A large, multicenter, randomized Phase II trial found that selecting postmenopausal breast cancer patients for aromatase inhibitor (AI) therapy based on high estrogen receptor (ER) expression in tumors resulted in high rates of response and improvements in breast conservation surgery.

Researchers found that for postmenopausal women with ER-rich tumors who are poor candidates for breast conservation therapy and are facing mastectomy, neoadjuvant AI therapy may allow women to undergo lumpectomy in 50 percent of them cases instead.

"High tumor ER levels provide a way to select patients who will do well with this [breast conservation] treatment approach," said lead author John Olson, M.D., Ph.D., associate professor of surgery and chief of the section of endocrine, breast and oncologic surgery at Duke University in Durham, N.C. "These results may raise awareness that neoadjuvant endocrine therapy can be an effective option for women who want a chance to have breast conserving surgery after being told mastectomy is the only surgical option at diagnosis."

While AI therapy has previously been shown to be effective in reducing breast tumors and enabling postmenopausal women to undergo breast-conserving surgery, many physicians lack experience in this approach in the United States and employ chemotherapy instead. In addition, there is uncertainty about which of the three FDA-approved AIs should be used for a definitive clinical trial that would compare chemotherapy and endocrine therapy.

In this American College of Surgeons Oncology Group (ACOSOG) study, researchers randomized the treatment of 374 postmenopausal women with clinical stage II/III ER-rich breast cancer to 16 weeks of therapy with one of three AIs: exemestane, letrozole, or anastrozole. All of the participants at the time of enrollment were poor candidates for breast conservation surgery because of large tumor size. Roughly half of the patients were judged to be marginal candidates while the other half of patients were ineligible and were only candidates for mastectomy. Four women were considered inoperable.

After 16 weeks, 70.9 percent of those who received letrozole, 66.7 percent who were given anastrozole and 60.5 percent of the patients given exemestane had partial or complete clinical responses, respectively. The progression rate was 7.3 percent for those who received anastrozole, 6.5 percent for the exemestane patients, and 4.7 percent for the letrozole group. After therapy, 82 percent (163/199) of the marginal group were able to undergo breast conservation surgery. In addition, approximately half (77/152, or 51 percent) of the mastectomy group and 75 percent (3/4) of the inoperable group could have conservation surgery.

The investigators are now considering a Phase III study comparing chemotherapy to AI therapy to see which is more effective in reducing tumor size prior to surgery.