Morphological and molecular changes following neoadjuvant endocrine therapy of ER positive breast cancer: implications for clinical practice.

Badr, Nahla M; Spooner, David; Steven, Jane; Stevens, Andrea; Shaaban, Abeer M

BACKGROUND Neoadjuvant endocrine therapy (NAET) is used in the management of estrogen receptor positive (ER+) 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. MATERIAL AND METHODS 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. RESULTS Two carcinomas (both of lobular type) achieved complete pathological response. Central scarring was seen in 49.3% of tumours post-treatment. Significant changes in tumour type (41.6%), grade (downgrading in a third of tumours), PR expression (22.3%) with a switch to PR negative status in 17.6% of cases were observed. The latter was associated with absence of tumour infiltrating lymphocytes (p=0.005). 10% of cases showed a change in HER2 expression (p=0.002). 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.