplasia (PASH)) because the effectiveness for indications other than the ones listed above has not been established. B. Elective salpingectomy for ovarian cancer prevention in low hereditary risk women because of insufficient evidence of its effectiveness. C. Prophylactic mastectomy for men with BRCA mutations or family history of breast cancer because there is no clinical data on the clinical value of this approach and there are no guidelines on this situation. II. Breast and Ovarian Cancer Susceptibility Gene Testing limitations / not considered medically necessary: A. Not considered medically necessary for individuals less than18 years of age. B. Asymptomatic individuals with a family history that meets criteria for testing, who do not have a causative variant already identified, should not rely solely on BRCA1 or BRCA2 gene testing as the current standard of care includes moderate-high penetrance gene analysis to guide future screening and management recommendations. C. Breast and ovarian cancer gene susceptibility testing of members if testing is performed primarily for the medical management of other family members that are not covered by HFHP.