BREAST CANCER (Counseling and Preventive Medication)

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

References


Updated 12/12/11

Evidence Statement

Clinical Preventive Service Recommendations

U.S. Preventive Services Task Force Recommendation
The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians discuss preventive medication with women at high risk for breast cancer and at low risk for adverse effects of preventive medication use. Clinicians should inform patients of the potential benefits and harms of preventive medication.1

Evidence Rating: B (Recommended/At Least Fair Evidence)
The USPSTF found fair evidence that treatment with tamoxifen can significantly reduce the risk of invasive estrogen-receptor-positive breast cancer in women at high risk for breast cancer and that the likelihood of benefit increases as the risk for breast cancer increases. Although raloxifene is not now FDA-approved for this use, the USPSTF found consistent, but less abundant, evidence for its benefit as well. The USPSTF found good evidence that estrogen antagonists (e.g., tamoxifen) increase the risk for thromboembolic events (for example, stroke, pulmonary embolism, and deep vein thrombosis) and symptomatic side effects (for example, hot flashes) and that tamoxifen increases the risk of endometrial cancer.1

The USPSTF concluded that the balance of benefits and harms may be favorable for some high-risk women but will depend on breast cancer risk, risk from potential harms and individual patient preferences.1

Note: The U.S. Preventive Services Task Force (USPSTF) recommends against routine use of tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer.1



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 2007 (the most recent year numbers are available) over 200,000 women in the United States were diagnosed with breast cancer and more than 40,000 women in the United States died from 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



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 costs) 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 Preventive Medication
The use of preventive medication in carefully-selected, high-risk women can reduce their risk of breast cancer or delay the onset of breast and ovarian cancers. It is estimated that for every 100 women treated with tamoxifen for 5 years, 1.665 expected cancers are delayed or prevented. If breast cancer death is fully prevented by this strategy, then the use of preventive medication (compared to no intervention) would cost $8,479 per year of life gained.11

Estimated Cost of Preventive Medication
The average wholesale price (AWP) of a 1-month supply of tamoxifen citrate is between $58.38 (generic) and $128.62 (brand – Nolvadex®).12

Estimated Cost of Treatment
The cost of breast cancer treatment depends on the stage of disease at diagnosis and the procedures or treatments selected. Treatment costs have been reported to range from $21,287 to $45,220 per patient. However, terminal care costs for Medicare patients were reported to be as high as $63,455 (all figures in year 2002 dollars).7

Cost-Effectiveness and/or Cost-Benefit Analysis of Preventive Medication
Tamoxifen is cost-effective for women aged 40 to 50 years who are at significant risk for breast cancer.13 Tamoxifen costs $46,619 per life-year saved for women who begin taking the medication at age 35. For women over the age of 50, the intervention costs more than $50,000 per life-year saved.14



Preventive Intervention Information

Preventive Intervention: Purpose of Counseling and Preventive Medication
The purpose of preventive medication counseling is to educate women at high risk of breast cancer on the benefits and risks associated with tamoxifen.

Benefits and Risks of Counseling and Preventive Medication
Among women at high risk for breast cancer, an estrogen antagonist (i.e., tamoxifen) has been found to reduce the incidence of invasive breast cancer by approximately one-half.1,15

Estrogen antagonists increased survival by 1.6 years (range 1.0 to 2.1 years) and 2.2 years (range 1.3 to 2.8 years), respectively. Research shows that preventive medication yields more quality-adjusted life years than does prophylactic surgery, even when treatment is delayed to age 40 or 50 years.16

Estrogen antagonists are associated with an increased risk of venous thromboembolic disease (deep vein thrombosis and pulmonary embolism); tamoxifen is also associated with an increased risk of endometrial cancer.1,15

The balance between benefits and harms varies among subgroups of women, depending on age, predicted risk of breast cancer, and hysterectomy status. In general, the balance of benefits and harms of preventive medication is more favorable for women in their 40s who are at increased risk for breast cancer and have no predisposition to thromboembolic events or women in their 50s who are at increased risk for breast cancer, have no predisposition to thromboembolic events, and do not have a uterus. Women are at lower risk for adverse effects from preventive medication if they are younger; have no predisposition to thromboembolic events such as stroke, pulmonary embolism, or deep venous thrombosis; or do not have a uterus.

