New breast cancer cases have surpassed lung cancer, becoming the world's most prevalent cancer. Despite advancing medical image analysis, deep learning's lack of interpretability limits its adoption among pathologists. Hence, a nuclei-level prior knowledge constrained multiple instance learning (MIL) (NPKC-MIL) for breast whole slide image (WSI) classification is proposed. NPKC-MIL primarily involves the following steps: Initially, employing the transfer learning to extract patch-level features and aggregate them into slide-level features through attention pooling. Subsequently, abstract the extracted nuclei as nodes, establish nucleus topology using the K-NN (K-Nearest Neighbors, K-NN) algorithm, and create handcrafted features for nodes. Finally, combine patch-level deep learning features with nuclei-level handcrafted features to fine-tune classification results generated by slide-level deep learning features. The experimental results demonstrate that NPKC-MIL outperforms current comparable deep learning models. NPKC-MIL expands the analytical dimension of WSI classification tasks and integrates prior knowledge into deep learning models to improve interpretability.