Improved surgical outcomes for breast cancer patients receiving neoadjuvant aromatase inhibitor therapy: results from a multicenter phase II trial

Abstract

Background: Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer. A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice.

Study design: One hundred fifteen postmenopausal women with >2 cm, estrogen receptor (ER) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation.

Results: One hundred six patients were eligible for primary analysis, 96 underwent operations, 7 received chemotherapy after progressive disease, and 3 did not undergo an operation. Baseline surgical status was marginal for breast-conserving surgery (BCS) in 48 (45%), 47 were definitely ineligible for BCS (44%), and 11 were inoperable by standard mastectomy (10%). Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62%, with 12% experiencing progressive disease. Fifty percent underwent BCS, including 30 of 46 (65%) patients who were initially marginal for BCS and 15 of 39 (38%) patients who were initially ineligible for BCS. All 11 inoperable patients successfully underwent operations, including 3 (27%) who had BCS. Nineteen percent of patients undergoing mastectomy had a pathologic T1 tumor, suggesting that some highly responsive tumors were overtreated surgically.

Conclusions: Neoadjuvant aromatase inhibitor improves operability and facilitates BCS, but there was considerable variability in responsiveness. Better techniques to predict response, determine residual tumor burden before operation, and greater willingness to attempt BCS in responsive patients could additionally improve the rate of successful BCS.

Figure 1

This Consolidated Standards of Reporting Trials (CONSORT)–type diagram summarizes patient progress though the protocol. †Six patients withdrew consent, two patients were ineligible on additional investigation and one patient died before receipt of study drug. *Fourteen patients were treated on a protocol defined extension to 24 weeks for patients experiencing a partial response at 16 weeks who were thought to potentially benefit from additional tumor regression. ^§One patient refused operation and two patients did not have operations because of severe intercurrent illness unrelated to study drug. AI, aromatase inhibitor; BCS, breast-conserving surgery; CTX, chemotherapy treatment; ER, estrogen receptor; M, mastectomy.

Figure 2

Pathologic T stage for neoadjuvant aromatase inhibitor treated patients (n = 96) separated by operative outcomes. Ninety-six patients had operations after neoadjuvant endocrine therapy alone, of whom 48 had breast-conserving surgery (BCS) (dark bars) and 48 had mastectomy (light bars). Pathologic stage was determined by American Joint Committee on Cancer criteria.

Figure 3

Waterfall plots for (A) clinical response (Response Evaluation Criteria in Solid Tumors [RECIST]), (B) ultrasonography response RECIST, and (C) mammography RECIST response from central measurements. Response data, as percentage change from baseline are plotted as a sorted continuous feature. Solid symbols, patients who underwent mastectomy; open symbols, patients who underwent breast conservation; circles, pathologic T1/0 disease; diamond T2 disease; triangle T3; square T4.