St. Louis, MO. -- Researchers at Washington University School of Medicine in St. Louis have discovered a way to quickly tell if women with advanced breast cancer are responding to hormone therapy. The finding could reduce the need for harsher chemotherapy.
Two-thirds of women with breast cancer have tumors that can bind estrogen, and about half of those whose cancer has spread beyond the breast will respond to hormonal therapy. However, many doctors switch patients from anti-estrogens and other hormones to toxic chemical agents because it is difficult to determine if estrogen inhibitors are working.
The researchers have found that positron emission tomography (PET) reveals whether anti-estrogens such as tamoxifen are effective. ''With this imaging method, we can predict within about a week of starting therapy if women will likely respond,'' says Farrokh Dehdashti, M.D., an imaging specialist and assistant professor of radiology at the medical school's Mallinckrodt Institute of Radiology. Doctors would normally wait several months for signs of tumor shrinkage.
Dehdashti led a study of 11 women with metastatic breast cancer. Her team is announcing the results today at the annual meeting of the Radiological Society of North America in Chicago. Joanne E. Mortimer, M.D., clinical director of the Division of Medical Oncology, served as primary physician in the study.
Mortimer, who also is an associate professor of medicine and medical oncology, says that one-third of doctors shift patients from hormonal therapy to chemotherapy because tumors often have an initial growth response to the drugs called a flare reaction. The patients may appear to be worse with this reaction, a situation that is indistinguishable from tumor progression.
Anti-estrogens block hormone action by occupying the sites on breast cancer cells that are normally used by estrogen. At first, the tumors fail to distinguish between bound estrogen and anti-estrogens. The flare reaction can occur weeks or months later, before a period of tumor shrinkage sets in. It leaves no tell-tale sign, forcing doctors to switch therapies or risk that tumor growth signals cancer progression. Switching therapies can be a mistake, Mortimer says. ''Although chemotherapy does make tumors shrink and patients feel better, they do not live longer. In contrast, women with estrogen-sensitive breast cancer can do well for years on hormone treatment,'' she says. ''It's a huge quality-of-life issue.''
Dehdashti notes that the findings also have implications for women who don't respond to anti-estrogens because it could indicate the need to change therapies. ''This approach should make treatment more individualized for each woman's situation,'' she says.
With PET, investigators can track the location of radioactively labeled molecules that interact with cells. In the breast cancer study, the researchers used a method called FES-PET (fluoro-estradiol-PET) to determine if labeled estrogen bound to and ''lit up'' tumor cells, knowing that such cells could bind tamoxifen. Another method, called FDG-PET, provided images of tumor growth by measuring the cells' uptake of a radiolabeled form of glucose. The two techniques allowed the researchers to determine tamoxifen's effectiveness. In seven of the women, it bound well to their tumors, which grew rapidly seven to 10 days after treatment began, though the women were unaware that they had flare reactions.
Months after treatment, the seven women's tumors had shrunk, whereas the four women whose tumors failed to bind tamoxifen showed no signs of a flare reaction or response to treatment. Therefore, the researchers concluded that images of tamoxifen binding and tumor growth can predict whether the drug is working. The researchers have obtained similar findings from 14 women in a follow-up study that still is underway.
Mortimer calls these early results exciting even though the current cost of PET imaging can be thousands of dollars. ''Tamoxifen is the most commonly used anti-cancer agent worldwide, and many women with breast cancer are already benefiting from its use,'' she says.
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A grant from the National Institutes of Health funded this study.