Breast Cancer Research and Treatment

, Volume 148, Issue 3, pp 581–590 | Cite as

NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer

  • C. Palmieri
  • S. Cleator
  • L. S. Kilburn
  • S. B. Kim
  • S.-H. Ahn
  • M. Beresford
  • G. Gong
  • J. Mansi
  • E. Mallon
  • S. Reed
  • K. Mousa
  • L. Fallowfield
  • M. Cheang
  • J. Morden
  • K. Page
  • D. S. Guttery
  • B. Rghebi
  • L. Primrose
  • J. A. Shaw
  • A. M. Thompson
  • J. M. Bliss
  • R. C. Coombes
Clinical Trial

Abstract

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.

Keywords

Breast Neoadjuvant therapy Ki-67 cfDNA miRNA 

Supplementary material

10549_2014_3183_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 21 kb)
10549_2014_3183_MOESM2_ESM.docx (57 kb)
Supplementary material 2 (DOCX 56 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • C. Palmieri
    • 1
  • S. Cleator
    • 2
  • L. S. Kilburn
    • 3
  • S. B. Kim
    • 4
  • S.-H. Ahn
    • 5
  • M. Beresford
    • 6
  • G. Gong
    • 7
  • J. Mansi
    • 8
  • E. Mallon
    • 9
  • S. Reed
    • 10
  • K. Mousa
    • 10
  • L. Fallowfield
    • 12
  • M. Cheang
    • 3
  • J. Morden
    • 3
  • K. Page
    • 11
  • D. S. Guttery
    • 11
  • B. Rghebi
    • 11
  • L. Primrose
    • 11
  • J. A. Shaw
    • 11
  • A. M. Thompson
    • 13
  • J. M. Bliss
    • 3
  • R. C. Coombes
    • 2
  1. 1.Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK
  2. 2.Division of Cancer, Department of Surgery and CancerImperial College LondonLondonUK
  3. 3.ICR Clinical Trials & Statistics Unit (ICR-CTSU)The Institute of Cancer ResearchSuttonUK
  4. 4.Department of Oncology, Asan Medical CentreUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of Breast Endocrine Surgery, Asan Medical CentreUniversity of Ulsan College of MedicineSeoulKorea
  6. 6.Department of Clinical OncologyRoyal United HospitalBathUK
  7. 7.Department of Pathology, Asan Medical CentreUniversity of Ulsan College of MedicineSeoulKorea
  8. 8.Department of Medical OncologyGuy’s and St Thomas’ Hospital and King’s College London Biomedical Research CentreLondonUK
  9. 9.University Department of Pathology, College of Medical, Veterinary and Life of SciencesUniversity of Glasgow, Royal and Western InfirmariesGlasgowUK
  10. 10.Imperial Clinical Trials Unit-Section on CancerImperial College LondonLondonUK
  11. 11.Department of Cancer Studies and Molecular MedicineUniversity of LeicesterLeicesterUK
  12. 12.SHORE-C, Brighton and Sussex Medical SchoolUniversity of SussexFalmerUK
  13. 13.Department of Surgical OncologyMD Anderson Cancer CenterHoustonUSA

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