HER2 (human epidermal growth factor receptor 2) is a protein that is found on the surface of some cells, including breast cells. HER2 plays a role in cell growth, division, and repair, and when it is overexpressed, it can contribute to the development of certain types of cancer, particularly breast cancer. HER2 overexpression occurs in approximately 20\% of cases, and it is associated with more aggressive tumor phenotypes and poorer prognosis. This makes its status an important factor in determining treatment options for breast cancer. While HER2 expression is typically diagnosed through a combination of immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) testing on breast cancer tissue samples, we sought to determine to what extent it is possible to diagnose from H\&E-stained specimens. To this effect we trained a deep learning model to classify HER2-positive image patches using a dataset of 10 whole-slide images (5 HER2-positive, 5 HER2-negative). We evaluated the model on a different test set consisting of patches extracted from 10 WSIs (5 HER2-positive, 5 HER2-negative), and we compared the performance against two pathologists on 100 512x512 patches (50 HER2-positive, 50 HER2-negative). Overall, the model achieved an accuracy of 73\% while the pathologists achieved 58\% and 47\%, respectively.

M.T. and F.K. are employees of Medmain Inc.

This study is based on results obtained from a project, JPNP14012, subsidized by the New Energy and Industrial Technology Development Organization (NEDO).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The experimental protocol was approved by the ethical board of Kamachi Group Hospitals (Wajiro and Shinkomonji hospitals, Fukuoka, Japan) (No. 173). All research activities complied with all relevant ethical regulations and were performed in accordance with relevant guidelines and regulations in the all hospitals mentioned above (Wajiro and Shinkomonji hospitals, Fukuoka, Japan). Informed consent to use histopathological samples and pathological diagnostic reports for research purposes had previously been obtained from all patients prior to the surgical procedures at all hospitals, and the opportunity for refusal to participate in research had been guaranteed by an opt-out manner.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Due to specific institutional requirements governing privacy protection, datasets used in this study are not publicly available.