By Ann Steagall
Accountable Care Act Ruling
On January 10, 2014 it was announced that the Department of Health & Human Services (HHS) issued guidance to “clarify that under the Affordable Care Act, most health insurance companies and employer plans must cover tamoxifen and raloxifene – like other recommended preventative services – without co-pays or other out of pocket expenses for women at increased risk for breast canceri.”
This applies to women whose private insurance policies were written after the law was signed in 2010, as well as women on Medicaid or Medicareii.
This article summarizes the NCCN Guidelines Version 1.2013 concerning Breast Cancer Risk Reductioniii.
The NCCN uses the Modified Gail Model of relative risk assessment in determining which women are considered to be at higher risk of developing breast canceriii. The Gail model is based on:
- Age, age at first menarche and first live birth
- The number of first degree relatives who have been diagnosed with invasive breast cancer
- The number of breast biopsies a patient has undergone
- Any atypical hyperplasia demonstrated on any of the previous biopsies (hyperplasia is increased cell production in a normal tissue or organ)
In addition BRCA1/2 mutational carriers are also considered at higher risk for developing breast cancer, however the use of risk reducing agents in this population has not been fully substantiated with trial data.
Of note, women who are 35 years of age or older and have Gail model 5 year relative risk of breast cancer > 1.7% or a history of lobular carcinoma in situ (LCIS) are considered candidates for risk reduction.
Risk Reduction Measures
Risk reduction surgery is a primary option for women who are known carriers of BRCA1/2 mutations. The lifetime risk of developing invasive breast cancer for this population is reported to be 56-84%. Retrospective analysis has demonstrated that bilateral risk reduction mastectomies (RRM) reduced the risk of developing breast cancer more than 90% of the time.
Risk reduction surgery for BRCA1/2 carriers can be done with or without immediate reconstruction but should include complete removal of all breast tissue. Women with normal breast screening prior to surgery do not need axillary node sampling. After surgery women who are carriers of the BRCA1/2 mutations should be monitored according to the NCCN guidelines for genetic and familial risks.
Additionally, carriers of BRCA1/2 are reported to have a lifetime risk of 36-46% of developing ovarian cancer. BRCA1/2 carriers who underwent risk reduction surgery for ovarian cancer had an approximate risk reduction of 80%.
Carriers of BRCA1/2 mutations are also at higher risk for ovarian cancer although not as high as breast cancer. In the BRCA 1 mutational group the overall lifetime risk is reported to be 36-46% while in the BRCA2 carriers it is a bit lower at 10-27%. With the lack of reliable early screening and the poor prognosis of advanced ovarian carcinoma performing bilateral salpingo-oophrectomies (RRSO) in these women after childbearing has been completed is an option. The mean age at diagnosis for women who are BRCA1/2 carriers is approximately 51 years of age. A meta-analysis of 10 studies of BRCA1/2 carriers who underwent risk reduction surgery for ovarian cancer had an approximate risk reduction of 80%. There remained a small (1-4.3%) risk of developing primary peritoneal carcinoma as reported by these studies. Undergoing RRSO also decreased the risk of these women developing breast cancer by approximately 50%. Women who elect to undergo risk reduction surgical procedures should continue to routine health maintenance and screenings.
Prevention with hormonal therapy
Multiple prevention studies have been conducted worldwide. The first of these studies was the NSABP BCPT also known as P-1. This study looked specifically at women over the age of 35 who had an increased risk of breast cancer. The women were randomized to receive Tamoxifen or placebo. The overall reduction in risk after long term follow up in these women has been reported to be 43%. A subset analysis of women with BRCA 1/2 mutations was reported to have decreased the risk of breast cancer by 62% in women who carried BRCA2 but BRCA1 carriers did not show a risk reduction. In 1998 based on the results of P-1 the FDA granted approval to Tamoxifen as a breast cancer risk reduction agent.
Subsequent studies to P-1 include the Royal Marsden Hospital study, The Italian Tamoxifen Prevention Study and the International Breast Cancer Prevention study. More than 17,000 women were studied across all trials. The only study which did not show a risk reduction with the use of Tamoxifen was the Italian study. Reasons for this are unclear but it is thought to be affected by concurrent use of hormonal therapy as well as possibly lower risk women being included.
