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Updated: Nov 22, 2025
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Morphological and molecular changes following neoadjuvant endocrine therapy of oestrogen receptor-positive breast
Nahla M Badr1,2, David Spooner3, Jane Steven3
1Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK.
Aims:
Neoadjuvant endocrine therapy (NAET) is used in the management of oestrogen receptor (ER)-positive breast cancer. The optimal method for histological assessment of response and the effect of NAET on the tumour morphology, grade and molecular profile remain unclear. The aim of this study is to investigate the NAET effect on tumour type, grade and molecular profile by analysing a well-characterised cohort of breast cancer samples in a single large UK tertiary referral centre, and to provide guidance on the pathological assessment of those lesions to inform adjuvant management and prognosis.
Methods And Results:
A single large-institution cohort of 132 patients who received NAET over a 13-year period was identified. Comprehensive clinical, histopathological and follow-up data were collected. A detailed histological review of a subset with residual post-treatment carcinoma was undertaken. Two carcinomas (both of the lobular type) achieved complete pathological response. Central scarring was seen in 49.3% of tumours post-treatment. Significant changes in tumour type (41.6%), tumour grade (downgrading in one-third of tumours), and progesterone receptor (PR) expression (22.3%), with a switch to PR-negative status in 17.6% of cases, were observed. The last of these was associated with an absence of tumour-infiltrating lymphocytes (P = 0.005). Ten per cent of cases showed a change in HER2 expression (P = 0.002). The median patient survival was 60 months, and downgrading of tumours was associated with better overall survival (P = 0.05).
Conclusions:
We propose a histological method for assessment of residual carcinoma following NAET, and recommend repeat ER/PR/HER2 testing to inform management and prognosis.
Insights
Neoadjuvant endocrine therapy (NAET) significantly alters oestrogen receptor-positive breast cancer characteristics, including tumour type, grade, and receptor expression. Repeat testing after NAET is crucial for guiding treatment and prognosis.
Area of Science:
- Oncology
- Pathology
- Endocrinology
Background:
- Neoadjuvant endocrine therapy (NAET) is standard for ER-positive breast cancer.
- Optimal histological assessment of NAET response and its molecular effects are not well-defined.
Purpose of the Study:
- To investigate NAET's impact on breast cancer tumour type, grade, and molecular profile.
- To establish guidance for pathological assessment of NAET-treated lesions.
Main Methods:
- Analysis of a 132-patient cohort treated with NAET over 13 years.
- Detailed histological review of residual post-treatment carcinoma.
- Collection of clinical, histopathological, and follow-up data.
Main Results:
- Complete pathological response in 2 lobular carcinomas.
- Significant changes observed in tumour type (41.6%) and grade (downgrading in one-third).
- Alterations in progesterone receptor (PR) and HER2 expression occurred in a subset of cases, impacting survival.
Conclusions:
- A histological assessment method for residual carcinoma post-NAET is proposed.
- Repeat ER/PR/HER2 testing is recommended to guide adjuvant management and prognosis.
