The American Society of Clinical Oncology (ASCO) today issued a guideline update on the use of adjuvant hormone therapy for women with hormone receptor-positive breast cancer. The Update Committee, convened by ASCO, reviewed evidence compiled through a systematic review of the medical research literature to develop the recommendations. The guideline will be published online today in the Journal of Clinical Oncology (JCO).

The guideline ? which updates ASCO?s previous recommendations on adjuvant hormonal therapy for breast cancer ? reviews recent research on both aromatase inhibitors (AIs) and tamoxifen, recommending that all post-menopausal women with hormone receptor-positive breast cancer use an AI either alone or before or after tamoxifen to reduce the risk of recurrence. Women may also use AIs for extended periods, after five years of tamoxifen therapy, to lower their recurrence risk.

More than 100,000 women each year in the United States are diagnosed with estrogen receptor ?positive, postmenopausal breast cancer ? about half of all American women with breast cancer ? making it the single most common breast cancer diagnosis of in this country. The anti-estrogen drug tamoxifen, and more recently AIs, are used as adjuvant, or additional, therapy after initial surgery, chemotherapy and/or radiation to attempt to prevent breast cancer recurrences.

?One of the most important treatments for women with postmenopausal breast cancer is anti-estrogen therapy,? said breast cancer specialist Harold J. Burstein, MD, PhD, co-chair of ASCO?s Endocrine Therapy for Breast Cancer Update Committee and Associate Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute in Boston. “Our panel carefully reviewed the explosion of research that has emerged in the past 5 years on anti-estrogen drugs, and filled in gaps in our understanding of how best to use these newer treatments, and what the trade-offs and side effects of therapy would be.”

Tamoxifen and aromatase inhibitors work by different mechanisms and have different safety profiles. “The Panel emphasized the importance of discussing side effects of these drugs with patients, to help patients better understand and choose between the treatments and do all we can to maximize compliance with these important therapies,” said Jennifer Griggs, MD, MPH, co-chair of ASCO?s Endocrine Therapy for Breast Cancer Update Committee and Associate Professor in the University of Michigan Department of Internal Medicine, Division of Hematology/Oncology.

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The Committee examined recent evidence from 12 prospective, randomized trials that compared tamoxifen and one of the three AIs as part of adjuvant breast cancer therapy. The studies showed that the use of an AI either alone or combined with tamoxifen therapy, compared to tamoxifen alone reduced the risk of recurrence and improved disease-free survival. Specifically, the use of an AI reduced the risk of in-breast recurrence and cancer in the opposite breast, as well as reducing the risk of distant metastases, compared to tamoxifen alone.

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The Committee made several new recommendations, updating the previous guideline- from 2004- including:
– Most postmenopausal women should consider taking an AI at some point during the course of therapy, either as the initial adjuvant therapy or after two to three years of tamoxifen. Women can take up to five years of an AI therapy. AI therapy can also begin after five years of tamoxifen therapy. In that setting, a woman could receive up to 10 years of hormone treatment to reduce the risk of recurrence.
– Tamoxifen should be given to all pre- and peri-menopausal women; AIs are only effective in post-menopausal women. The guideline recommends that women who are pre- or peri-menopausal at the time of diagnosis be treated with five years of tamoxifen.
– The Committee found no clinically important differences in effectiveness among the three commercially available AIs (anastrozole, letrozole, and exemestane). This is the first update where data is available for each in all three clinical settings (primary, sequential or extended adjuvant).
– The guideline also includes a review characterizing side effect profiles of tamoxifen and AIs, compiled from the 12 trials considered. While the two drug classes work differently, overall, most women have relatively mild side effects on either drug. (Tamoxifen is a selective estrogen receptor modulator, blocking estrogen?s ability to reach the estrogen receptor and stimulate residual cancer growth. AIs, in contrast, deplete the production of estrogen in post-menopausal women.). When compared with tamoxifen, aromatase inhibitors may reduce the chance of blood clots and uterine cancer and may increase the risk of osteoporosis and fractures.

The guideline Update Committee found no evidence that validated the use of a specific biomarker to determine which treatment strategy would be better for patients.
The guideline made several recommendations for additional needed research, including:
– Tumor marker or pathology studies aimed at finding if there are certain types of hormone-receptor positive breast cancers that respond better to one treatment approach or drug compared to the other.
– Ongoing studies comparing five years of AI therapy versus longer durations and studies comparing the optimal time to switch from tamoxifen to an AI.
– Definitive analyses of the role of drug metabolism and pharmacogenetics as predictors of benefit or treatment options.
– Strategies to improve adherence to therapy.

ASCO published its initial clinical practice guideline on the use of adjuvant hormone therapy for women with estrogen-positive breast cancer in 2002, and followed with two updates in 2003 and 2004.

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