Updated guideline released on chemoprevention for breast cancer

The American Society of Clinical Oncology (ASCO) released a clinical practice guideline last week on pharmacologic interventions for reducing breast cancer risk.

The guideline updates the 2009 guideline on this topic and was developed based on a systematic review of 19 randomized, controlled trials and meta-analyses published from June 2007 through June 2012. Six drugs were considered: the selective estrogen-receptor modulators tamoxifen, raloxifene, arzoxifene and lasofoxifene and the aromatase inhibitors exemestane and anastrozole.

An update committee involving experts in clinical medicine, public health, clinical research, health services and related areas, plus a patient representative, reviewed the evidence and drafted the recommendations, which were then peer reviewed and reviewed and approved by the ASCO Clinical Practice Guidelines Committee. The guideline addresses only chemoprevention and does not consider survival or lifestyle interventions. It was published online July 8 by the Journal of Clinical Oncology.

The guideline recommendations include the following:

• In women at least 35 years of age who are at increased risk for breast cancer or have lobular carcinoma in situ, oral tamoxifen (20 mg/d for five years) should be discussed as an option to reduce the risk of estrogen receptor-positive disease. Tamoxifen is not recommended in women with a history of deep venous thrombosis, pulmonary embolism, stroke or transient ischemic attack. It is also not recommended in women undergoing prolonged immobilization; in women who are pregnant, may be become pregnant or are nursing; or in women taking hormone therapy.
• In postmenopausal women who are at increased risk for breast cancer or have lobular carcinoma in situ, oral raloxifene (60 mg/d for five years) should be discussed as an option to reduce risk for estrogen receptor-positive disease. Raloxifene is not recommended in premenopausal women; in women with a history of deep venous thrombosis, pulmonary embolism, stroke or transient ischemic attack; or in women undergoing prolonged immobilization.
• Oral exemestane (25 mg/d for five years) should also be discussed as an alternative to tamoxifen or raloxifene to reduce risk of estrogen receptor-positive disease in postmenopausal women who are at increased risk for breast cancer, who have lobular carcinoma in situ, or who have atypical hyperplasia. It is not recommended for breast cancer risk reduction in premenopausal women. The guideline noted that exemestane is currently FDA-approved only for adjuvant treatment of early breast cancer and treatment of advanced breast cancer.

Increased risk was defined as a five-year projected absolute risk of 1.66% or greater (based on the National Cancer Institute Breast Cancer Risk Assessment Tool or an equivalent measure) or a diagnosis of lobular carcinoma in situ. The guideline does not recommend using other selective estrogen-receptor modulators or aromatase inhibitors to lower breast cancer risk outside a clinical trial setting. Of note, fenretinide is no longer included in the 2013 guideline update because the update committee considered it no longer relevant for breast cancer chemoprevention.

Clinicians are encouraged to discuss the option of chemoprevention with women at increased breast cancer risk, the guideline said, including the specific risks and benefits associated with each prospective agent.