It is estimated that more than 100,000 American women are diagnosed with estrogen receptor (ER)–positive, postmenopausal breast cancer each year, accounting for about half of all women with breast cancer in the United States. “ER–positive breast cancer is the single most common breast cancer diagnosis in the country,” says Harold J. Burstein, MD, PhD. “One of the most important treatments for women with postmenopausal breast cancer is anti-estrogen therapy.”

Filling in Knowledge Gaps

Tamoxifen and aromatase inhibitors (AIs) are treatments that can be used as adjuvant therapy after initial surgery, chemotherapy, and/or radiation in an effort to prevent breast cancer recurrences. In 2010, the American Society of Clinical Oncology (ASCO) issued a guideline update on the use of adjuvant hormone therapy for women with hormone receptor-positive breast cancer, revising previous guidelines from 2004. For the most recent update, ASCO’s Endocrine Therapy for Breast Cancer Update Committee conducted a systematic review of the available medical literature to develop the recommendations. “We reviewed the wealth of research that has emerged in the past several years on anti-estrogen drugs,” explains Dr. Burstein, who co-chaired the Update Committee. “Our missions were to fill in gaps in our understanding of how best to use these newer treatments and to gain better clarity on the trade-offs and side effects of these therapies.”

ASCO’s updated guideline reviews recent research on both AIs and tamoxifen. Tamoxifen is a selective ER modulator, which blocks estrogen’s ability to reach the ER and stimulate residual cancer growth. AIs work differently in that they deplete the production of estrogen in postmenopausal women. “Tamoxifen and AIs work by different mechanisms and have different safety profiles,” Dr. Burstein notes. “It’s important that clinicians discuss the side effects of these drugs with patients. Giving patients a better understanding of these therapies will empower patients to choose treatments that are most appropriate for them. These discussions are essential to maximizing compliance to therapy.”

Key Recommendations

According to the guidelines, use of an AI alone or in combination with tamoxifen therapy reduces the recurrence risk and improves disease-free survival when compared with tamoxifen monotherapy. The Update Committee recommended that all postmenopausal women with hormone receptor-positive breast cancer use an AI either alone or before or after tamoxifen to reduce recurrence risk. Women are also recommended to use AIs for extended periods, after 5 years of tamoxifen therapy, to lower their recurrence risk.

Several new recommendations have emerged since the last update in 2004 (Table 1). “A key recommendation is that most postmenopausal women should consider taking an AI at some point during their course of therapy, either as initial adjuvant therapy or after 2 to 3 years of tamoxifen,” explains Dr. Burstein. Women can take up to 5 years of an AI therapy, and that can be started even after 5 years of tamoxifen therapy. In that setting, a woman could receive up to 10 years of hormone treatment to reduce their risk of recurrence. The guideline also notes that tamoxifen should be given to all pre- and perimenopausal women. “AIs are only effective in postmenopausal women,” adds Dr. Burstein. “Women who are pre- or perimenopausal at the time of their diagnosis should be treated with 5 years of tamoxifen.”

The Update Committee found no clinically important differences in effectiveness among AIs. The guideline also notes that, overall, most women have relatively mild side effects on either AIs or tamoxifen. When compared with tamoxifen, AIs may reduce blood clot and uterine cancer risks, but may increase the risk of osteoporosis and fractures. In addition, no evidence was found to validate the use of specific biomarkers to determine which treatment strategies would benefit patients the most.

Use Available Resources

The ASCO guidelines made several recommendations for additional needed research (Table 2). In the meantime, Dr. Burstein recommends reviewing the current update to improve the management of women with hormone receptor-positive breast cancer. The guidelines on the use of adjuvant hormone therapy for these patients were published in the August 2010Journal of Clinical Oncology and are available online at www.asco.org/guidelines/endocrinebreast. ASCO has also developed a patient guide (www.cancer.net) to assist clinicians further. Dr. Burstein adds that “utilizing these resources can help physicians ensure that patients are treated appropriately and educated so that they can make the best possible decisions. In turn, the hope is that they will enhance outcomes for the long term.”

References

Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer. J Clin Oncol. 2010;6:243-246.Available at: http://jco.ascopubs.org/cgi/reprint/JCO.2009.26.3756v1.

Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: Status report 2004. J Clin Oncol. 2005;23:619-629.

Eisen A, Trudeau M, Shelley W, et al. Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: A systematic review. Cancer Treat Rev. 2008;34:157-174.

 Hind D, Ward S, De Nigris E, et al. Hormonal therapies for early breast cancer: systematic review and economic evaluation. Health Technol Assess. 2007;11:iii-iv, ix-xi, 1-134.