NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.
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.
Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
C
C
Palmieri
S
S
Cleator
L S
LS
Kilburn
S B
SB
Kim
S-H
SH
Ahn
M
M
Beresford
G
G
Gong
J
J
Mansi
E
E
Mallon
S
S
Reed
K
K
Mousa
L
L
Fallowfield
M
M
Cheang
J
J
Morden
K
K
Page
D S
DS
Guttery
B
B
Rghebi
L
L
Primrose
J A
JA
Shaw
A M
AM
Thompson
J M
JM
Bliss
R C
RC
Coombes
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077289:Letrozole; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D035683:MicroRNAs; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; C487931:mirnlet7 microRNA, human; D000077289:Letrozole