Silent theatre 1 – Sunday 3 November

3:50 pm-4:15 pm

Room: Hall 4


Programme session type(s): Silent theatre

Body composition and chemotherapy toxicity in women with early breast cancer: The Cando-3 study
Speaker: Ramsey Cutress
Affiliation: Faculty of Medicine, University of Southampton

Abstract:

Chemotherapy dosing is traditionally based on body surface area but there are additional challenges in  overweight and obese patients. The extent to which variations in the proportions of body Fat Mass (FM) and Fat Free Mass (FFM) at the outset of treatment influence the risk of chemotoxicity needs to be determined. Bioelectrical Impedance analysis can be used to measure body composition and other impedance values at routine clinic appointments for women receiving standard neo/adjuvant chemotherapy for early breast cancer.

 Hypothesis: Differences in impedance measures of resistance, reactance and phase angle, and/or derived estimates of elevated FM index and low FFM index can be individually and/or jointly predictive of chemotherapy toxicity. Primary Objective: To determine if higher FMi is associated with increased grade 3 chemotherapy toxicity in women receiving neo/adjuvant chemotherapy for early breast cancer Secondary objectives: To determine whether EBC patients with different body composition patterns receive intended chemotherapy dose intensity; to determine the relationship between sBIA-measured physical properties e.g. phase angle and reactance and grade 3 or higher chemotherapy toxicity.

 

Method

This WCRF-funded, observational cohort study will recruit 300 women (aged >18-<80) diagnosed with EBC, undergoing standard neo/adjuvant chemotherapy over a period of 18 months, across seven UK hospital centres. Phase-adjusted sBIA using the Seca 515 mBCA will be performed prior to each chemotherapy cycle and at 3-weeks and 3-months post final cycle. Chemotherapy related toxicities for each treatment will be recorded using the standard Common Terminology Criteria for Adverse Events (v5.0). All chemotherapy doses prescribed will be captured, including any dose delays or reductions; intended and delivered chemotherapy dose density will be calculated.   Primary analyses in this study will investigate whether measures of sBIA or body composition relate to chemotherapy toxicity and/ or reduced delivered chemotherapy dose intensity, and how these variables change during chemotherapy treatment.

Results

Conclusion

International Trends in Oesophageal Cancer Survival by Histological Subtype: A population-based study from seven high-income countries 1995-2014
Speaker: Eileen Morgan
Affiliation: International Agency for Research on Cancer

Abstract:

Survival from oesophageal cancer remains poor, even across high-income countries. In view of the changing landscape of risk factors and incidence of the two main subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC), it is important to assess survival by histology over time and across countries.

Method

In the ICBP SURVMARK-2 project, data on new cases of oesophageal cancer were provided by cancer registries from 21 jurisdictions covering seven high-income countries for the period 1995-2014 (followed up until 31st December 2015). 1- and 3-year age-standardised net survival estimates alongside incidence rates were calculated for AC and SCC by sex, age group and period of diagnosis for each country.

Results

There were 111,444 cases of AC and 73,085 cases of SCC diagnosed during 1995-2014 across the seven countries, with AC emerging as the most common subtype with incidence rates up to 7.8 per 100,000 in 2014. Improvements in 1- and 3-year survival from both AC and SCC were observed, with notable improvements made for AC as well as among younger age groups (<65 years) and at 1-year after diagnosis for both subtypes. Survival was consistently higher for both subtypes in Australia and Ireland followed by Norway, Denmark, New Zealand, the UK and Canada. In patients diagnosed during 2010-2014, survival was higher for AC compared to SCC with 1-year net survival ranging from 46.9% (Canada) to 54.4% (Ireland) for AC and from 39.6% (Denmark) to 54.1% (Australia) for SCC.

Conclusion

The improvements in survival observed across countries in oesophageal AC and SCC are likely an indication of advances in treatment. Survival remains low, with less marked improvements at 3-year follow-up, in older age groups and in patients with SCC, highlighting the need for further advances in early detection and treatment alongside primary prevention to reduce the overall burden from oesophageal cancer.

Activation of HER2-ELF3-KRAS axis specifically deteriorates KRASG13D mutant colorectal cancer
Speaker: Soo-Yeon Hwang
Affiliation: Ewha Womans University

Abstract:

Colorectal cancer (CRC) is generally characterized by accumulation of diverse genetic alterations. KRAS mutations are most importantly considered driving factors for CRC tumorigenesis. Unlike prior reports, many recent studies have begun to demonstrate isotype-dependent functional impacts of each KRAS variant. Particularly, KRASG13D has been described to exhibit unique features; some KRASG13D CRC patients exhibit worse prognosis but can also clinically benefit from anti-EGFR agents. Our study focused on clarifying HER2 as the key determinant of this phenomenon and establishing KRASG13D -selective inhibitory strategy.

Method

To assess the clinical significance of targeting HER2 in KRASG13D CRCs, we intensively analyzed public databases and grade III CRC patient samples. We additionally prepared HER2-silenced and -overexpressed CRC cells and applied various in vitro, in vivo assays for further evaluation.

Results

HER2 overexpression was directly associated with the poor prognosis of KRASG13D CRC patients by significantly promoting the EMT process. It also exhibited negative correlation with the cetuximab-sensitivity of KRASG13D CRCs. However, targeting the already overexpressed HER2 protein using trastuzumab was ineffective against KRASG13D CRC cell, while HER2 gene silencing induced favorable changes in their tumorigenic features and ameliorated the susceptibility to cetuximab. We newly found a transcriptional regulatory network of HER2-ELF3-KRAS, where ELF3 serves as a common transcription factor for both HER2 and KRAS. Thus, we identified a novel small molecule, BTCP, which downregulates HER2 at the transcriptional level by specifically interrupting ELF3-MED23 interaction. BTCP suppressed the gene expression of HER2, ELF3, and KRAS, inducing marked attenuation of total HER signaling in vitro and in vivo, eventually leading to a significant tumor regression.

Conclusion

Our findings demonstrate therapeutic relevance of regulating HER2 gene transcription as a critical strategy to overcome clinicopathological issues underlying KRASG13D CRCs. This may provide a valuable insight to the treatment landscape of KRAS mutant CRCs.