Aromatase inhibitors may prevent mastectomy in some breast cancers

Issue: June 10, 2011

Recent data from Washington University in St. Louis have shown that aromatase inhibitors can shrink tumors and reduce mastectomy rates among patients with stage II or III breast cancer.

According to Matthew J. Ellis, MD, PhD, of Washington University School of Medicine in St. Louis and investigator of the current trial conducted by the American College of Surgeons Oncology Group, patients with larger breast tumors have two options. “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 said in a press release.

In their study, Ellis and colleagues demonstrated that postmenopausal women with ER-positive breast cancer can benefit from aromatase inhibitors because of their ability to slow or stop the growth of tumors in these women.

The study included 352 women who were randomly assigned to receive one of three FDA-approved aromatase inhibitors: letrozole, anastrozole or exemestane. Letrozole and anastrozole were slightly superior to exemestane in shrinking tumors. But there were no other differences between the three drugs in surgery rates and the Ki67 cell proliferation biomarker.

After 16 weeks of treatment, of the 159 women in the trial who originally required mastectomy, 81 saw sufficient tumor shrinkage to undergo breast-conserving surgery.

“At the beginning, all of these patients were going to get mastectomy, and at the end of the trial only half got mastectomy,” Ellis said. “That’s a very substantial improvement in surgical outcomes.”

In addition, of the 189 women originally considered “marginal” for breast conservation, 83% saw enough tumor regression to undergo breast conserving-surgery rather than mastectomy. Four patients were originally classified as inoperable because mastectomy would not remove all the cancer; however, of these, three saw enough tumor regression to undergo breast-conserving surgery and only one received mastectomy.

Unlike traditional chemotherapy, aromatase inhibitors do not have toxic adverse effects. And for this particular group of patients, Ellis said it is well established that aromatase inhibitors are more active in preventing relapses than chemotherapy.

“These aromatase inhibitors were subject to a lot of debate as to whether one was better than another,” Ellis said. “We found some minor differences in the amount of tumor shrinkage the patients experienced. But there was no difference between the three drugs in terms of how effectively they stopped the tumor growing.”

He said findings from this smaller trial were comparable to larger, more expensive trials designed to compare the same drugs. However, instead of looking at the final outcome in the larger trials, Ellis stressed the importance of using biomarkers such as the Ki67 measure of cell division to look at the tumors’ biological response to the drugs.

“If we can show the drugs are biologically equivalent with a few hundred patients, we should not waste our time with superiority trials involving thousands of patients comparing the same agents,” he said.

Despite the improved surgical outcomes for some patients in this trial, Ellis said many women still required mastectomy because they do not respond to treatment.

“The biggest question in my mind is how best to treat the aromatase inhibitor-resistant patients,” he said. “These patients have poor outcomes, and currently, there is no known targeted therapy for them. The question of aromatase inhibitor resistance is a critical issue to understand and address therapeutically.”

To determine why certain tumors are resistant to these drugs, Ellis and colleagues at Washington University’s Genome Institute recently reported the complete tumor and healthy DNA sequences of 50 patients with breast cancer enrolled in this trial, according to the press release. Twenty-six of the 50 tumors responded to treatment and 24 tumors did not.

“The patients gifted a sample of their tumor to the study and, because we know whether a tumor is responsive or resistant, we can start doing really profound studies to understand the molecular basis for variation in response,” he said. “Ultimately, we hope the genomics instruct which new drugs to use to develop more effective treatment strategies.”

For more information:

Ellis MJ. J Clin Oncol. 2011; [Published online ahead of print May 9, 2011].

Follow HemOncToday.com on Twitter.