Estrogen Tumors May Hold Breast Cancer Clues

Study Could Direct Treatment to Endocrine Therapy

Knowing which patients have breast cancer tumors that use estrogen to fuel their growth may help to predict who will benefit from chemotherapy treatment, say researchers at M. D. Anderson.

Their study, presented last month at the San Antonio Breast Cancer Symposium, could change the way breast cancer is treated in the future.

Today, patients routinely receive chemotherapy as their first treatment, followed by surgery. Patients with the estrogen-fueled tumors may someday receive endocrine therapies that block the estrogen action or production (through drugs like tamoxifen, anastrozole, letrozole or exemestane), or interfere with the hormonal pathways (with drugs such as fulvestrant.)

"We hope this study will help to direct the best treatment for patients," says the study's author, Aman Buzdar, M.D., professor in the Department of Breast Medical Oncology at M. D. Anderson. "In the future, we may be able to identify patients who will do well with endocrine therapies alone."

Buzdar and a team of researchers looked at tumor samples of 1,018 patients followed at the center since 1975 in which the estrogen receptor status was known. All patients received chemotherapy and surgery.

Estrogen receptor status is determined through a special test on the cancer cell that shows if a breast cancer is likely to benefit from endocrine therapy. Receptors are proteins present in cancer cells that, through complex interactions with hormones, can maintain the growth of cancer. By interfering with these protein pathways, doctors can slow or stop the growth of the cancer.

The investigators looked for the evidence of a complete "pathological response" to treatment (a situation in which there was no invasive cancer left either in the breast or in the lymph nodes). They separated the results by estrogen receptor status.

They found that:

More than 20% of patients with estrogen-negative breast cancer had no cancer left after treatment. (Estrogen-negative cancer lacks the receptors on cancer cells and doesn't respond to endocrine therapies).

Five percent of patients with estrogen-positive cancer had no cancer left following treatment. (Estrogen-positive cancer has the receptors on cancer cells, making them more likely respond to endocrine therapies).

"It didn't matter what kind of chemotherapy was used, there was more benefit observed in patients with estrogen receptor-negative cancers," says Buzdar. "Even though a significant number of estrogen-positive patients had clinical regression in their tumors, there was not the same numbers of pathological complete response."

Buzdar says that because these two breast cancer subtypes behave in dissimilar ways, they also respond differently to chemotherapy treatment. "Estrogen negative cancers are more poorly differentiated and tend to be more sensitive to chemotherapy drugs, and are easier to kill with chemotherapy," he says. "Estrogen receptor-positive breast cancers are differentiated and tend to be less responsive to chemotherapy.

"These results support what has been suspected. Breast cancer patients with estrogen receptor-positive disease may have a better likelihood of response to endocrine therapies, but the role of chemotherapy in this set of patients needs to be further defined," Buzdar continues. "In the future, we may be able to tell who should receive chemotherapy, who should have endocrine treatments, and who might benefit from both."