Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas

Altitudinally restricted communities of Schizophoran flies in Queensland's Wet Tropics: vulnerability to climate change

The Australian Wet Tropics World Heritage Area (WTWHA) contains a number of highland vertebrates predicted to face extinction due to a warming climate, but little is known about risks to invertebrates, which are vital to ecosystem health. This study investigates the distribution and abundance patterns of the Dipteran sub-order Schizophora along an altitudinal transect in the Carbine Uplands of the WTWHA using Malaise traps. The season of peak abundance changed with altitude, with highland abundance peaking in October, and lowland abundance peaking in April. There was a high level of species turnover with altitude, and some evidence for distinct low-, mid-, and high-elevation assemblages, with the high-elevation assemblage containing the most restricted species. We would expect this high-elevation assemblage to be at risk of local extinction with 2–3° of warming, and the mid-elevation assemblage to be at risk with 4–5° warming. Future work should continue sampling to confirm patterns presented here and to monitor range shifts with climate change. A highland species - Helosciomyza ferruginea Hendel is suggested as a good indicator species for such monitoring

The clonal and mutational evolution spectrum of primary triple-negative breast cancers

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. © 2012 Macmillan Publishers Limited. All rights reserved