Tamoxifen for the prevention of breast cancer should be discussed with women aged 35 years or older who are at increased risk for the disease, according to an updated clinical practice guideline from the American Society of Clinical Oncology.
The use of raloxifene and exemestane should be discussed with postmenopausal women who are at increased risk for the disease, according to the update – the third since the guideline, entitled "Use of Pharmacologic Interventions for Breast Cancer Risk Reduction," was first published in 1999, and the first since 2009 (J. Clin. Onco. 2009;27:3235-58).
The new update includes stronger wording regarding discussion about the selective estrogen-receptor modulators tamoxifen and raloxifene, compared with the 2009 version, which stated that tamoxifen and raloxifene "may be offered" to women at increased risk.
"The committee felt that a stronger statement recommending the use of tamoxifen and raloxifene was needed given the weight of evidence from phase III randomized trials demonstrating a reduction in breast cancer risk for both tamoxifen and raloxifene," Update Committee cochair, Dr. Kala Visvanathan of Johns Hopkins Medical Institutions, Baltimore, and the other committee members reported (J. Clin. Oncol. 2013 July 8 [doi 10.1200/JCO.2013.49.3122]).
The guideline recommendations, which were published online on July 8 in the Journal of Clinical Oncology, and which are limited to pharmacologic interventions, specifically call for discussing with patients the options of:
• Oral tamoxifen treatment at a dose of 20 mg daily for 5 years to reduce the risk of estrogen receptor- (ER) positive invasive breast cancer in both pre- and postmenopausal women aged at least 35 years who are at increased risk of breast cancer or who have lobular carcinoma in situ (LCIS). Increased risk is defined as a 5-year projected absolute risk of 1.66% or greater according to the National Cancer Institute Breast Cancer Risk Assessment Tool or an equivalent measure. This "strong, evidence-based recommendation" is based on data from multiple randomized, controlled trials showing that the risk reduction benefit of this treatment continues for at least 10 years in these patients.
• Oral raloxifene treatment at a dose of 60 mg daily for 5 years to reduce the risk of ER-positive invasive breast cancer in postmenopausal women aged at least 35 years who are at increased risk or who have LCIS. This "strong, evidence-based recommendation" also is based on data from multiple randomized, controlled trials.
• Oral exemestane at a dose of 25 mg daily for 5 years as an alternative to tamoxifen or raloxifene to reduce the risk of ER-positive invasive breast cancer in postmenopausal women aged at least 35 years who are at increased risk of breast cancer or who have LCIS. This "moderate, evidence-based recommendation" is based on encouraging evidence from a single randomized, controlled trial of the aromatase inhibitor, which is approved for the treatment of breast cancer but not for breast cancer prevention.
Tamoxifen and raloxifene are not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack, nor are they recommended during prolonged immobilization. Tamoxifen is not recommended in women who are pregnant or who may become pregnant or in women who are nursing, and it should not be used in combination with hormone therapy. Exemestane should not be used in premenopausal women, according to the guideline.
"Discussions with patient and health care providers should include both the risks and benefits of each agent under consideration," the committee said.
The guideline update is based on a systematic review of more than 700 potential randomized controlled trials and meta-analyses published between June 2007 and June 2012. Ultimately, 19 articles on six different chemoprevention agents met the selection criteria of the committee, which was convened by the ASCO Clinical Practice Guidelines Committee. Members were experts – with special expertise in breast cancer – from clinical medicine, public health, clinical research, health services, and related areas such as biostatistics and epidemiology. A patient representative also was appointed to the committee.
In addition to the changes regarding the discussion of tamoxifen and raloxifene, the updated guideline also eliminates a recommendation from the 2009 version calling for a baseline gynecologic examination before initiation of treatment and annually thereafter, and removes mention of treatment with fenretinide, which the committee determined is "no longer relevant for breast cancer chemoprevention."
The committee also addressed ongoing challenges with respect to minimizing health disparities, which the committee said "are an important consideration in reducing breast cancer risk."
"Members of racial and ethnic minorities, in general, tend to be diagnosed with cancer at more advanced stages and have worse outcomes ... Awareness of these disparities in quality of care and access to care should be considered in the context of this clinical practice guideline. Health care providers should strive to deliver the highest level of cancer care to all patients," the guideline states.