Second breast cancers may be more difficult to treat in women who take the drug tamoxifen, study suggests

July 03, 2001

SEATTLE - A new study from the Fred Hutchinson Cancer Research Center confirms that tamoxifen use decreases the risk of a second breast cancer, but it also finds that the drug may cause a fivefold increased risk of estrogen-receptor (ER)-negative breast cancer - a cancer that is more difficult to treat - in the breast opposite, or contralateral, to the initial tumor.

The study follows research in recent years indicating tamoxifen improves survival and reduces risk of recurrence among women diagnosed with breast cancer.

Christopher Li, M.D., and colleagues in the Hutchinson Center's Public Health Sciences Division will report their findings tomorrow (July 4) in the Journal of the National Cancer Institute. This population-based study was funded by a grant from The Life Possibilities Fund (see sidebar). Comparing breast-cancer patients who received tamoxifen to those who did not, Li and colleagues found that while the drug appeared to cause a 20 percent reduction in ER-positive contralateral breast cancer - the more common type - it also appeared to increase the risk of ER-negative contralateral tumors by nearly 500 percent.

"Among women who take tamoxifen after an initial breast-cancer diagnosis, our study and numerous random trials suggest that tamoxifen will decrease a woman's risk of developing cancer in the other breast," Li said. "But if they do develop a tumor on the opposite side, our study suggests that the cancer is more likely to be ER negative, which is associated with a higher mortality risk." Li and colleagues' data analysis showed that 27 percent of the contralateral tumors that developed in tamoxifen users were ER negative, while only 4 percent of the contralateral tumors that developed in non-users were ER negative. Li, a postdoctoral fellow in epidemiology at the Hutchinson Center and at the University of Washington School of Public Health and Community Medicine, cautioned that the study shouldn't alter what physicians recommend to their patients.

"While this study, if confirmed by others, adds to our knowledge about the effects of tamoxifen, I do not believe it should change current clinical practices, as tamoxifen has clearly been shown to reduce the risk of recurrence and improve survival among women diagnosed with breast cancer," he said. The majority of breast tumors - about two thirds of those initially diagnosed - are ER positive, which means they need the hormone estrogen to grow. Such tumors respond well to anti-estrogen drugs, such as tamoxifen, which block the receptor, or docking site, to which estrogen can bind, thereby halting the growth of cancer cells. ER-negative tumors, on the other hand, can thrive without estrogen and are therefore unresponsive to estrogen blockers such as tamoxifen.

In addition to being more difficult to treat, ER-negative tumors are associated with a higher mortality rate; women with this type of breast cancer face an 8 percent to 35 percent lower five-year survival rate than those whose tumors are ER positive.

The study population involved nearly 9,000 women in western Washington that were diagnosed between 1990 and 1998 with primary localized or regional-stage cancer in one breast. The women, 50 years or older, were followed until cancer developed in the other breast, they died or the study ended in December 1999. Overall, among the tamoxifen users, 89 developed cancer in the opposite breast; among the non-users, 100 developed a tumor on the other side.

Study data was obtained from the Hutchinson Center's Cancer Surveillance System, a population-based registry of cancer incidence in western Washington.

This is the first population-based study of its kind to address the estrogen-receptor status of contralateral breast tumors among women who have used tamoxifen in the treatment of their breast cancer, said Janet Daling, Ph.D., senior author of the paper.

"Future studies should further evaluate the characteristics of contralateral tumors among women who do and do not receive tamoxifen treatment to increase our understanding of the mechanisms involved," said Daling, a member of the Hutchinson Center's Public Health Sciences Division and a professor of epidemiology at the UW School of Public Health and Community Medicine.

Risks associated with tamoxifen use include an increased risk of endometrial cancer, deep-vein thrombosis (blood clots), pulmonary embolism and cataracts. Benefits associated with tamoxifen include a reduced risk of breast-cancer recurrence and improved survival, reduced risk of bone fractures and a lowering of LDL, or "bad," cholesterol levels.

SIDEBAR

CYCLIST'S AROUND-THE-WORLD TREK FUNDS TAMOXIFEN STUDY Life Possibilities provides seed money for breast-cancer research at the Hutch

Lisa Morgan began her journey New Year's Day 2000 at the Tournament of Roses Parade in Pasadena, Calif. - the first leg of Odyssey 2000, an around-the-world bike trek involving some 250 adventurous souls. While most of the riders regarded the trip as simply a fun, unique way to see the world, Morgan rode as a tribute to Sally Morris, a friend and mentor who in 1998 succumbed to breast cancer. Morgan also rode as a way to raise money for breast-cancer research through Life Possibilities, a grass-roots organization she co-founded with two other friends who knew Morris: Roxi Dixon and Judy Timson of Portland, Ore.

By the time Morgan had completed her global bike tour 11 months and 45 countries later in Singapore, the Life Possibilities team had raised more than a quarter million dollars.

All of the proceeds raised by Life Possibilities provide seed money for promising new breast-cancer research at the Fred Hutchinson Cancer Research Center in Seattle.

One such example is a study by postdoctoral fellow Christopher Li, M.D., and colleagues, to be published tomorrow in the Journal of the National Cancer Institute, which suggests that use of the drug tamoxifen may increase significantly the risk of ER-negative contralateral breast cancer.

Although Morgan, a former Seattle resident who now lives in Atlanta, Ga., biked through every continent except Antarctica, her journey is far from over. Her goal for Life Possibilities: to raise $1 million for the initial development of innovative breast-cancer research at the Hutchinson Center, one of the world's leading cancer-research facilities.

For more information or to make a donation to Life Possibilities, visit www.lifepossibilities.com or call 206-667-4902.

The Fred Hutchinson Cancer Research Center is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the Center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. The Hutchinson Center is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 37 nationwide. For more information, visit the Hutchinson Center's Web site at www.fhcrc.org.

Advancing Knowledge, Saving Lives

Fred Hutchinson Cancer Research Center

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