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Tamoxifen may increase the risk of later tumours being more aggressive

Scott Gottlieb New York

If a woman who takes tamoxifen for breast cancer develops a cancer in her other previously healthy breast, the risk is higher that it will be of a more dangerous type than a contralateral cancer in a woman who has never taken the drug.

Researchers collected data on 8981 women with primary unilateral breast cancer aged at least 50 who had received adjunctive hormonal therapy but not chemotherapy (tamoxifen users) or had received neither hormonal therapy nor chemotherapy (tamoxifen non-users) (Journal of the National Cancer Institute 2001;93:1008-12).

The researchers identified contralateral breast cancers in 89 of the tamoxifen users and 100 of the non-users. Of these 189 women, 112 had oestrogen receptor positive tumours, 20 had oestrogen receptor negative tumours, and 57 had undetermined tumour types.

Of the 20 women with the more dangerous oestrogen receptor negative tumours, 17 had taken tamoxifen after their first breast cancer whereas three had not. Compared with tamoxifen non-users, the hazard ratio among tamoxifen users of developing an oestrogen receptor positive contralateral tumour was 0.8 and of developing an oestrogen receptor negative contralateral tumour was 4.9. The results suggest that tamoxifen may stimulate the growth of oestrogen receptor negative cells.

"This is a preliminary study. My colleagues and I do not think these findings should change current therapy," said the study’s lead author, Dr Christopher Li, an epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle. He said that he hoped the results would stimulate further research on tamoxifen.

More than half of the nearly 200 000 American women in whom breast cancer is diagnosed each year will eventually take tamoxifen. The drug has been shown to suppress the growth of any cancer cells that may remain after the original tumour is surgically removed.

Tamoxifen works by blocking the receptor, preventing oestrogen from landing and stimulating cell growth. Oestrogen receptor negative breast cancers, however, are impervious to the effects of tamoxifen and in general are harder to treat than positive tumours, largely for that reason. Women whose tumours are negative therefore have a poorer prognosis, with up to a 30% higher risk of dying in the five years after initial diagnosis, than women with positive cancers.

Sandra Swain, chief of the medicine branch of the National Cancer Institute, questioned the findings in an accompanying editorial (pp 963-5). The study was not a randomised controlled trial. In addition, she wrote, the small number of cases in the study makes the findings statistically shaky.

"Consequently," Dr Swain wrote, "the study does not provide reliable evidence that is sufficient to make any conclusions regarding the estrogen receptor status of contralateral breast cancer in women treated with tamoxifen."

"I just don’t put any faith in the results," she said. "The results of this study should not change practice at all. Women should not be afraid to take tamoxifen based on this study," she wrote.