Breast Cancer: Genetic Risk Assessment and BRCA Mutation Testing

Evidence Statement Benefit Plan Language Other Information and Resources Author(s)

References


Updated 10/3/11

Evidence Statement

Clinical Preventive Service Recommendations

U.S. Preventive Services Task Force Recommendation
The U.S. Preventive Services Task Force (USPSTF) recommends that women whose family history is associated with an increased risk of deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing.1

Evidence Rating: B (Recommended/At Least Fair Evidence)
The USPSTF found fair evidence that women with certain specific family history patterns (increased-risk family history) have an increased risk for developing breast or ovarian cancer associated with BRCA1 or BRCA2 mutations. The USPSTF determined that these women would benefit from genetic counseling that allows informed decision making about testing and further prophylactic treatment. This counseling should be done by suitably trained healthcare providers. There is fair evidence that prophylactic surgery significantly decreases breast and ovarian cancer incidence in women who test positive for deleterious BRCA1 or BRCA2 mutations, although there is insufficient evidence to determine other health-outcome benefits from intensive screening or preventive medication in such women.1

NOTE:
The U.S. Preventive Services Task Force (USPSTF) recommends against routine referral for genetic counseling or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with an increased risk for deleterious mutations in breast cancer susceptibility. The USPSTF concluded that the potential harms of routine referral for genetic counseling or BRCA testing in these women outweigh the benefits.1

Back to top

The Value of Prevention

Economic Burden of Condition/Disease
The direct medical care costs for breast cancer treatment were estimated to exceed $6 billion in 1996.8 The total economic burden of breast cancer would be much higher if breast cancer related mortality and morbidity costs were included in this figure. In 2004, for example, the overall cost of cancer (including direct and indirect cots) was estimated to be almost $190 billion9, and breast cancer could account for up to one-quarter of this total.10 A small proportion of the economic burden of breast cancer is attributable to genetically-related breast cancers.

The risk of breast cancer increases with age.7 Population aging in the coming decades is expected to increase the number of breast cancer cases and the economic burden of the disease.
Workplace Burden of Condition/Disease
Women aged 40 to 64 years accounted for 61% of in situ cases, 54% of invasive breast cancer cases, and 40% of breast cancer deaths in 2005.2 The breast cancer medical care costs, productivity losses, and mortality costs among working women in this group is substantial.
Economic Benefit of Counseling, Testing and Preventive Treatment
The recognition of BRCA mutations through testing allows for early intervention and treatment. This is important because women who receive early treatment generally have better outcomes. For example, in one research model, a 30-year-old BRCA1 and 2 positive woman could prolong her life by about 1 year by having bilateral oophorectomy, 3.4 years by having bilateral mastectomy, and 4.3 years by having both procedures instead of surveillance alone.11
Estimated Cost of Counseling, Testing and Preventive Treatment
In 2004, the private-sector cost of BRCA mutation testing averaged $53 per test; approximately 95% of all paid claims fell within the range of $12 to $201 per test.12 The cost of genetic counseling averaged $39 per session; approximately 95% of all paid claims fell within the range of $0 to $129 per session.12 The cost of a preventive mastectomy or oophorectomy varies by location and facility type.
Cost-Effectiveness and/or Cost-Benefit Analysis of Counseling, Testing and Preventive Treatment
One study, using modeling techniques, concluded that BRCA1 and BRCA2 testing is cost-effective only if women who screen positive proceed with prophylactic surgery.13 The model further suggested that, per life-year saved, combined surgery cost $20,717, mastectomy cost $29,970, and oophorectomy cost $72,780 (all figures in year 1995 dollars).13 Another study, which also used modeling techniques, concluded that for women who are positive for a BRCA1 or BRCA2 genetic mutation, prophylactic surgery at a young age significantly improves survival and is cost-effective in comparison to other interventions.14