Three studies were completed using the agent raloxifene instead of Tamoxifen. These studies had complicated designs and also looked at various endpoints regarding heart disease, osteoporosis and bone fracture with breast cancer development not always the primary endpoint. However when one looks at the cumulative results of these studies it is clear that raloxifene decreased the risk of invasive breast cancer significantly especially ER+ breast cancers. Study results as high as 76% risk reduction were reported.
The NSABP STAR trial or P-2 was a head to head comparison of Tamoxifen vs raloxifene. The trial was initiated in 1999 and the first results were reported in 2006. This single study enrolled almost 20,000 women who were 35 years of age or older, had a calculated increased risk of developing breast cancer of at least 1.7% in 5 years or had a history of LCIS. At 4 years both drugs appeared to be equal but at 8 years raloxifen was about 76% as effective as Tamoxifen suggesting that Tamoxifen has a better long term effect of reducing invasive breast cancer development. There was a lower incidence of serious side effects in the women who took raloxifen which makes it a viable option for women who have increased risk for thromboembolic events or who cannot tolerate Tamoxifen.
Tamoxifen: The NCCN strongly recommends Tamoxifen as the superior option for breast cancer risk reduction.
- The recommended dose for women 35 years old or older with a life expectancy of at least 10 years and a 5 year relative risk of breast cancer that is equal to or greater than 1.7 % or has a history of LCIS is 20mg orally every day for 5 years. The usage carries a NCCN category 1 recommendation which means that the NCCN breast committee unanimously agrees that the data are superior and warrant this indication.
Raloxifene: In addition the NCCN also gives a category 1 recommendation to women at high risk for the development of breast cancer, and are post-menopausal and have a comorbid conditions that warrant not using Tamoxifen to use raloxifene at a dose of 60mg orally every day for 5 years.
Exemestane: At least 2 trials using aromatase inhibitor (exemestane) have shown a relative risk reduction of developing invasive breast cancer when compared to placebo. One trial has reported the benefit to be upwards of 65% when compared to placebo.
- Based on the data from these trials, exemestane has also been added as an option for use as a breast cancer risk reduction agent however it does not have an FDA indication for this use. While there are no randomized data that compare the use of exemestane to Tamoxifen or raloxifen the NCCN has given its use a category 1 recommendation when at risk women with co-morbid conditions such a osteoporosis and possible increased risk of toxicity to Tamoxifen have been identified. The recommended dose of exemestane if used is 25mg per day orally for at least 3 years. There are ongoing trials at this time to evaluate the use of long term aromatase inhibitors as breast cancer risk reduction agents.
|Tamoxifen – S0187|
|NDCs||00591-2473-30 – 20mg tabs, 30 ct00591-2473-19 – 20mg tabs, 90ct63739-0269-10 – 10mg tabs, 10 ct
|Raloxifene (no J or S code)|
|NDCs||00002-4165-07 – 60mg, 2000 ct00002-4165-30 – 60mg, 30 ct00002-4165-02 – 60mg, 100 ct
|Exemestane – S0156 (25mg)|
|NDCs||00054-0080-13 – 25mg, 30 ct59762-2858-01 – 25mg, 30ct09-7663-04 – 25mg, 30ct
i Sebelius K, Schultz DW. More than 2.8 million reasons for hope [blog]. HHS.gov/HealthCare Web site.http://www.hhs.gov/healthcare/facts/blog/2014/01/reasons-for-hope.html. Published January 9, 2014. Accessed January 10, 2014
ii Kennedy K. Preventive breast cancer drugs now available at no cost. USA Today. http://www.usatoday.com/story/news/nation/2014/01/09/breast-cancer-prevention-drugs-available-with-no-out-of-pocket-costs/4391879/. Published January 9, 2014. Accessed January 10, 2014.
iii NCCN Guidelines Version 1.2013, “Breast Cancer Risk Reduction,” 4/19/2013
iv U.S. Department of Health and Human Services, www.guideline.gov/content.asapx?id=38601&search=brca1%2f2