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Aims: Standard neoadjuvant endocrine therapy (NAET) is used for 6–9 months to downstage hormone‐receptor‐positive breast cancer. Bridging ET was introduced during the COVID‐19 pandemic to delay surgical intervention. There are no data in the literature on the effect of short course therapy on tumour response. We aimed to analyse the effect of bridging ET and validate the previously proposed neoadjuvant ET pathological reporting criteria. Methods and Results: This was a multicentre cohort of 256 patients who received bridging ET between March and October 2020. Assessment of paired pre‐ and post‐NAET hormone receptors and HER2 and posttherapy Ki67 expression was done. The median duration of NAET was 45 days. In all, 86% of cases achieved partial pathological response and 9% showed minimal residual disease. Histological response to ET was observed from as early as day 6 posttherapy. Central scarring was noted in 32.8% of cases and lymphocytic infiltrate was seen in 43.4% of cases. Significant changes associated with the duration of ET were observed in tumour grade (21%), with downgrading identified in 12% of tumours (P < 0.001), progesterone receptor (PR) expression with switch to PR‐negative status in 26% of cases (P < 0.001), and HER2 status with a switch from HER2‐low to HER2‐negative status in 32% of cases (P < 0.001). The median patient survival was 475 days, with an overall survival rate of 99.6%. Conclusions: Changes characteristic of tumour regression and significant changes in PR and HER2 occurred following a short course of NAET. The findings support biomarker testing on pretreatment core biopsies and retesting following therapy. [ABSTRACT FROM AUTHOR]

Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p < 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p < 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma. [ABSTRACT FROM AUTHOR]

Aims Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively newly described pathological lesion that is distinguished from classical LCIS by its large pleomorphic nuclei. The lesion is uncommon and its appropriate management has been debated. The aim of this study is to review data from a large series of PLCIS to examine its natural history in order to guide management plans. Materials and methods Comprehensive pathology data were collected from two cohorts; one from a UK multicentre audit and the other a series of PLCIS cases identified from within the GLACIER study cohort. 179 cases were identified of whom 176 had enough data for analysis. Results Out of these 176 cases, 130 had invasive disease associated with PLCIS, the majority being of lobular type (classical and/or pleomorphic). A high incidence of histological grade 2 and 3 invasive cancers was noted with a predominance of ER positive and HER-2 negative malignancy. When PLCIS was the most significant finding on diagnostic biopsy the upgrade to invasive disease on excision was 31.8%, which is higher than pooled data for classical LCIS and DCIS. Conclusion The older age at presentation, high grade of upgrade to invasive cancer, common association with higher grade tumours suggest that PLCIS is an aggressive form of insitu disease. These findings support the view that PLCIS is a more aggressive form of lobular in situ neoplasia and supports the tendency to treat akin to DCIS. [ABSTRACT FROM AUTHOR]