NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer
- 1k Downloads
Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE100C or endocrine therapy: letrozole 2.5 mg, daily for 18–23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95 % CI 57–81) were randomised. 12 (54.5, 95 % CI 32.2–75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95 % CI 36.4–79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2–4 and at surgery [fold change: 0.24 (95 % CI 0.12–0.51) and 0.24; (95 % CI 0.15–0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95 % CI 1.47–3.00), letrozole 1.47(95 % CI 0.98–2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95 % CI 1.56–4.41), letrozole 0.95 (95 % CI 0.71–1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.
KeywordsBreast Neoadjuvant therapy Ki-67 cfDNA miRNA
We thank the women who took part in this study; the doctors, nurses and support staff at the following local sites: Asan Medical Centre (27 patients), Charing Cross Hospital (3 patients), St Mary’s Hospital (3 patients), Bristol Haematology and Oncology Centre(2 patients), Guys and St Thomas (2 patients), Aberdeen Royal Infirmary (1 patient), Ninewells Hospital and Medical School, Dundee (4 patients), West Middlesex University Hospital (1 patient), Royal Alexandra Hospital (1 patient). The following sites were open but did not recruit any patients, The Beatson West of Scotland Cancer Centre, Southampton University Hospitals Trust, Crosshouse and Ayr Hospitals and Inverclyde Hospital. We also thank the members of the study steering committee and the independent data monitoring committee. NEOCENT was an NIHR Clinical Research Network portfolio trial, and we acknowledge the help of the local research networks that supported recruitment at UK sites. The study was supported by Cancer Research UK through CTAAC award (Grant No. C37/A9356), a Clinical and Translational Research Committee Programme Award (Grant No. C14315/A13462), and the ECMC network as well as an educational grant from Novartis. Carlo Palmieri was a recipient of a Cancer Research UK Clinician Scientist Award and Basma Rghebi is supported by the Lybian Government. The ICR-CTSU also receives core funding from Cancer Research UK. Dundee recruitment was supported by the Grant Simpson Trust. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Conflict of interest
S.B. Kim received research funding from Novartis unrelated to this study. Remaining authors have no conflicts of interests to declare.
- 4.Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMedCrossRefGoogle Scholar
- 7.Viale G, Regan MM, Maiorano E et al (2008) Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors–International Breast Cancer Study Group. J Clin Oncol 26:1404–1410PubMedCrossRefGoogle Scholar
- 8.Pagani O, Gelber S, Simoncini E et al (2009) Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93. Breast Cancer Res Treat 116:491–500PubMedCentralPubMedCrossRefGoogle Scholar
- 12.Cataliotti L, Buzdar AU, Noguchi S et al (2006) Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative “Arimidex” Compared to Tamoxifen (PROACT) trial. Cancer 106:2095–2103PubMedCrossRefGoogle Scholar
- 13.Krainick-Strobel UE, Lichtenegger W, Wallwiener D et al (2008) Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: a phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy. BMC Cancer 8:62PubMedCentralPubMedCrossRefGoogle Scholar
- 14.Early Breast Cancer Trialists’ Collaborative G, Davies C, Godwin J et al.(2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784Google Scholar