The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on the use of pharmacologic interventions for breast cancer risk reduction. The guidelines, published in the July 1, 2009 Journal of Clinical Oncology, incorporate data from relevant randomized trials that have been published in the past several years. “These guidelines are intended to assist physicians and patients in clinical decision making,” says Kala Visvanathan, MD, MHS, lead author of the guidelines. “While maintaining a healthy lifestyle is important in terms of reducing risk, the updated guidelines focus on breast cancer risk reduction agents. The recommendations are beneficial for clinicians seeing women who have not previously had breast cancer but are at increased risk for the disease.” Dr. Visvanathan adds that women should be given the option to consider risk reduction agents, and physicians should be prepared to discuss the risks and benefits of the agents for each individual woman.
Two Significant Updates
The two primary modifications to the guidelines address the use of tamoxifen and raloxifene as options to reduce the risk of estrogen receptor (ER)-positive invasive breast cancer. Postmenopausal women who are at risk for breast cancer may benefit from taking either raloxifene or tamoxifen risk reduction agents, according to the guidelines. Previously, ASCO only recommended tamoxifen (Table 1).
The addition of raloxifene (60 mg/d) for 5 years as a risk reduction option of ER-positive invasive breast cancer for postmenopausal women was based on the STAR (Study of Tamoxifen and Raloxifene) trial, a randomized study that compared tamoxifen to raloxifene in postmenopausal women. “Findings from the STAR trial demonstrated that raloxifene was as effective as tamoxifen in reducing invasive breast cancer risk in postmenopausal women,” Dr. Visvanathan says. “It was also associated with a lower risk of thromboembolic disease, benign uterine complaints, and cataracts when compared with tamoxifen.”
In addition, the ASCO panel included updated information on tamoxifen based on recently published long-term follow-up data. “Findings from these trials better establish the benefits of tamoxifen and the patterns of potential adverse side effects,” says Dr. Visvanathan. “In particular, long-term data have found that vascular and vasomotor side effects (eg, hot flashes, sweats, and menstrual irregularities), which are important concerns for patients and physicians, have been shown to decrease after active treatment. This information now enables physicians and patients to make well-informed decisions when considering risk reduction treatment options.”
Risk Assessment & Communication
The Breast Cancer Risk Assessment Tool of the National Cancer Institute is the most commonly used model to assess a woman’s risk of developing invasive breast cancer. It has been validated for use in most women aged 35 or older and provides an individual’s 5-year and lifetime risk estimates for developing the disease on the basis of several questions. “This tool should be used to assess a woman’s risk in the short and long term,” notes Dr. Visvanathan. “A woman’s breast cancer risk can increase with age as well as with future abnormal biopsies and changes in family history. Evaluating breast cancer risk should be ongoing over a woman’s lifetime.”
Before a risk reduction strategy is chosen, the risks and benefits of both tamoxifen and raloxifene—including risks of noninvasive breast cancer, adverse events, and impact on quality of life—should be discussed with postmenopausal women (Table 2). “A disclosure of risks and benefits should be initiated,” says Dr. Visvanathan. “Furthermore, the potential impact of each agent on the incidence of both noninvasive and invasive breast cancers should be discussed. It’s also helpful to provide information on ER-positive and ER-negative breast cancers because the efficacy of different agents varies for these two types of tumors.”
Looking Into the Future
According to Dr. Visvanathan, there remains a need for further research of risk reduction agents, such as aromatase inhibitors and retinoids, which are currently being evaluated in early-phase trials. “Retinoids appear to hold promise to prevent ER-negative breast cancer,” she says. “Raloxifene and tamoxifen don’t significantly impact ER-negative cancers. ER-positive cancers are more common overall, especially in older women, but ER-negative cancers can be more aggressive and more common in younger women. There is a great need to develop agents that also prevent ER-negative cancers.”
In addition, ongoing randomized clinical trials are being performed to determine if aromatase inhibitors will further reduce the incidence of ER-positive invasive breast cancer. Other agents such as tibolone (a synthetic hormone) and lasofoxifene (a selective estrogen receptor modulator) are also being evaluated, but these therapies are not yet FDA approved.
Kala Visvanathan, MD, MHS, has indicated to Physician’s Weekly that she has or has had no financial interests to report.
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