Back to top

Condition / Disease Specific Information

Epidemiology of Condition/Disease
Breast cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death among women in the United States.2 In 2005, 211,000 women are expected to be diagnosed with breast cancer and 40,000 women are expected to die as a result of breast cancer.2
Condition/Disease Risk Factors
Risk factors for breast cancer (reported by the USPSTF) include:3
  • A family history of breast cancer (especially a mother or sister with breast cancer)
  • Atypical hyperplasia
  • Having a first child after the age of 30
  • Increasing age
Risk factors reported by other organizations include:4-6
  • Early age at menarche
  • Late age at menopause
  • Overweight/obesity
  • Physical inactivity
  • Hormone replacement therapy
  • Exposure to radiation
Another risk factor for breast cancer is the presence of genetic markers for the BRCA1 or BRCA2 genes.6 However, only a small proportion of breast cancer cases are attributable to genetic susceptibility. Approximately 2% of adult women in the United States have a family history indicating they are at increased risk of a deleterious mutation in the BRCA1 or BRCA2 gene, and about 1 in 10 women with these histories (2 to 3 per 1,000 adult US women) actually have a mutation.7 Among women with a deleterious BRCA1 or BRCA2 mutation, 35% to 84% may develop breast cancer by age 70.7

Back to top

Preventive Intervention Information

Purpose of Counseling, Testing and Preventive Treatment
The purpose of family history assessment, counseling, and BRCA mutation-testing is to identify women with certain specific family history patterns that are associated with an increased risk for deleterious mutations in the BRCA1 or BRCA2 gene and an increased risk of breast or ovarian cancer. With the assistance of genetic counseling, women at risk can make an informed decision on testing and treatment options.
Benefits and Risks of Counseling, Testing and Preventive Treatment
The USPSTF determined that women with certain specific family history patterns benefit from genetic counseling that allows informed decision making about testing and preventive treatment (e.g., removal of the breasts and/or ovaries).1 The USPSTF found fair evidence that prophylactic surgery significantly decreases the incidence of breast and ovarian cancer among women with a BRCA mutation. Thus, the potential benefits of referral and discussion of testing and prophylactic treatment for these women may be substantial. The inherent risk associated with preventive treatment and surgery, such as patient anxiety and medical errors, may be substantial for some individuals.

The USPSTF concluded that for women whose family history is not associated with an increased risk of deleterious mutations, the harms of routine referral for counseling and testing outweigh the benefits.1
Initiation of Counseling, Testing and Preventive Treatment
Patients identified as high-risk through a clinician risk assessment should be referred for genetic counseling and, if appropriate, follow-up genetic mutation testing. The initiation, cessation, and frequency of counseling is left to the discretion of the clinician. A onetime BRCA test should be administered to at-risk patients who request testing. Preventive treatment including mastectomy and/or ophorectomy should be conducted, as medically necessary, at the discretion of the clinician.

Note: The USPSTF realizes that clinical decisions about patients involve more complex considerations that the evidence alone; clinicians should always understand the evidence but individualize decision making to the specific patient and situation.
Intervention Process: Counseling, Testing and Preventive Treatment
The clinician should assess the patient's family history of breast cancer to determine the likelihood that the patient has a deleterious BRCA mutation.1 If the assessment is positive, the woman should be referred for genetic counseling to help determine if she wishes to have genetic testing. Women may require further counseling after test results are received. A positive test for a deleterious mutation may result in a decision to have the surgical removal of her breasts and/or ovaries. Coverage should include clinician time to evaluate family history for possible referral to a genetic counselor, counseling on the harms and benefits of genetic testing by a qualified practitioner, and preventive treatment (e.g., complete mastectomy with or without reconstructive surgery, ophorectomy).
Treatment Information
Health benefits should include provisions for diagnostic and treatment services.

Back to top

Strength of Evidence for the Clinical Preventive Service Breast Cancer (Screening)

The level of evidence supporting the recommendations contained in this section is described below.
Evidence-Based Research:
U.S. Preventive Services Task Force (USPSTF)
Strength of Evidence: B (Recommended/At Least Fair Evidence)
  • The USPSTF found fair evidence that women with certain specific family history patterns (increased risk family history) have an increased risk for developing breast or ovarian cancer associated with BRCA1 or BRCA2 mutations.1
Note: The USPSTF recommended against routine referral for genetic counseling or gene testing for women whose family history is not associated with an increased risk of deleterious mutations as the USPSTF concluded that the potential harms of routine referral for genetic counseling or BRCA testing in these women outweigh the benefits.1

Back to top

Summary Plan Description

Summary Plan Description Language: Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Counseling)

Covered Counseling
Beneficiaries determined to be at high risk for breast cancer based on the results of a clinician's risk assessment are eligible for genetic counseling.
Initiation, Cessation, and Interval
Counseling is provided as medically indicated, and should be conducted at least once before and after genetic testing.