The USPSTF concluded that routine use of estrogen antagonists for the primary prevention of breast cancer in women at low or average risk for breast cancer would cause more harm than benefit.1

Initiation and Cessation of Counseling and Preventive Medication
The initiation and cessation of preventive medication therapy with an estrogen antagonist is left to the discretion of the clinician (in discussion with the patient). In general, preventive medication is more favorable for women in their 40s who are at increased risk for breast cancer and have no predisposition to thromboembolic events or women in their 50s who are at increased risk for breast cancer, have no predisposition to thromboembolic events, and do not have a uterus.1 Women younger than 40 years of age have a lower risk for breast cancer, and thus will not experience as large an absolute benefit from beast cancer preventive medication as older women.1 Women 60 years of age and older, who have the highest risk for breast cancer also have the highest risk for complications from preventive medication/chemoprevention with a less favorable balance of benefits and harms.1 The standard course of preventive medication with tamoxifen in clinical trials is 5 years.29

Intervention Process: Preventive Medication
Clinicians should assess a patient's risk for breast cancer and the risk for adverse preventive medication effects when identifying women who may be candidates for preventive medication therapy. Clinicians can assess a patient's risk of developing breast cancer within the next 5 years using risk-factor information from the National Cancer Institute Breast Cancer Risk Tool (the "Gail Index"). Clinicians should discuss the results of the risk assessment, inform the patient of the risks associated with breast cancer, and counsel about the benefits and risks associated with the use of preventive treatment. Clinicians should counsel on the harms and benefits of preventive medication use and prescribe an FDA-approved preventive medication to eligible women who choose to use preventive medication. Coverage should include clinician time to monitor the potential harms/adverse effects associated with preventive medication use and the cost of the preventive medication approved for use by the FDA.

Treatment Information
Health benefits should include provisions for diagnostic and treatment services.



Strength of Evidence for the Clinical Preventive Service Breast Cancer (Counseling and Preventive Medication)

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 recommends that clinicians discuss preventive medication with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Clinicians should inform patients of the potential benefits and harms of chemoprevention.1
Note: The USPSTF recommends against routine use of tamoxifen for the primary prevention of breast cancer in women at low or average risk for breast cancer.1 Recommended Guidance:
American Society of Clinical Oncology (ASCO)
Strength of Evidence: Expert Opinion
  • The American Society of Clinical Oncology suggests that women with sufficient risk, based on the Gail Index, be offered tamoxifen to reduce their risk of breast cancer.3


Summary Plan Description

Summary Plan Description Language: Breast Cancer (Counseling on Preventive Medication and Preventive Treatment)

Covered Counseling
Beneficiaries determined to be at high-risk for breast cancer based on the results of the clinician's risk assessment or the results of BRCA mutation testing are eligible for counseling on the use of preventive medication or preventive treatments.

Initiation, Cessation, and Interval
Counseling is provided as medically indicated.

Summary Plan Description Language: Breast Cancer (Preventive Medication)

Covered Preventive Medications
Beneficiaries determined to be at high risk for breast cancer based on the results of a clinician's risk assessment are eligible for preventive medication. Coverage is provided for all FDA-approved breast cancer preventive medications (e.g., tamoxifen).

Initiation, Cessation, and Interval
Coverage is provided for 5 years. Preventive treatment may be extended, if continued treatment is determined to be medically necessary.

CPT Codes

Breast Cancer Preventive Medication and Preventive Treatment (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 (Preventive Medication)
S0187* Tamoxifen citrate, oral 10 mg



Other Information and Resources

Business Group Resource(s)

CDC Resource



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.



References

1 U.S. Preventive Services Task Force. Chemoprevention of breast cancer: Recommendations and rationale. Rockville, MD: Agency for Healthcare Research and Quality; July 2002.
2 U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999-2007 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2010. http://www.cdc.gov/uscs.
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 Smith TJ, Hillner BE. Tamoxifen should be cost-effective in reducing breast cancer risk in high-risk women. (Comment). J Clin Oncol. 2000;18(2):284-6.
12 Fleming T. 2006 Redbook: Pharmacy's fundamental reference. Thomson PDR; Rev Ed edition. May 2006.
13 Cykert S, Phifer N, Hansen C. Tamoxifen for breast cancer prevention: a framework for clinical decisions. (Comment) Am J Obstet Gynecol. 2004; 104(3):431-2.
14 Grann VR, Sundararajan V, Jacobson JS, Whang W, Heitjan DF, Antman KH, Neugut AI. Decision analysis of tamoxifen for the prevention of invasive breast cancer. Cancer Journal. 2000;6(3):169-78.
15 Kinsinger LA, Harris R, Lewis C, Woddell M. Chemoprevention of breast cancer systematic evidence review No.8. Rockville, MD: Agency for Healthcare Research and Quality; July 2002. Available at http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat3.chapter.2527. Accessed May 21, 2009.
16 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.