Guideline adds aromatase inhibitor for breast cancer prevention

The new update to the 2009 American Society of Clinical Oncology (ASCO) guideline on the pharmacologic interventions for breast cancer risk reduction now lists aromatase inhibitor exemestane (Aromasin, Pfizer) as an option for postmenopausal women for primary risk reduction who are at an increased risk of developing invasive breast cancer. 

The updated guideline, Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline, was published in the Journal of Clinical Oncology. The original guideline was published in 1999 and was previously updated in 2002 and 2009.

Previous guidelines had suggested discussing prophylactic use of raloxifene (Evista, Lilly) in postmenopausal women at risk for breast cancer and tamoxifen in both pre- and postmenopausal women at risk. Earlier guidelines stressed that use of aromatase inhibitors as prevention was not recommended outside of clinical trials.

The key recommendations of the guideline are:

· Tamoxifen (20 mg per day orally for 5 years) should be discussed as an option to reduce the risk of invasive, estrogen receptor (ER)-positive breast cancer in premenopausal or postmenopausal women. Tamoxifen targets the estrogen receptor in breast tissue, and is therefore only effective for prevention of ER-positive breast cancer.  

· Raloxifene (60 mg per day orally for 5 years) should also be discussed as an option to reduce the risk of invasive, ER-positive breast cancer.  It also targets the estrogen receptor in breast tissue. Its use is limited to postmenopausal women.

· Exemestane (25 mg per day orally for 5 years) should be discussed as an alternative to reduce the risk of invasive, ER-positive breast cancer in postmenopausal women. It is an aromatase inhibitor, a class of drugs that lower the amount of estrogen in postmenopausal women and are given to women with ER-positive breast cancer after surgery to lower the risk of the cancer coming back. While exemestane is approved for the treatment of breast cancer, the FDA has not yet approved its use in breast cancer prevention. This recommendation is based on encouraging data from a single clinical trial that showed up to a 70% reduction in overall and ER-positive invasive breast cancer incidence with exemestane compared to placebo over a 3-year period.

· All 3 agents should be discussed (including risks and benefits) with women aged 35 years of older without a personal history of breast cancer who are at increased risk of developing invasive breast cancer, based on risk factors such as the woman’s age, race, and medical and reproductive history.

Exemestane is not approved by FDA for breast cancer prevention, however the ASCO guideline panel made the new recommendation based on the results of MAP.3, a randomized placebo-controlled double blind trial. After a median follow-up of 3 years, exemestane showed a statistically significant 73% risk reduction in the overall risk of invasive breast cancer.  Based on this data, the new recommendation is that exemestane should be discussed as an alternative to tamoxifen and/or raloxifene to reduce the risk of invasive breast cancer in appropriate patients.

There were no statistically significant differences in serious adverse events, but exemestane was observed to have a statistically significant difference regarding endocrine-related adverse events, but minimal differences in quality of life outcomes were observed. Exemestane was also found to worsen age-related bone loss, despite supplementation with calcium and vitamin D. 

“Exemestane is not for every patient, but is a reasonable option for primary prevention of breast cancer in post-menopausal females with an increased risk of invasive breast cancer,” said Cara A. Harshberger, PharmD, BCOP, University of Wyoming, School of Pharmacy, clinical assistant professor of pharmacy practice, clinical pharmacy specialist, oncology, University of Colorado Health.

“The benefit of exemestane in these populations, outweighs the risk of bone loss and vasomotor symptoms, and should be added to the formulary for primary prevention in postmenopausal females at high risk for invasive breast cancer,” Dr Harshberger told Formulary. “Bone loss is a well-known adverse effect from aromatase inhibitors, and the addition of bisphosphonates has been shown to increase bone mineral density while on these medications.  I would suspect that many patients may be initiated on bisphosphonates up front if indicated, based on bone mineral density testing.” 

According to Dr Harshberger, another aromatase inhibitor, anastrozole, is currently being studied for the primary prevention of invasive breast cancer in postmenopausal women.  “The results of the IBIS-II trial will provide more information on the use of anastrozole in this setting in the near future,” she said.