Search

Involved margins after surgery for early breast cancer increase the risk of local recurrence (LR), but international guidelines suggest that’ no tumour’ on ink is sufficient margin clearance after breast conserving surgery (BCS). Data on the effect of margin clearance on distant recurrence (DR) are lacking. Our aim was to determine the association between margin involvement, recurrence (DR) and breast cancer deaths. Methods Data from breast cancer units in Greater Manchester (GM) and the UK National Cancer Registry (NCRAS) were analysed. Margin status was prospectively recorded after surgery according to National Health Service Breast Screening Pathology (NHSBSP) minimum pathology data standards All patients underwent curative surgery and received adjuvant therapy according to local guidelines. Patients not undergoing curative surgery(T4, inflammatory or metastatic cancer) were excluded .Cox-proportional hazards models investigated factors associated with LR, DR and risk of breast cancer death.NCRAS records breast cancer deaths . Results GM analysis included 3270 patients from 2010 to 2014, 2295 (70.2%) had margins (>2mm) ,302 (9.2%) close (1-2mm) margin clearance and 673 (20.6%) involved (2mm. For Breast Conservation margins1mm (67.5%) and 3,935 (9.6%) were classed as “clear margins” and 9,325 (22.8%) cancer patients had involved margins 1mm were associated with reduced DR and should be essential surgical management. Current guidelines about surgical margins need to be re-evaluated to achieve reduced DR and cancer deaths. Citation Format: Nigel James Bundred, Sarah Michael, John Broggio, Anne Armstrong, Glen Martin, Mohamed Absar, Jane Ooi. Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-01.

Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested. Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic). Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P Conclusions: In summary, niche-independent breast CSC activity measured in vitro by MS assay and in vivo by xenograft growth is not directly correlated with standard clinical parameters. However, both in vitro and in vivo CSC activity are increased in metastatic samples. These results suggest that breast CSC activity is independent of other prognostic indicators but may predict for poor outcome tumours. Relapse free survival data are maturing and will be presented with analysis of primary tumour ALDH1 expression. Citation Format: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke. Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-02.