Oxygen Levels Do Not Determine Radiation Survival of Breast Cancer Stem Cells

For more than a century oxygen has been known to be one of the most powerful radiosensitizers. However, despite decades of preclinical and clinical research aimed at overcoming tumor hypoxia, little clinical progress has been made so far. Ionizing radiation damages DNA through generation of free radicals. In the presence of oxygen these lesions are chemically modified, and thus harder to repair while hypoxia protects cells from radiation (Oxygen enhancement ratio (OER)). Breast cancer stem cells (BSCSs) are protected from radiation by high levels of free radical scavengers even in the presence of oxygen. This led us to hypothesize that BCSCs exhibit an OER of 1. Using four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, SUM159PT) and primary breast cancer samples, we determined the number of BCSCs using cancer stem cell markers (ALDH1, low proteasome activity), compared radiation clonogenic survival and mammosphere formation under normoxic and hypoxic conditions, and correlated these results to the expression levels of key members of the free radical scavenging systems. The number of BCSCs increased with increased aggressiveness of the cancer. This correlated with increased radioresistance (SF8Gy), and decreasing OERs. When cultured as mammospheres, breast cancer cell lines and primary samples were highly radioresistant and not further protected by hypoxia (OER∼1)

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study

Purpose: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb–July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. Results: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32–81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7–8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months’ treatment duration; median of 4 mm [IQR − 20, 4]. In a small subset of patients ( n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month’s duration of BrET. Discussion: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials

Lipomodelling of the breast.

Abstract Abstract #4149 Background: Lipomodelling is the autologous transfer of fat to correct congenital and post-surgical deformities. Recent improvements in technique have provided the opportunity for a greater volume of fat transfer thus increasing its potential application following surgery for benign and malignant breast disease.&amp;#x2028; Materials &amp; methods: After injecting a solution of local anaesthetic, normal saline and 1:106 adrenaline into donor sites in the abdomen and thighs, fat was aspirated with 3mm cannulae and centrifuged for 5 minutes. The fat was then re-injected into pre-marked areas in the breast using a 3mm injection cannula. Patients were followed up in a specialist breast clinic.&amp;#x2028; Results: 23 patients (22 female, 1 male) were treated between November 2007 and May 2008. The mean age was 50.6 years (36-61).&amp;#x2028; &amp;#x2028; Prior to lipomodelling, volume deficit was observed in all patients. A visible depression was identified in 43.5% (n=10), significant flap atrophy in 21.7% (n=5), skin tethering in 21.7% (n=5) and implant rippling in 13% (n=3). Ten patients (43.5%) required lipomodelling to the upper pole, while in 7 patients (30.4%), the location was closely associated with the surgical scar.&amp;#x2028; The average volume of fat harvested was 210.7 ml (85-510), and that injected per breast was 107.1 ml (45-206). Injections were stopped when slight overfilling was observed. Excessive tissue tension was avoided. Operative time varied between 45-100 minutes.&amp;#x2028; During the first follow up visit, satisfactory results were recorded. 3 patients were booked for their second operation.&amp;#x2028; Nine patients were seen at 3-4 months (second follow up visit). Two patients had clinical and radiological evidence of fat necrosis. One patient had marked volume resorption and numbness at the donor site. Eight patients had good volume retention. Two patients were booked for further lipomodelling at this stage.&amp;#x2028; One patient had further lipomodelling five months after the first session, with satisfactory results, and is awaiting a third session.&amp;#x2028; &amp;#x2028; Discussion: Early results have shown satisfactory cosmetic outcome and patient satisfaction. The technical simplicity and autologous nature make lipomodelling an attractive option to both surgeon and patient. However it is not universally successful and further follow-up is required before the long term effects of the technique in cancer patients can be confirmed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4149.</jats:p