Project 14 – Analysis of circulating biomarkers for minimally invasive early detection of Breast Cancer (BC)

Hypothesis: BC screening programs allow early disease detection, but they have drawbacks. Appropriate risk stratification would lead to personalized screening programs tailored on individual risk.

Background and Significance: Although mammography has become standard of care in BC screening, its limitations are well recognized (overdiagnosis, the use of ionizing radiation, poor accuracy in women with dense breast tissue, a relatively high rate of false positives, and personal discomfort). In addition, the current screening protocols are based on woman’s age only, ignoring other risk factors and defining a single screening periodicity within pre-specified age ranges. Circulating biomarkers analysis and SNP assessment together with evaluation of modifiable risk factors, breast density and well known factors, could help in a better definition of individual BC risk.

Objectives: to provide comprehensive training on BC prevention to ESR14 who will work inside a private no-profit foundation that manages several primary and secondary prevention programs, especially for BC. In particular, ESR14 will be involved in the Andromeda project to tailor BC screening according to life-styles and genetic risk and will be trained on the analysis of circulating-free microRNAs (cf-miRNA) to detect BC or predict BC risk as well as on the evaluation of polygenic risk score from multiple SNPs assessment.

The mathematical part of this project will deal with modeling breast cancer risk using molecular variables (from DNA or circulating RNA) and non molecular ones. Multivariable penalized (elastic-net, lasso) logistic regression, imposing or not shrinkage on the non-molecular predictors. But also methodologes to cluster samples based on molecular and non molecular features or machine learning techniques to predict the presence of disease.

The student will spend 7 months at the Ecole Polytecnique Federale of Lausanne to measure sex hormones and work with the team of Dr Kathrin Brisken (coordinator of the program) and 6 months at the University of Helsinki to study the influence of environment and life-styles on breast cancer risk, in the team of Dr Yaakko Kaprio.

Related readings

Giordano, L. et al. The ANDROMEDA prospective cohort study: predictive value of combined criteria to tailor breast cancer screening and new opportunities from circulating markers: study protocol. BMC Cancer 17, 785, 5 (2017).

Mavaddat, N. et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet 104, 21-34, (2019),

Hamam, R. et al. Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis 8, e3045 (2017).

Mello-Grand, M. et al. Circulating microRNAs combined with PSA for accurate and non-invasive prostate cancer detection. Carcinogenesis (2018).