RESUMO
The expression of human epidermal growth factor receptor 2 (HER2) protein or gene transcripts is critical for therapeutic decision making in breast cancer. We examined the performance of a digitalized and artificial intelligence (AI)-assisted workflow for HER2 status determination in accordance with the American Society of Clinical Oncology (ASCO)/College of Pathologists (CAP) guidelines. Our preliminary cohort consisted of 495 primary breast carcinomas, and our study cohort included 67 primary breast carcinomas and 30 metastatic deposits, which were evaluated for HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH). Three practicing breast pathologists independently assessed and scored slides, building the ground truth. Following a washout period, pathologists were provided with the results of the AI digital image analysis (DIA) and asked to reassess the slides. Both rounds of assessment from the pathologists were compared to the AI results and ground truth for each slide. We observed an overall HER2 positivity rate of 15% in our study cohort. Moderate agreement (Cohen's κ 0.59) was observed between the ground truth and AI on IHC, with most discrepancies occurring between 0 and 1+ scores. Inter-observer agreement amongst pathologists was substantial (Fleiss´ κ 0.77) and pathologists' agreement with AI scores was 80.6%. Substantial agreement of the AI with the ground truth (Cohen´s κ 0.80) was detected on ISH-stained slides, and the accuracy of AI was similar for the primary and metastatic tumors. We demonstrated the feasibility of a combined HER2 IHC and ISH AI workflow, with a Cohen's κ of 0.94 when assessed in accordance with the ASCO/CAP recommendations.
RESUMO
OBJECTIVE: This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies. METHODS: Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease. RESULTS: Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies. CONCLUSIONS: Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909.
