Abstract 5561: Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a non-obligatory precursor to invasive breast cancer (IBC). Currently there are no reliable markers to indicate if DCIS will progress IBC after an initial treatment, or if it will remain as DCIS. Because of this uncertainty, standard treatment for DCIS includes surgery with or without radiotherapy. Breast microcalcifications are a common feature in the mammographic detection of DCIS and occur in around 80% of DCIS and 50% of IBC. Despite this, their potential role in the development of DCIS and with progression to IBC remains largely unexplored. The main aim of the study is to identify novel biomarkers for DCIS prognosis, based on chemical and molecular compositional changes of calcifications and their surrounding soft tissue in DCIS. Methods: Consecutive tissue section from 422 patients were analyzed using mid-infrared and Raman hyperspectral imaging and X-ray diffraction (XRD) and included (i) ‘DCIS controls’ (DCIS without recurrence) (n=193), (ii) ‘DCIS cases’ (DCIS which subsequently recurred as an invasive disease) (n=123), (iii) ‘synchronous DCIS with invasive cancer’ (n=44) and ‘benign’ (n=62) groups. Both parametrized and data mining approaches including cluster analysis, unsupervised and supervised multivariate statistical analysis and biomodelling based on leave-one-sample-out cross-validation were used to classify the data and develop DCIS prediction models. Results: Prediction modelling of 314 calcification and soft tissue spectral images from 170 patients (‘DCIS controls’=118 versus ‘DCIS cases’=52) showed an AUROC mean value of 0.85 in distinguishing DCIS that did not recur from DCIS that recurred as IBC. Prediction modelling of XRD data from 124 patients (‘DCIS controls’=67 versus ‘DCIS cases’=57) showed an AUROC mean value of 0.80. The calcification spectral features showed pathology specific changes in phosphate to carbonate ratio as well as changes in magnesium whitlockite content. The epithelial features showed changes in protein secondary structure and content indicating structural remodeling between the two groups. XRD parametrized data analysis corroborated these observations in terms of difference in whitlockite, as well as crystallinity/unit axis of the measured calcifications. The prediction models are currently being tested independently on the remaining sample data. Conclusion: Complementary chemical and molecular analysis of breast calcifications and soft tissue using spectroscopy and XRD imaging predicts the likely progression of DCIS to IBC. Subject to the ongoing validation of biomarkers, these approaches appear as promising DCIS risk assessment tools that can inform diagnosis, prognosis and treatment options. Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Rachel Factor, Allison Hall, Sarah Pinder, Ihssane Bouybayoune, Elinor Sawyer, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Jelle Wesseling, Shelley Hwang, Keith Rogers, Nick Stone, Grand Challenge PRECISION consortium. Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5561.