Development of metastasis and survival prediction model of luminal and non-luminal breast cancer with weakly supervised learning based on pathomics.

Objective: Breast cancer stands as the most prevalent form of cancer among women globally. This heterogeneous disease exhibits varying clinical behaviors. The stratification of breast cancer patients into risk groups, determined by their metastasis and survival outcomes, is pivotal for tailoring personalized treatments and therapeutic interventions. The pathological sections of radical specimens encompass a diverse range of histological information pertinent to the metastasis and survival of patients. In this study, our objective is to develop a deep learning model utilizing pathological images to predict the metastasis and survival outcomes for breast cancer patients. Methods: This study utilized pathological sections from 204 radical mastectomy specimens obtained between January 2013 and December 2014 at the Second Affiliated Hospital of the Medical College of Zhejiang University. The 204 pathological slices were scanned and transformed into whole slide imaging (WSI), with manual labeling of all tumor areas. The WSI was then partitioned into smaller tiles measuring 512 × 512 pixels. Three networks, namely Densely Connected Convolutional Network 121 (DenseNet121), Residual Network (ResNet50), and Inception_v3, were assessed. Subsequently, we combined patch-level predictions, probability histograms, and Term Frequency-Inverse Document Frequency (TF-IDF) features to create comprehensive participants representations. These features served as the foundational input for developing a machine learning algorithm for metastasis analysis and a Cox regression model for survival analysis. Result: Our results show that the Inception_v3 model shows a particularly robust patch recognition ability for estrogen receptor (ER) recognition. Our pathological model shows high accuracy in predicting tumor regions. The train area under the curve (AUC) of the Inception_v3 model based on supervised learning is 0.975, which is higher than the model established by weakly supervised learning. But the AUC of the metastasis prediction in training and testing sets is higher than value based on supervised learning. Furthermore, the C-index of the survival prediction model is 0.710 in the testing sets, which is also better than the value by supervised learning. Conclusion: Our study demonstrates the significant potential of deep learning models in predicting breast cancer metastasis and prognosis, with the pathomic model showing high accuracy in identifying tumor areas and ER status. The integration of clinical features and pathomics signature into a nomogram further provides a valuable tool for clinicians to make individualized treatment decisions.