Morphological and molecular changes following neoadjuvant endocrine therapy of oestrogen receptor‐positive breast cancer: implications for clinical practice

Abstract

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.

Receptor Status after Neoadjuvant Therapy of Breast Cancer: Significance and Implications

“…Unlike NACT, pCR following NAET is uncommon. In their study of 132 HR+ carcinomas, Badr et al [38] reported pCR in only two carcinomas; both of the lobular type. A meta-analysis of 20 NAET trials reported an overall pCR rate of less than 10% [39].…”

“…The Japanese trial “PROACT,” Table 2, reported that 5/40 anastrozole treated and 20/37 tamoxifen treated tumours for 3 months switched profile from ER+ to ER− [43]. A more recent larger UK retrospective single-centre study of 132 paired samples showed only one tumour (0.7%) switching to ER− profile with 5 and 8 cases showing minimal increase or decrease in the Allred score [38].…”

“…Maeda reported loss of PR expression in a 40.1% of 28 paired samples treated with NAET compared with only 8.2% loss following NACT [48]. In a large study of 132 invasive carcinomas, Badr et al [38] reported a highly statistically significant change in PR expression following letrozole therapy with 12.7% switching from positive to negative status (Fig. 1c, d).…”

“…Badr et al [38] showed that a maintained PR profile was associated with better response to NAET ( p = 0.018) and with longer survival compared with the loss of PR expression (107.3 vs. 91.7 months, respectively). Although this difference in survival was not statistically significant, this finding is intriguing and requires validation in large studies.…”

“…1e, f). Badr et al [38] reported a statistically significant change in HER2 status following NAET in 10% of cases ( p = 0.002) with more tumours switching from negative to positive status (8 switched from positive to negative status and 5 from negative to positive expression). The numbers were however too small to allow correlation with the patient outcome.…”