The Clinical Impact of Neoadjuvant Endocrine Treatment on Luminal-like Breast Cancers and Its Prognostic Significance: Results from a Single-Institution Prospective Cohort Study

Abstract

Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast- conserving surgery (BCS) rates, provides an opportunity for us to assess in vivo NET effectiveness, and allows us to study any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness. Methods: From 2016 to 2020, a single-institution cohort of patients, treated with NET and further surgery, was evaluated. In patients with Ki67 ≥ 10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered. Results: A total of 115 estrogen receptor-positive (ER+)/HER2-negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0–6.0). The median maximum size in the surgical sample was 40% smaller than the pretreatment size measured by ultrasound (p < 0.0001). The median pretreatment Ki67 expression was 20.0% (IQR: 12.0–30.0), and was reduced to 5.0% (IQR: 1.8–10.0) after four weeks, and to 2.0% (IQR: 1.0–8.0) in the surgical sample (p < 0.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold change after four weeks was significantly related to a PEPI score of zero (p < 0.002). No differences were observed between luminal A- and B-like tumors, with regard to fold change and PEPI score. Conclusions: In our cohort, NET was proven to be effective for tumor size and Ki67 downstaging. This resulted in a higher rate of conservative surgery, aided in therapeutic decision making, provided prognostic information, and constituted a safe and well-tolerated approach.

A prospective study on tumour response assessment methods after neoadjuvant endocrine therapy in early oestrogen receptor positive breast cancer

“…Only one case of pCR after NET was recorded and most cases (72%) showed partial path-TR (Table 2). These results are in agreement with the response rates obtained in similar series (Martí et al 2022;Lerebours et al 2016;Skriver et al 2018).…”

“…Only one case of pCR after NET was recorded and most cases (72%) showed partial path-TR (Table 2). These is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) results are in agreement with the response rates obtained in similar series (Martí et al 2022;Lerebours et al 2016;Skriver et al 2018).…”

“…Ki67, ER and PgR expression was assessed in all tumours pre-and post-treatment. As seen in previous studies using similar cohorts (Toi et al 2011;Martí et al 2022), NET significantly decreased all these three parameters, being the changes in Ki67 and PgR the most significant (both p < 0.0001) (Table 1 and supplementary material, Figure S1). Regarding to surgical management, 95 patients (90%) underwent a BCS after NET, while in 10 patients (10%) a modified radical mastectomy was performed.…”

“…Three pioneer clinical trials (IMPACT, PROACT and P024) demonstrated that NET is effective in downsizing ER+ BC and facilitating breast-conserving surgery (BCS), also showing a greater efficacy for aromatase inhibitors compared with tamoxifen (Eiermann et al 2001; Cataliotti et al 2006; I. E. Smith et al 2005). These and another results have provoked the inclusion of NET as a recommendation in international guidelines, particularly for postmenopausal women presenting ER+ BC given for 4-8 months (Korde et al 2021; Martí et al 2022; Cardoso et al 2019). An important advantage of NET is that it allows “in vivo” evaluation of response, hence granting real-time examination of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation.…”

Promoter hypomethylation and overexpression of TSTD1 mediate poor treatment response in breast cancer

“…Tamoxifen is one of the most commonly used hormone therapies for breast cancer. However, hormonal therapy resistance was apparent in 30-40% cases ( 22 , 23 ), and takes a long time to complete ( 24 ). TNBC has a poor prognosis, largely due to the lack of targeted treatments.…”