A new study confirms that taking tamoxifen for five years better protects most breast cancer patients from a recurrence of the disease than a shorter regimen.

Although the drug has been used for 25 years to treat women with breast cancer, there has been some dispute over just how long to continue treatment. Researchers in Italy compared a two-year regimen with a five-year regimen in women with early-stage breast cancer. They reported their results in the Journal of Clinical Oncology (Vol. 21, No. 12: 2276-2281).

The researchers studied 1,901 women between the ages of 50 and 70 who had undergone surgery for early stage invasive breast cancer (some had also had radiation therapy). All began taking tamoxifen soon after their initial treatment to try to prevent recurrence. After two years, about half the women stopped taking tamoxifen; the rest continued taking the drug for three more years, for a total of five years.

The researchers followed the women for more than four years after the first group stopped tamoxifen treatment. Overall, they found little difference between the two groups when they looked at how many women had died and how many women had a recurrence of their disease.

But when they examined only women with estrogen-receptor positive tumors, they found a significant difference. More than 28% of these women who took tamoxifen for just two years had a recurrence of their cancer (166 women), compared to 23.5% among the five-year tamoxifen group (131 women). Tamoxifen works by blocking the effect of estrogen, which promotes the growth of ER-positive tumors.

Women in the five-year group experienced more blood clots than women in the two-year group, but the researchers determined that the cancer protection they received from the tamoxifen outweighed this risk. The researchers say one way to address the problem of blood clots is to give women at high risk for clots newer drugs like anastrozole, which are effective but have lower incidence of this side effect.

The debate over how long to continue tamoxifen use has centered on the fact that it has potentially harmful side effects. Previous research has shown it can increase the risk of blood clots in the legs and lungs, as well as cancers of the uterus. Because of this, doctors have looked to see if they could lower this risk while maintaining the same level of protection against breast cancer recurrence.

“Previous studies have shown the five-year mark to be about optimal, and this study confirms it,” says Rick Alteri, MD, a medical editor for the American Cancer Society.

The fact that the results were better in women with estrogen-receptor positive tumors was not a surprise, he adds, and is in line with current practice in the United States. “Most doctors have breast cancer specimens tested for estrogen receptor status, and only prescribe tamoxifen if it is positive. This study also validates the wisdom of this approach.”