Summary Plan Description Language: Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Testing)

Covered Testing
Beneficiaries determined to be at high risk for breast cancer based on the results of a clinician's risk assessment are eligible for BRCA mutation testing.
Initiation, Cessation, and Interval
BRCA mutation testing is covered once per lifetime.

Summary Plan Description Language: Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Preventive Treatment)

Covered Preventive Treatment
Beneficiaries determined to be at high risk for breast cancer based on the results of a clinician's risk assessment or the results of BRCA mutation testing are eligible for preventive treatment, which may include any of the following:
  • Surgical removal of the breast(s) with or without reconstructive surgery
  • Surgical removal of the ovaries
Treatment coverage includes counseling-based office visits for treatment education, decision-making, and monitoring.
Initiation, Cessation, and Interval
Preventive treatment is provided, as medically indicated.

Back to top

CPT Codes


Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Counseling)
99401 Preventive medicine counseling/risk factor reduction, 15 minutes
99402 Preventive medicine counseling/risk factor reduction, 30 minutes
99403 Preventive medicine counseling/risk factor reduction, 45 minutes
99404 Preventive medicine counseling/risk factor reduction, 60 minutes
Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Testing)
83890 Molecular diagnostics; molecular isolation or extraction
83891 Molecular diagnostics; isolation or extraction of highly purified nucleic acid
83892 Molecular diagnostics; enzymatic digestion
83893 Molecular diagnostics; dot/slot blot production
83894 Molecular diagnostics; separation by gel electrophoresis
83896 Molecular diagnostics; nucleic acid probe, each
83897 Molecular diagnostics; nucleic acid transfer
83898 Molecular diagnostics; amplification of patient nucleic acid, each nucleic acid sequence
83900 Molecular diagnostics; amplification of patient nucleic acid, multiplex, first two nucleic acid sequences
83901 Molecular diagnostics; amplification of patient nucleic acid, multiplex, each additional nucleic acid
83902 Molecular diagnostics; reverse transcription
83903 Molecular diagnostics; mutation scanning by physical properties, single segment, each
83904 Molecular diagnostics; mutation identification by sequencing, single segment, each segment
83905 Molecular diagnostics; mutation identification by allele specific transcription, single segment, each segment
83906 Molecular diagnostics; mutation identification by allele specific translation, single segment, each segment
83907 Molecular diagnostics; lysis of cells prior to nucleic acid extraction
83908 Molecular diagnostics; signal amplification of patient nucleic acid, each nucleic acid sequence
83909 Molecular diagnostics; separation and identification by high resolution technique
83912 Molecular diagnostics; interpretation and report
88271 Molecular cytogenetics; DNA probe, each
88272 Molecular cytogenetics; chromosomal in situ hybridization, analyze 3 - 5 cells
S3818* Complete gene sequence analysis; BRCA1 gene
S3819* Complete gene sequence analysis; BRCA2 gene
S3820* Complete BRCA1 and BRCA2 gene sequence analysis for susceptibility to breast and ovarian cancer
S3822* Single mutation analysis (in individual with a known BRCA1 or BRCA2 mutation in the family) for susceptibility to breast and ovarian cancer
S3823* Three-mutation BRCA1 and BRCA2 analysis for susceptibility to breast and ovarian cancer in Ashkenazi individuals
Breast Cancer Genetic Risk Assessment and BRCA Mutation Testing (Preventive Treatment)
19301 Mastectomy, partial
19302 Mastectomy, partial; with axillary lymphadenectomy
19303 Mastectomy, simple, complete
19304 Mastectomy, subcutaneous
19305 Mastectomy, radical, including pectoral muscles, axillary lymph nodes
19306 Mastectomy, radical, including pectoral muscles, axillary and internal mammary lymph nodes
19307 Mastectomy, modified radical, including axillary lymph nodes, with or without pectoralis minor muscle, but excluding pectoralis major muscle
19340 Immediate insertion of breast prosthesis following mastectomy
19342 Delayed insertion of breast prosthesis following mastectomy
19357 Breast reconstruction, immediate or delayed, with tissue expander, including subsequent expansion
19361 Breast reconstruction with latissimus dorsi flap, with or without prosthetic implant
19364 Breast reconstruction with free flap
19366 Breast reconstruction with other technique
19367 Breast reconstruction with transverse rectus abdmoninis myocutaneous flap, single pedicle, including closure of donor site
19368 Breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM), single pedicle, including closure of donor site; with microvascular anastomosis
19369 Breast reconstruction with transverse rectus abdmoninis myocutaneous flap, double pedicle, including closure of donor site
58661 Laparoscopy, surgical; with removal of adnexal structures
58720 Salpingo-oophorectomy, complete or partial, unilateral or bilateral
58940 Oophorectomy, partial or total, unilateral or bilateral
99401 Preventive medicine counseling/risk factor reduction, 15 minutes
99402 Preventive medicine counseling/risk factor reduction, 30 minutes
99403 Preventive medicine counseling/risk factor reduction, 45 minutes
99404 Preventive medicine counseling/risk factor reduction, 60 minutes

