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

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.

Efficacy and acceptability of neoadjuvant endocrine therapy in patients with hormone receptor‐positive breast cancer: A network meta‐analysis

“…RTC: nonrandomised controlled trial ZHANG ET AL. | 12395 Ellis et al, 2011;Fasching et al, 2014;Guarneri et al, 2014;Hojo et al, 2013;Lerebours et al, 2016;Palmieri, Cleator, et al, 2014;Polychronis et al, 2005;Saura et al, 2017;Smith et al, 2005Smith et al, , 2007 met our inclusion criteria and were included in our network metaanalysis.…”

“…Most trials had an unclear risk of bias. For the blinding of participants and personnel, six studies (Alba et al, 2012;Baselga et al, 2009;Ellis et al, 2011;Fasching et al, 2014;Hojo et al, 2013;Palmieri, Cleator, et al, 2014) were at a high risk of bias and seven studies (Baselga et al, 2009;Cataliotti et al, 2006;Eiermann et al, 2001;Guarneri et al, 2014;Polychronis et al, 2005;Saura et al, 2017;Smith et al, 2005) were at a low risk of bias. However, for the blinding of outcome assessments, only two studies (Polychronis et al, 2005;Smith et al, 2005) had a low risk of bias.…”

Exploring circulating micro‐RNA in the neoadjuvant treatment of breast cancer

“…Recently the radiological and clinical response of breast cancer to either neoadjuvant chemotherapy or hormonal therapy was assessed using a low density miRNA array. Significantly increased Let‐7a was found in the plasma of patients achieving a radiological response following neoadjuvant chemotherapy, but not hormonal therapy …”

“…Significantly increased Let-7a was found in the plasma of patients achieving a radiological response following neoadjuvant chemotherapy, but not hormonal therapy. 117 In breast cancer tissue, down-regulation of miR-200c was found in patients who were non-responsive to NAC. 110 Subsequently, up-regulation of miR-200c in human breast cancer cell lines enhanced chemosensitivity and decreased expression of multi-drug resistance (MDR) proteins P-glycoprotein (Pgp) and MDR-associated protein (MRP-1).…”

Neoadjuvant endocrine therapy for luminal breast cancer treatment: a first-choice alternative in times of crisis, such as the COVID-19 pandemic

“…Evidence for supporting this approach is quite strong. Robust (although relatively small) trial data show preoperative endocrine treatment to be a safe option when compared to chemotherapy [4][5][6], with significantly lower toxicity. The rates of breast conserving surgery increase clearly with NET, reaching 60%-80% [7][8][9].…”