Early breast cancer risk detection: a novel framework leveraging polygenic risk scores and machine learning

Breast cancer (BC) is the most common cancer and the second leading cause of cancer death in women; an estimated one in eight women in the USA will develop BC during her lifetime. However, current methods of BC screening, including clinical breast exams, mammograms, biopsies and others, are often underused due to limited access, expense and a lack of risk awareness, causing 30% (up to 80% in low-income and middle-income countries) of patients with BC to miss the precious early detection phase.

This study creates a key step to supplement the current BC diagnostic pipeline: a prescreening platform, prior to traditional detection and diagnostic steps. We have developed BREast CAncer Risk Detection Application (BRECARDA), a novel framework that personalises BC risk assessment using artificial intelligence neural networks to incorporate relevant genetic and non-genetic risk factors. A polygenic risk score (PRS) was enhanced by employing AnnoPred and validated by fivefolds cross-validation, outperforming three existing state-of-the-art PRS methods.

We used data from 97 597 female participants of the UK BioBank to train our algorithm. Using the enhanced PRS thus trained together with non-genetic information, BRECARDA was evaluated in a testing dataset with 48 074 UK Biobank female participants and achieved a high accuracy of 94.28% and area under the curve of 0.7861. Our optimised AnnoPred outperformed other state-of-the-art methods on quantifying genetic risk, indicating its potential for supplementing the current BC detection tests, population screening and risk evaluation.

BRECARDA can enhance disease risk prediction, identify high-risk individuals for BC screening, facilitate disease diagnosis and improve population-level screening efficiency. It can serve as a valuable and supplemental platform to assist doctors in BC diagnosis and evaluation.