Breast cancer, the most common malignancy among women, requires precise detection and classification for effective treatment. Immunohistochemistry (IHC) biomarkers like HER2, ER, and PR are critical for identifying breast cancer subtypes. However, traditional IHC classification relies on pathologists' expertise, making it labor-intensive and subject to significant inter-observer variability. To address these challenges, this study introduces the India Pathology Breast Cancer Dataset (IPD-Breast), comprising of 1,272 IHC slides (HER2, ER, and PR) aimed at automating receptor status classification. The primary focus is on developing predictive models for HER2 3-way classification (0, Low, High) to enhance prognosis. Evaluation of multiple deep learning models revealed that an end-to-end ConvNeXt network utilizing low-resolution IHC images achieved an AUC, F1, and accuracy of 91.79%, 83.52%, and 83.56%, respectively, for 3-way classification, outperforming patch-based methods by over 5.35% in F1 score. This study highlights the potential of simple yet effective deep learning techniques to significantly improve accuracy and reproducibility in breast cancer classification, supporting their integration into clinical workflows for better patient outcomes.

Classifying breast cancer molecular subtypes is crucial for tailoring treatment strategies. While immunohistochemistry (IHC) and gene expression profiling are standard methods for molecular subtyping, IHC can be subjective, and gene profiling is costly and not widely accessible in many regions. Previous approaches have highlighted the potential application of deep learning models on H&E-stained whole slide images (WSI) for molecular subtyping, but these efforts vary in their methods, datasets, and reported performance. In this work, we investigated whether H&E-stained WSIs could be solely leveraged to predict breast cancer molecular subtypes (luminal A, B, HER2-enriched, and Basal). We used 1,433 WSIs of breast cancer in a two-step pipeline: first, classifying tumor and non-tumor tiles to use only the tumor regions for molecular subtyping; and second, employing a One-vs-Rest (OvR) strategy to train four binary OvR classifiers and aggregating their results using an eXtreme Gradient Boosting (XGBoost) model. The pipeline was tested on 221 hold-out WSIs, achieving an overall macro F1 score of 0.95 for tumor detection and 0.73 for molecular subtyping. Our findings suggest that, with further validation, supervised deep learning models could serve as supportive tools for molecular subtyping in breast cancer. Our codes are made available to facilitate ongoing research and development.

Immunohistochemistry (IHC) analysis is a well-accepted and widely used method for molecular subtyping, a procedure for prognosis and targeted therapy of breast carcinoma, the most common type of tumor affecting women. There are four molecular biomarkers namely progesterone receptor (PR), estrogen receptor (ER), antigen Ki67, and human epidermal growth factor receptor 2 (HER2) whose assessment is needed under IHC procedure to decide prognosis as well as predictors of response to therapy. However, IHC scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility, high subjectivity, and often incorrect scoring in low-score cases. In this paper, we present, a deep learning-based semi-supervised trained, fully automatic, decision support system (DSS) for IHC scoring of invasive ductal carcinoma. Our system automatically detects the tumor region removing artifacts and scores based on Allred standard. The system is developed using 3 million pathologist-annotated image patches from 300 slides, fifty thousand in-house cell annotations, and forty thousand pixels marking of HER2 membrane. We have conducted multicentric trials at four centers with three different types of digital scanners in terms of percentage agreement with doctors. And achieved agreements of 95, 92, 88 and 82 percent for Ki67, HER2, ER, and PR stain categories, respectively. In addition to overall accuracy, we found that there is 5 percent of cases where pathologist have changed their score in favor of algorithm score while reviewing with detailed algorithmic analysis. Our approach could improve the accuracy of IHC scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. Our system is highly modular. The proposed algorithm modules can be used to develop DSS for other cancer types.

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

Breast cancer is the most common cancer among women worldwide. The human epidermal growth factor receptor 2(HER2) with immunohistochemical(IHC) is widely used for pathological evaluation to provide the appropriate therapy for patients with breast cancer. However, the deficiency of pathologists is extremely significant in the current society, and visual diagnosis of the HER2 overexpression is subjective and susceptible to inter-observer variation. Recently, with the rapid development of artificial intelligence(AI) in disease diagnosis, several automated HER2 scoring methods using traditional computer vision or machine learning methods indicate the improvement of the HER2 diagnostic accuracy, but the unreasonable interpretation in pathology, as well as the expensive and ethical issues for annotation, make these methods still have a long way to deploy in hospitals to ease pathologists' burden in real. In this paper, we propose a HER2 automated scoring system that strictly follows the HER2 scoring guidelines simulating the real workflow of HER2 scores diagnosis by pathologists. Unlike the previous work, our method takes the positive control of HER2 into account to make sure the assay performance for each slide, eliminating work for repeated comparison and checking for the current field of view(FOV) and positive control FOV, especially for the borderline cases. Besides, for each selected FOV under the microscope, our system provides real-time HER2 scores analysis and visualizations of the membrane staining intensity and completeness corresponding with the cell classification. Our rigorous workflow along with the flexible interactive adjustion in demand substantially assists pathologists to finish the HER2 diagnosis faster and improves the robustness and accuracy. The proposed system will be embedded in our Thorough Eye platform for deployment in hospitals.

Predicting response to neoadjuvant therapy is a vexing challenge in breast cancer. In this study, we evaluate the ability of deep learning to predict response to HER2-targeted neo-adjuvant chemotherapy (NAC) from pre-treatment dynamic contrast-enhanced (DCE) MRI acquired prior to treatment. In a retrospective study encompassing DCE-MRI data from a total of 157 HER2+ breast cancer patients from 5 institutions, we developed and validated a deep learning approach for predicting pathological complete response (pCR) to HER2-targeted NAC prior to treatment. 100 patients who received HER2-targeted neoadjuvant chemotherapy at a single institution were used to train (n=85) and tune (n=15) a convolutional neural network (CNN) to predict pCR. A multi-input CNN leveraging both pre-contrast and late post-contrast DCE-MRI acquisitions was identified to achieve optimal response prediction within the validation set (AUC=0.93). This model was then tested on two independent testing cohorts with pre-treatment DCE-MRI data. It achieved strong performance in a 28 patient testing set from a second institution (AUC=0.85, 95% CI 0.67-1.0, p=.0008) and a 29 patient multicenter trial including data from 3 additional institutions (AUC=0.77, 95% CI 0.58-0.97, p=0.006). Deep learning-based response prediction model was found to exceed a multivariable model incorporating predictive clinical variables (AUC < .65 in testing cohorts) and a model of semi-quantitative DCE-MRI pharmacokinetic measurements (AUC < .60 in testing cohorts). The results presented in this work across multiple sites suggest that with further validation deep learning could provide an effective and reliable tool to guide targeted therapy in breast cancer, thus reducing overtreatment among HER2+ patients.