Search

BackgroundIn hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families. ObjectiveThe aims of this study are to develop the K-CASCADE (Korean–Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework. MethodsThe digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers. ResultsFunding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023. ConclusionsThis study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes. Trial RegistrationClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/ International Registered Report Identifier (IRRID)PRR1-10.2196/26264

Objective: Recent trends involving increased screening have led to broad populations being diagnosed with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS); as a result, many patients have had to receive surgery followed by standard treatment for ADH or DCIS. The common interest in reducing the use of superfluous invasive treatment has led us to question the necessity of surgical treatment for ADH or DCIS patients in a retrospective review. This work is expected to be a particularly useful reference as there have yet to be any studies describing the outcomes of initial treatment with tamoxifen without curative surgery in Korea. Methods: The clinicopathological characteristics and oncologic outcomes of 36 patients with DCIS or ADH diagnosis who received initial treatment with tamoxifen between 2013 and 2019 were investigated. Results: Among 36 patients enrolled, 30 were diagnosed with DCIS and six were diagnosed with ADH. The median age in the included cohort was 47 years old (range, 26–81 years). There was a change in the follow‐up strategy including the need for surgery in 13.9% of cases. The median time to surgery in those patients was 32 months (IQR, 17.5–63.5 months). Only one patient had upgraded to a higher nuclear grade, which was a case of ADH upgrading to intermediate DCIS. Three (8.3%) of 36 patients were upstaged to an invasive disease. Of them, two patients were upstaged to microinvasive ductal carcinoma, whereas one patient was diagnosed with metastatic invasive ductal carcinoma. Conclusion: The use of endocrine therapy without surgery could be a potential treatment strategy in patients with DCIS or ADH. Further validation in larger cohorts and in the context of clinical trials is needed. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion There is a clinical need to omit axillary lymph node dissection (ALND) when residual disease in sentinel lymph nodes (SLNs) is low after neoadjuvant chemotherapy (NAC). This study aimed to clarify the relationship between micrometastasis in SLNs after NAC and additional non‐SLN metastases by analyzing SLN biopsy results followed by ALND.This retrospective study reviewed clinical records of patients who underwent breast cancer surgery between January 2010 and June 2022 after NAC at Samsung Medical Center. Of 3944 patients, 806 underwent SLN biopsy followed by ALND. Intraoperative frozen SLN biopsy results were examined, including the number and size of metastases in SLNs, and further investigated the number of additional non‐SLN metastases.Among the 806 patients, 95 (11.8%) had micrometastasis on SLNs in frozen sections, of which 89 (93.7%) had clinically node‐positive (cN1‐3) breast cancer before NAC. Twenty‐three patients (24.2%) exhibited positive additional non‐SLNs after ALND. The presence of lymphovascular invasion (vs. absence; odds ratio [OR] = 4.02, p = .0151) and having two or more SLNs with micrometastasis (vs. a positive SLN; OR = 3.65, p = .0301) were significantly associated with additional non‐SLN metastases. Tumor subtypes and breast pathological complete response after NAC showed no correlation with the additional non‐SLN metastases.The study identified a 24.2% possibility of additional non‐SLN metastasis if micrometastases was detected in the SLN after NAC. This rate is significant, indicating that ALND cannot be omitted if low volume residual disease, such as micrometastasis, is identified in the SLN after NAC. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is a challenging form of breast cancer known for its aggressive nature and limited treatment options. The DESTINY-Breast 04 trial has demonstrated improved survival outcomes in metastatic human epithelial growth factor receptor 2 (HER2)-low breast cancer patients treated with trastuzumab-deruxtecan (T-Dxd). Since the potential proportion of breast cancer patients that may benefit from these novel agents are reported to be around 39% to 79%, investigating the role of HER2-low has been a topic of interest. By analyzing the outcomes of over 2500 patients, we discovered that those with HER2-low TNBC typically experience better survival rates than HER2-0 TNBC. This difference was especially significant in postmenopausal women. These findings suggest a potential re-evaluation of how TNBC is classified and treated, highlighting the importance of identifying HER2-low expression for improving personalized treatment strategies and patient care. TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed. [ABSTRACT FROM AUTHOR]