Posted online March 10, 2008, on www.jco.org.

A multicenter phase III clinical trial has reported that the drug letrozole cuts the risk of breast cancer recurrence and spread by more than 60 percent in postmenopausal women with early-stage disease who completed five years of tamoxifen therapy one to seven years earlier. The study was published in the Journal of Clinical Oncology (JCO).

While tamoxifen has been a very important and effective part of breast cancer treatment, more than half of all recurrences and two-thirds of breast cancer deaths occur after five years of tamoxifen therapy. Yet additional tamoxifen beyond five years of treatment has not proven effective.

Like tamoxifen, letrozole is a tablet taken once daily. It belongs to a group of drugs called aromatase inhibitors, which work by blocking an enzyme the body needs to make the estrogen that most breast cancers need to grow. Women with early-stage breast cancer whose tumors are fueled by estrogen typically receive five years of tamoxifen after surgery to reduce their risk of recurrence.

A number of studies in the past several years have found that aromatase inhibitors are effective in postmenopausal women for reducing recurrence rates after surgery; after just two or three years of tamoxifen; or very soon after completing five years of tamoxifen treatment.

The study of letrozole was led by the National Cancer Institute of Canada Clinical Trials Group. They found that letrozole reduced the risk of recurrence by 63 percent and reduced the risk of cancer spread by 61 percent, even when started one to seven years after completion of tamoxifen treatment. There was also an 82 percent reduction in the risk of developing a new cancer in the opposite breast among the women taking letrozole.

Researchers also found that the reduced risk of breast cancer recurrence persisted among all age groups, including women over 70, who are sometimes given less aggressive therapy due to concerns over side effects and the extent of benefit. There were no differences in the side effects of letrozole or quality of life between the different age groups.

Most patients did not experience significant side effects from letrozole, though women who received letrozole experienced more bone fractures and osteoporosis than those on placebo (5.2 versus 3.1 percent).

In another study published in the same issue of JCO, researchers with the National Surgical Adjuvant Breast and Bowel Project showed that after four years, postmenopausal women with early-stage breast cancer who took another aromatase inhibitor called exemestane (initiated shortly after completing tamoxifen therapy) had a 56 percent reduced risk of recurrence, compared with women who took a sugar pill. Exemestane was well tolerated by most of the women.

What Does This Mean for Patients?

Postmenopausal women who have already finished five years of tamoxifen—including those who completed therapy several years ago—may want to speak with their doctors about starting a new course of treatment with letrozole to further reduce their risk of breast cancer recurrence.

These data also indicate that older women derive the same benefit from letrozole as younger patients, and they should be considered for extended therapy after tamoxifen treatment is completed.

All women, especially those who have gone through menopause, should have their bone health assessed regularly. Because aromatase inhibitors have been associated with a slightly increased risk of fractures and osteoporosis, doctors generally recommend that women have their bone health assessed before starting aromatase inhibitor therapy.