5-YEAR LIMIT URGED FOR TAMOXIFEN TREATMENT.

Byline: Charles Bankhead Medical Tribune News Service

Five years of treatment with the anti-estrogen drug tamoxifen significantly reduces the risk of cancer recurrence and death in women with a history of breast cancer, according to results of two different studies.

However, continuing tamoxifen beyond five years offers no additional benefits and may even be harmful, one of the studies indicated.

More cancer recurrences and deaths have occurred among women who continued therapy for 10 years, Dr. Bernard Fisher, a distinguished service professor at the University of Pittsburgh, reported at the American Society of Clinical Oncology meeting.

``Five years of tamoxifen should be the standard duration of therapy for patients who are given the drug to prevent breast cancer recurrence after surgery,'' said Swedish cancer specialist Dr. Lars E. Rutqvist, who reported the other study at the ASCO meeting.

In the Swedish study, 3,900 women with early-stage breast cancer were treated with tamoxifen for two or five years following surgery.

After two years, 3,500 were alive and had no recurrence of their cancer. At that point, the women were randomly assigned to two groups; one stopped taking tamoxifen, and the other continued treatment for another three years, said Rutqvist, director of the oncology center at Karolinska Hospital in Stockholm.

After 10 years of follow-up, 80 percent of the patients who took tamoxifen for five years remain alive, and 73 percent have had no disease recurrence, said Rutqvist.

But a preliminary analysis of 800 patients in his study showed only six cases of endometrial cancer in the 5-year group compared with two cases in women who stopped tamoxifen after two years.

Overall, 30 cancers occurred in the 5-year group vs. 24 in the two-year group, Rutqvist said.

``The problem with secondary cancers does not offset the benefit of tamoxifen on breast-cancer survival,'' he added.

Fisher reported findings on 1,200 women who were randomly assigned to take tamoxifen for 10 years, or who stopped treatment after five years. All the women studied were in the early stages of the disease that had not spread to the lymph nodes, and in each case began using tamoxifen after surgical treatment.

All the women had taken tamoxifen for at least five years as part of an earlier study that showed a reduction in mortality and breast-cancer recurrence with five years of tamoxifen, he said. That study was completed in 1988, as part of the National Surgical Adjuvant Breast Project (NSABP), a breast cancer research program sponsored by the National Institutes of Health.

Relatively few women have had recurrences of their cancers or have died during the second phase of the study, but the numbers thus far favor the group that stopped treatment at five years, said Fisher, who is the scientific director of the NSABP, which also sponsored the follow-up study.

Among women who continued tamoxifen for 10 years, 23 have either died and an additional 33 have had breast cancer recurrence.

In the group that stopped tamoxifen after five years, 13 have died and 19 have had disease recurrence, he said.

``These results show that tamoxifen for longer than five years provides no advantage over that observed following tamoxifen withdrawal,'' Fisher said.

As in the Swedish study, longer use of tamoxifen was associated with an increased risk of endometrial cancer, though the overall risk was small: 1.5 percent for the 10-year group and 0.4 percent for the five-year group.

``Certainly, the side effects of tamoxifen do not preclude its use in breast cancer,'' Fisher agreed.

The two studies do not close the door on the question of how long to continue tamoxifen therapy, Rutqvist said.

In his study, the benefits of longer treatment did not begin to appear until four years, and maximum benefits occurred six to eight years after surgery, he said.

Both studies clearly support the use Fof tamoxifen for five years, said Dr. Kent Osborne, a breast-cancer specialist at the University of Texas at San Antonio. Why five years of therapy appears to be best remains unclear, Osborne said.

Breast tumors may slowly adapt to the anti-growth effects of tamoxifen so that the drug becomes ineffective after prolonged use, he suggested.

``We need more studies to confirm that five years is optimal,'' Osborne said.

The risk of endometrial cancer shown in both studies should be viewed in its proper context, commented Dr. Patricia Braly, a professor of obstetrics and gynecology at Louisiana State University Medical Center in New Orleans.

Breast cancer itself increases the risk of endometrial cancer so that separating out the effect of tamoxifen from the inherent risk due to breast cancer would be difficult if not impossible, Braly added.