Phase III Study of Long-Term Prognosis of Estrogen Receptor-Positive Early Breast Cancer Treated with Neoadjuvant Endocrine Therapy With/without Adjuvant Chemotherapy.

Purpose Neoadjuvant endocrine therapy (NET) is a treatment option for estrogen receptor-positive (ER+) postmenopausal early breast cancer (EBC). This phase III trial evaluated the prognosis of EBC patients treated with/without chemotherapy (CT) following NET. Methods ER+/HER2−, T1c-2, and clinically node-negative EBC patients were enrolled in 2008–2013 and treated with endocrine therapy (ET) in weeks 24–28. All patients, excluding those with progressive disease (PD) during NET or ≥ 4 positive lymph nodes after surgery, were randomized to ET for 4.5–5 years with/without CT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant DFS (DDFS), overall survival (OS), and DFS/DDFS/OS according to clinical response to NET. Results Of 904 patients, 669 were randomized to CT+ET ( n = 333) or ET alone ( n = 336). The median follow-up was 7.8 years. DFS (CT+ET, 47 events; ET alone, 70 events) and DDFS did not reach the planned numbers of events. Eight-year DFS/DDFS rates were 86%/93% and 83%/92%, respectively. DFS was significantly better in CT+ET than ET alone in subgroups aged < 60 years ( P = 0.016), T2 ( P = 0.013), or Ki67 > 20% ( P = 0.026). Progesterone receptor and histological grade were predictive markers for clinical responses to NET. Conclusion NET may be used as standard treatment for patients with ER+EBC. Although it is difficult to decide whether to administer adjuvant CT based solely on the effect of NET, the response to NET may help to inform this decision. Trial registration This study was registered at the UMIN Clinical Trials Registry under UMIN000001090 (registered 20 March 2008).