Back to top

Other Information and Resources

Business Group Resource(s)

CDC Resource

Back to top

Author(s)

Campbell KP, Coates RJ, Lanza A, Chattopadhyay S. Breast cancer evidence-statement: screening, counseling, testing, preventive medication, and preventive treatment. In: Campbell KP, Lanza A, Dixon R, Chattopadhyay S, Molinari N, Finch RA, editors. A Purchaser's Guide to Clinical Preventive Services: Moving Science into Coverage. Washington, DC: National Business Group on Health; 2006. Updated 2011.

Back to top

References

  1. U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility. Summary of Recommendation. Agency for Healthcare Research and Quality; September 2005. Available at: http://www.ahrq.gov/clinic/uspstf/uspsbrgen.htm. Accessed May 20, 2009.
  2. American Cancer Society. Breast cancer facts & figures 2005-2006. Atlanta, GA: American Cancer Society, Inc.; 2005.
  3. Berg AO, Atkins D. Screening for breast cancer: recommendation and rationale. Ann Intern Med. 2002;137(5 Part 1):344-6.
  4. International Agency for Research on Cancer. Weight control and physical activity. IARC Handbooks of cancer prevention. Vol. 6. Lyon: IARC Press; 2002.
  5. Curry SJ, Byers T, Hewitt M, editors. Fulfilling the potential of cancer prevention and Early detection. Washington, DC: National Academies Press; 2003.
  6. National Cancer Institute. Breast cancer PDQ treatment. General information about breast cancer. Available at: http://www.nci.nih.gov/cancertopics/pdq/treatment/breast/patient/. Accessed May 21, 2009.
  7. Nelson HD, Hoyt Huffman L, Fu R, Harris EL. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2005;143:362-7.
  8. Brown ML, Lipscomb J, Snyder C. The burden of illness of cancer: economic cost and quality of life. Annu Rev Public Health. 2001;22:91-113.
  9. American Cancer Society. Cancer facts & figures 2005. Atlanta, GA: American Cancer Society; 2005.
  10. Radice D, Redaelli A. Breast cancer management: quality of life and cost considerations. Pharmacoeconomics. 2003;21:383-96.
  11. Grann VR, Jacobson JS, Whang W, Hershman D, Heitjan DF, Antman KH, Neugut AI. Prevention with tamoxifen or other hormones versus prophylactic surgery in BRCA1/2-positive women: a decision analysis. Cancer J Sci Am. 2000;6(1):13-20.
  12. Thomson Reuters. 2004 MarketScan® Commercial Commercial Claims and Encounters Database. 2005.
  13. Grann VR, Whang W, Jacobson JS, Heitjan DF, Antman KH, Neugut AI. Benefits and cost of screening Ashkenazi Jewish women for BRCA1 and BRCA2. J Clin Oncol. 1999;17(2)494-500.
  14. U.S. Preventive Services Task Force. Screening for breast cancer. AHRQ Publication No. APPIP02-0016. Rockville (MD): Agency for Health Care Research and Quality; 2002.