Estrogen-Lowering Drugs Reduce Mastectomy Rates for Breast Cancer Patients

In the first large trial of its kind in the United States, researchers have shown that estrogen-lowering drugs can shrink tumors and reduce mastectomy rates for patients with stage 2 or 3 breast cancer.

Patients with these larger breast tumors have two options, says Matthew J. Ellis, MD, PhD, of Washington University School of Medicine in St. Louis and principal investigator of the trial conducted by the American College of Surgeons Oncology Group. “One option is to undergo mastectomy. The second is to receive medication before surgery to reduce the size of the tumor so that breast-conserving surgery becomes possible,” he says.

Those who choose the second option usually receive chemotherapy. But now, Ellis and colleagues have shown that post-menopausal women with estrogen-receptor positive breast cancer can benefit from a class of drugs called aromatase inhibitors that lower the amount of estrogen in the body. Since estrogen-receptor positive breast cancers feed off estrogen, aromatase inhibitors can slow or stop the growth of these tumors in women who have undergone menopause.

Though estrogen no longer comes from the ovaries, post-menopausal women still make small amounts of estrogen with the enzyme aromatase. Aromatase inhibitors block this enzyme, eliminating the body’s remaining estrogen. Because aromatase inhibitors don’t stop the ovaries from making estrogen, they only work in post-menopausal women.

The results appear online May 9, in the Journal of Clinical Oncology.

Of the 159 women in the trial who were originally told they required mastectomy, 81 or slightly more than half saw sufficient tumor shrinkage after 16 weeks of aromatase inhibitor treatment to undergo breast-conserving surgery instead.

“At the beginning, all of these patients were going to get mastectomy and at the end of the trial only half got mastectomy,” says Ellis, also an oncologist who treats patients at the Alvin J. Siteman Cancer Center at Washington University and Barnes-Jewish Hospital. “That’s a very substantial improvement in surgical outcomes.”

In addition, of the 189 women originally considered “marginal” for breast conservation (because it would likely be disfiguring), 83 percent saw enough tumor regression to undergo breast conserving-surgery rather than mastectomy. And of the four patients originally classified as inoperable (because mastectomy would not remove all the cancer), three saw enough tumor regression to undergo breast-conserving surgery and only one received mastectomy.

Beyond these benefits, aromatase inhibitors do not have the toxic side effects of traditional chemotherapy. And for this particular group of patients, Ellis says it is well established that aromatase inhibitors are more active in preventing relapses than chemotherapy.

In all, 352 women were randomly assigned to receive one of three FDA-approved aromatase inhibitors – letrozole, anastrozole and exemestane. Letrozole and anastrozole were slightly better than exemestane in shrinking tumors. But there were no other differences between the three drugs in surgery rates and in a key measure of how well the drugs stopped cancer cells from dividing, called the Ki67 cell proliferation biomarker.