Abstract
The U.S. Preventive Services Task Force recently released a draft recommendation suggesting that clinicians offer risk-reducing medications, including tamoxifen, raloxifene, and aromatase inhibitors, to women who have an increased risk of developing breast cancer and a low risk of side effects.
The U.S. Preventive Services Task Force (USPSTF) recently released, in draft format, updated recommendations for breast cancer prevention—namely that clinicians offer risk-reducing medications, including aromatase inhibitors (AI), to women with an increased risk of the disease and a low risk of side effects (available at www.uspreventiveservicestaskforce.org).
The statement makes a small but notable shift from the agency's 2013 recommendation by adding the AIs anastrozole and exemestane to the list of acceptable risk-reducing medications, which already includes the selective estrogen receptor modulators tamoxifen and raloxifene (Ann Intern Med 2016;164:279–96).
Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine at Queen Mary University in London, UK, considers the USPSTF's addition of AIs a positive development. He notes that this is the first time a U.S. government agency has recommended the drugs, which, unlike tamoxifen and raloxifene, are not FDA approved for preventive use. The USPSTF guidelines now align with those of the American Society of Clinical Oncology and the National Comprehensive Cancer Network, which already recommend AIs to postmenopausal women at increased risk.
As in the past, the USPSTF statement suggests that clinicians formally assess risk with the NCI Breast Cancer Risk Assessment tool or other algorithm, or consider risk factors such as family history and abnormal cells on a prior breast biopsy without using a formal tool.
Cuzick sees risk assessment as a major hurdle for prescribing preventive therapies. “Risk is a complicated business, based on more than just single factors, and increasingly people are using risk models to determine what the risk is, rather than just individual factors,” he says. The Tyrer-Cuzick Model, which Cuzick helped develop, combines individual factors and family history with information on breast density and genetic risk factors.
Additionally, the USPSTF continues to stress that the potential benefits of taking the medications must be balanced against possible side effects, which can include blood clots, hot flashes, and increased risk of endometrial cancer, among others. “We'd like drugs that have fewer side effects, but still, the balance looks quite favorable for most women at high risk,” Cuzick says.
Ball-and-stick model of anastrozole, C17H19N5.
Researchers are studying how to reduce side effects. For example, in a phase III trial presented at the 2018 San Antonio Breast Cancer Symposium in Texas, women with a noninvasive breast abnormality given a low dose (5 mg) of daily tamoxifen for 3 years reduced their risk of developing invasive breast cancer by 52% with no significant side effects; a typical regimen of 20 mg daily for 5 years seems to provide a comparable benefit with more side effects. An ongoing phase III trial is investigating the effectiveness of a tamoxifen gel applied directly to the breasts to prevent the disease.
Cuzick hopes that the USPSTF statement will boost prevention efforts. “There's no doubt that preventive therapy is underused in breast cancer,” he says. “It's a personal choice as to what a woman wants to do, but I think it's a good option, and it's certainly worth giving it a try.” –Catherine Caruso
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