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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: 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. [ABSTRACT FROM AUTHOR]

Purpose Paget's osteosarcoma has a fearful reputation with a quoted survival of at best 5% at 5 years. We therefore reviewed our experience of 26 patients treated over the last 25 years using modern staging and limb salvage techniques to see if there had been any improvement in survival. Subjects: We identified 26 patients on the Royal Orthopaedic Hospital Oncological database with a diagnosis of sarcoma secondary to Paget's disease. Results: The survival rate was 53% at 1 year, 25% at 2 years and no patient survived for 5 years. The median survival was 21 months for those treated with curative intent and 7 months for those treated palliatively. Four of the five patients treated with limb-sparing surgery developed local recurrence between 5 and 12 months, the fifth died at 14 months. There was no difference in survival between amputation and limb salvage. Discussion: The development of sarcomatous change in Paget's disease is well recognised. It represents an important segment of primary bone tumours in patients over 40 years of age. The prognosis is appalling. Indeed only 15 of 368 cases (4%) from a number of historical series have survived more than 5 years. Our results are similarly disappointing with no survivors at 5 years despite modern methods of management of bone tumours. While there is no difference in local recurrence rates or survival between limb reconstruction and limb ablation the poor prognosis for both means that neither can be recommended at present. Sarcomatous change in Pagetoid bone should therefore be regarded as a different disease to primary osteosarcoma. It remains an incurable disease with a poor prognosis. [ABSTRACT FROM AUTHOR]

• SECRAB is the largest chemo-radiotherapy trial to date in early breast cancer. • SECRAB showed a positive therapeutic benefit of using adjuvant synchronous chemo-radiotherapy. • Synchronous chemo-radiotherapy should be used for ≤ 3 week radiotherapy schedules. • SECRAB results are applicable to patients having CMF or anthracycline-CMF schedules. • Overall survival outcome may increase for patients receiving synchronous anthracycline-CMF. The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity. SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893. Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43–0.90; p = 0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26–0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF. Cancer Research UK (CR UK/98/001) and Pharmacia. [ABSTRACT FROM AUTHOR]