July 9, 2013 – The American Society of Clinical Oncology (ASCO) issued a newly updated clinical practice guideline today on pharmacological prevention interventions for premenopausal and postmenopausal women who are at increased risk for breast cancer.
Compared to the previous version of the guideline, this third update strongly recommends discussing the use of tamoxifen with premenopausal women and tamoxifen and raloxifene with postmenopausal women at increased risk. There is also a recommendation for discussing the option of exemestane, an aromatase inhibitor, as an alternative option for postmenopausal women.
“We now have a better understanding of the net health benefits of these interventions. This knowledge will help us identify those women in which the benefit is greater than the risk,” said Kala Visvanathan, MBBS, FRACP, MHS, co-chair of the guideline panel and associate professor of epidemiology and oncology at the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.
It also stresses the need for ongoing research on approaches to increase tamoxifen and raloxifene use in breast cancer prevention among women who are at higher risk of developing invasive breast cancer. Currently, only a small percentage of eligible women have the discussion of breast cancer risk reduction with their doctors and even consider these medications.
The updated guideline, Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline, was published today in the Journal of Clinical Oncology. The original guideline was published in 1999 and was previously updated in 2002 and 2009.The key recommendations of the guideline are as follows:
- Breast-specific gamma imaging (BSGI) provides high sensitivity for the detection of ductal carcinoma in situ (DCIS).
Tamoxifen (20 mg per day orally for five years) should be discussed as an option to reduce the risk of invasive, estrogen receptor (ER)-positive breast cancer in premenopausal or postmenopausal women. Tamoxifen targets the estrogen receptor in breast tissue, and is therefore only effective for prevention of ER-positive breast cancer.
- Raloxifene (60 mg per day orally for five years) should also be discussed as an option to reduce the risk of invasive, ER-positive breast cancer. It also targets the estrogen receptor in breast tissue. Its use is limited to postmenopausal women.
- Exemestane (25 mg per day orally for 5 years) should be discussed as an alternative to reduce the risk of invasive, ER-positive breast cancer in postmenopausal women. It is an aromatase inhibitor, a class of drugs that lower the amount of estrogen in postmenopausal women and are given to women with ER-positive breast cancer after surgery to lower the risk of the cancer coming back. While exemestane is approved for the treatment of breast cancer, the FDA has not yet approved its use in breast cancer prevention. This recommendation is based on encouraging data from a single clinical trial that showed up to a 70% reduction in overall and ER-positive invasive breast cancer incidence with exemestane compared to placebo over a three year period.
All three agents should be discussed (including risks and benefits) with women aged 35 years of older without a personal history of breast cancer who are at increased risk of developing invasive breast cancer, based on risk factors such as the woman’s age, race, and medical and reproductive history.
“Not every woman should use these preventive agents, but we believe women who are at increased risk for breast cancer should be given the option, because in some cases the magnitude of the risk reduction is large. For some women, these therapies can reduce the risk of breast cancer by up to 50%,” said Visvanathan.
The guideline provides new insight on the risks and benefits for tamoxifen and raloxifene use in postmenopausal women. The risk and benefit profile for both agents varies by age, race, level of breast cancer risk, and history of hysterectomy. The guideline emphasizes that women should discuss both the risks and benefits of these drugs with their doctors before deciding whether to take these drugs for prevention.
The guideline specifies that tamoxifen and raloxifene are not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization. In addition, tamoxifen is not recommended for use in women who are pregnant, may become pregnant or nursing mothers and should not be used in combination with hormone therapy.
ASCO has also developed clinical tools and resources to help doctors implement this guideline. The resources include a decision aid tool, which uses straightforward charts to explain the risks and benefits of breast cancer chemoprevention. ASCO has also developed a companion patient guide and graphic, available on ASCO’s cancer information website, www.cancer.net.
“The development of these agents marked a historic advance in reducing the risk of breast cancer,” said Scott M. Lippman, MD, co-chair of the guideline panel and Director of the University of California (UC), San Diego Moores Cancer Center, Senior Associate Dean and Associate Vice Chancellor for Cancer Research and Care, and Professor of Medicine at UC San Diego School of Medicine. “With the new guidelines, in conjunction with the decision aid tool, we continue to refine the use of these life-saving medications so that they can provide ever-greater benefit to women at higher risk of breast cancer.”
For more information: www.asco.org/guidelines/bcrr, www.cancer.net, and www.appliedradiationoncology.com