Why Aren't We Doing More Breast Cancer Prevention?

Chemoprevention of breast cancer is an underutilized strategy for prevention of this very common and deadly disease. Newly published data proves that this is a developing clinical strategy and deserves the attention of any one who is involved in the health care of women.

While the ever present clamor for better breast cancer treatment continues in various forms, one of the most powerful tools against it-"chemoprevention"--continues to be ignored by the medical community. There is news now of another chemopreventive drug that should not be dismissed.

Chemoprevention is nothing more than the use of drugs to prevent an unwanted outcome-cancer-- much like using blood pressure medicine or cholesterol lowering drugs to prevent stoke and heart disease.

Tamoxifen and raloxifene (Evista) have been clearly proven as chemoprevention agents for women who are at increased risk of having breast cancer, risk factors being defined as any one of the following: age over 60, breast cell atypia, ductal carcinoma in situ (DCIS) or elevated risk score on the Gail model of breast cancer risk assessment which takes factors such as menstrual history and family history into consideration.

Despite proven efficacy with 50 percent and 38 percent reduction by tamoxifen and raloxifene respectively, prevention of breast cancer with such drugs has been an underutilized strategy. It is estimated that while over 15% of women are eligible for chemoprevention, only 0.2 % of women use chemopreventive medication. Reasons cited for such underutilization include concerns about toxicity and discomfort of primary care physicians in using drugs that have been thought of as oncologic treatments.

Tamoxifen is associated with an increased risk of venous thromboembolism, hot flashes and endometrial hyperplasia and neoplasia. Raloxifene has been associated with blood clots and stroke as well.

Excellent news now on another option is that the aromatase inhibitor, exemestane (Aromasyn) has demonstrated impressive efficacy and safety for preventing breast cancer in postmenopausal women at elevated risk In a recent international randomized double-blind study of 4,560 postmenopausal women, participants at moderate to high risk of breast cancer who received exemestane daily for up to 5 years experienced a 65% reduction in yearly incidence of invasive breast cancer at 3 years of follow-up, as compared with participants receiving placebo (www.nejm.org/doi/full/10.1056/NEJMoa1103507). These results are the biggest decline in risk of breast cancer observed in trials of any chemopreventive medication (www.cancer.gov/ncicancerbulletin/061411/page4).

Figure 2. Aromasin (exemestane)

Exemestane (Aromasyn) molecule

Moreover, exemestane significantly reduced risk of ductal carcinoma in situ (DCIS), a precursor lesion.

Additionally, exemestane has a more favorable side effect profile than does tamoxifen. When compared with placebo, exemestane did not result in a higher risk of treatment-related death, other types of cancer, cardiovascular events, or clinical skeletal fractures. Side effects of exemestane include arthritis and menopausal symptoms (such as hot flashes, arthralgia, fatigue, sweating, and insomnia).

Currently, three aromatase inhibitors, Aromasin (exemestane), Femara (letrozole), and Arimidex (anastrozole), are FDA-approved for treatment of certain types of breast cancer. At the present time, these aromatase inhibitors are not approved for primary prevention of breast cancer in post-menopausal women. Due to the efficacy and safety of exemestane, however, clinical practice eventually is likely to change to include use of exemestane for primary prevention in post-menopausal women.Other trials in progress are exploring effects of anastrozole in women at high risk of breast cancer and the combination of letrozole and tamoxifen in DCIS (www.cancer.gov/ncicancerbulletin/061411/page4).

Based on all the new information, personalized counseling of women is important in the use and choice of a chemopreventive agent and/or other strategy to lower the risk of breast cancer, reduce potential toxicity, and improve quality of life.