Tumour Stroma Ratio Assessment Using Digital Image Analysis Predicts Survival in Triple Negative and Luminal Breast Cancer

SIMPLE SUMMARY: Tumour stroma is known to predict outcome and play an important role in the growth and spread of solid tumours and their response to therapy. In breast cancer, there is evidence that the tumour stroma ratio (TSR) can predict outcome in aggressive triple negative breast cancer, but its value for the more common hormone receptor positive breast cancer is unclear. Using computerised image analysis and machine learning algorithms, we show that TSR is an important factor in predicting outcome for triple negative disease and hormone receptor positive cancer. However, its influence on good or poor outcome appears to depend on tumour type and the relative predominance of the stromal component. By better understanding the role of the tumour stroma in cancer growth, and its response to treatment, this study may help support the role of TSR as a new prognostic marker for breast cancer to guide clinical decision making. ABSTRACT: We aimed to determine the clinical significance of tumour stroma ratio (TSR) in luminal and triple negative breast cancer (TNBC) using digital image analysis and machine learning algorithms. Automated image analysis using QuPath software was applied to a cohort of 647 breast cancer patients (403 luminal and 244 TNBC) using digital H&E images of tissue microarrays (TMAs). Kaplan–Meier and Cox proportional hazards were used to ascertain relationships with overall survival (OS) and breast cancer specific survival (BCSS). For TNBC, low TSR (high stroma) was associated with poor prognosis for both OS (HR 1.9, CI 1.1–3.3, p = 0.021) and BCSS (HR 2.6, HR 1.3–5.4, p = 0.007) in multivariate models, independent of age, size, grade, sTILs, lymph nodal status and chemotherapy. However, for luminal tumours, low TSR (high stroma) was associated with a favourable prognosis in MVA for OS (HR 0.6, CI 0.4–0.8, p = 0.001) but not for BCSS. TSR is a prognostic factor of most significance in TNBC, but also in luminal breast cancer, and can be reliably assessed using quantitative image analysis of TMAs. Further investigation into the contribution of tumour subtype stromal phenotype may further refine these findings.