Efficacy of six month neoadjuvant endocrine therapy in postmenopausal, hormone receptor-positive breast cancer patients--a phase II trial

Abstract

Background: Neoadjuvant hormonal therapy (NHT) is playing an increasing role in the clinical management of breast cancer (BC) and may improve surgical outcomes for postmenopausal, oestrogen receptor (ER)-positive BC patients. However, there is currently no consensus on the optimal duration of NHT before surgery. Here, we present the outcomes of the TEAM IIA trial, a multicentre, phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal, strong ER-positive (ER+, ⩾50%) BC patients.

Methods: 102 patients (stage T2-T4ac) were included in the study after exclusion of ineligible patients. Primary end-point was clinical response at 3 and 6 months as measured by palpation. Secondary end-point was radiological response as measured by magnetic resonance imaging (MRI), mammography and/or ultrasound. Linear mixed models (95% confidence interval (CI)) were used to compare changes in mean tumour size (in mm) between baseline, 3 and 6 months after the start of endocrine therapy. Conversion rates from mastectomy to breast conserving surgery (BCS) were evaluated.

Results: Median age of all patients was 72 years (range 53-88). Overall response rate by clinical palpation was 64.5% in all patients with a final palpation measurement. Four patients had clinically progressive disease. 63 patients had both 3-month and >3-month palpation measurements. Overall response was 58.7% at 3 months and 68.3% at final palpation (>3 months). Mean tumour size by clinical palpation at T=0 was 39.1mm (95% CI 34.8-43.4mm), and decreased to 23.0mm (95% CI 18.7-27.2mm) and 16.7 mm (95% CI 12.6-20.8) at T=3 and T>3 months, respectively (p=0.001). Final radiological response rates at the end of treatment for MRI (n=37), ultrasound (n=77) and mammography (n=56) were 70.3%, 41.6% and 48.2%, respectively. Feasibility of BCS improved from 61.8% to 70.6% (McNemar p=0.012).

Conclusion: 6 months of neoadjuvant exemestane therapy helps reduce mean tumour size further in strongly ER-positive BC patients without significant side-effects compared to 3 months. Nevertheless, some patients still experience disease progression under exemestane. Feasibility of breast conservation rates improved by almost 10%.

Keywords: Breast cancer; Breast conserving surgery; Endocrine therapy; Exemestane; Neoadjuvant; Postmenopausal; Pre-operative.