Preventive Therapy for Breast Cancer
With more than 226,000 new cases and 39,000 deaths annually, breast cancer is the most common cancer in American women.1 Risk factors for breast cancer that confer the most risk are those that cannot be modified—for example, family history, age, and age at menarche.2
Tamoxifen was among the first pharmacologic interventions found to reduce a woman's risk for developing breast cancer.2,3 This strategy, originally called “chemoprevention,” is now known as “preventive therapy” to avoid possibly negative associations with chemotherapy.4 Therapies used for cancer prevention must meet different standards than those used for treatment. The usefulness of these therapies is therefore strongly influenced by individual patients' risk profiles and personal preferences.2
An estimated 10 million US women are eligible for preventive therapy, but despite established efficacy, few take advantage of it.5,6Approximately 4% of those at increased risk for breast cancer and 0.08% of American women aged 40 to 79 years use preventive therapy.7 Thus, the challenges for clinicians are identifying women at risk, choosing the appropriate therapy, and communicating the benefits of preventive therapy to increase its acceptance and use among women.
For purposes of preventive therapy, a woman's breast cancer risk is estimated using the National Cancer Institute (NCI) risk assessment (“Gail”) model. This tool predicts absolute 5-year breast cancer risk for women 35 years of age or older based on individual risk factors including age, family history, and race/ethnicity; it does not account for the presence of BRCA mutations, history of lobular carcinoma in situ (LCIS), or radiation exposure. Median risk (based on an average 60-year-old woman) is approximately 1.7%, which in clinical trials has been used to identify those at higher risk.6,8-10 However, it cannot specify risk for known subtypes of breast cancer with clinical implications, specifically estrogen receptor (ER) -positive versus ER-negative disease.2
Preventive Therapy: Current Options
There is a well-established role for selective hormone receptor modulators (SERMs) and exemestane in reducing risk for ER-positive breast cancer based on the results of multiple, well-designed prevention trials.2,4,11
The SERMs tamoxifen and raloxifene block estrogen receptors to prevent estrogen binding and activation without decreasing circulating estrogen levels.6Across four primary prevention trials, tamoxifen reduced the risk of invasive ER-positive breast cancer by 43%; importantly, the benefit in reduced rates of breast cancer and mortality continued for at least 5 years after completion of tamoxifen treatment.4 The first-choice for preventive therapy for high-risk premenopausal women is a5 mg/day dose, as no increased risk in endometrial cancer has been observed in 10 or more years of follow-up.4,12