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Background: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk®) for the analysis of risk genes for familial breast and ovarian cancer. Summary: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. Key Messages: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures.
The microtubule (MT) cytoskeleton is crucial for cell motility and migration by regulating multiple cellular activities such as transport and endocytosis of key components of focal adhesions (FA). The kinesin-13 family is important in the regulation of MT dynamics and the best characterized member of this family is the mitotic centromere-associated kinesin (MCAK/KIF2C). Interestingly, its overexpression has been reported to be related to increased metastasis in various tumor entities. Moreover, MCAK is involved in the migration and invasion behavior of various cell types. However, the precise molecular mechanisms were not completely clarified. To address these issues, we generated CRISPR/dCas9 HeLa and retinal pigment epithelium (RPE) cell lines overexpressing or downregulating MCAK. Both up- or downregulation of MCAK led to reduced cell motility and poor migration in malignant as well as benign cells. Specifically, it’s up- or downregulation impaired FA protein composition and phosphorylation status, interfered with a proper spindle and chromosome segregation, disturbed the assembly and disassembly rate of FA, delayed cell adhesion, and compromised the plus-tip dynamics of MTs. In conclusion, our data suggest MCAK act as an important regulator for cell motility and migration by affecting the actin-MT cytoskeleton dynamics and the FA turnover, providing molecular mechanisms by which deregulated MCAK could promote malignant progression and metastasis of tumor cells.
Simple Summary: Early and accurate diagnosis of breast cancer that has spread to other organs and tissues is crucial, as therapeutic decisions and outcome expectations might change. Computed tomography (CT) is often used to detect breast cancer’s spread, but this method has its weaknesses. The computer-assisted technique “radiomics” extracts grey-level patterns, so-called radiomic features, from medical images, which may reflect underlying biological processes. Our retrospective study therefore evaluated whether breast cancer spread can be predicted by radiomic features derived from iodine maps, an application on a new generation of CT scanners visualizing tissue blood flow. Based on 77 patients with newly diagnosed breast cancer, we found that this approach might indeed predict cancer spread to other organs/tissues. In the future, radiomics may serve as an additional tool for cancer detection and risk assessment.
Abstract: Dual-energy CT (DECT) iodine maps enable quantification of iodine concentrations as a marker for tissue vascularization. We investigated whether iodine map radiomic features derived from staging DECT enable prediction of breast cancer metastatic status, and whether textural differ- ences exist between primary breast cancers and metastases. Seventy-seven treatment-naïve patients with biopsy-proven breast cancers were included retrospectively (41 non-metastatic, 36 metastatic). Radiomic features including first-, second-, and higher-order metrics as well as shape descriptors were extracted from volumes of interest on iodine maps. Following principal component analysis, a multilayer perceptron artificial neural network (MLP-NN) was used for classification (70% of cases for training, 30% validation). Histopathology served as reference standard. MLP-NN predicted metastatic status with AUCs of up to 0.94, and accuracies of up to 92.6 in the training and 82.6 in the validation datasets. The separation of primary tumor and metastatic tissue yielded AUCs of up to 0.87, with accuracies of up to 82.8 in the training, and 85.7 in the validation dataset. DECT iodine map-based radiomic signatures may therefore predict metastatic status in breast cancer patients. In addition, microstructural differences between primary and metastatic breast cancer tissue may be reflected by differences in DECT radiomic features.
Our aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR- BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.
Simple Summary: Currently, it is unclear which kind of axillary staging surgery breast cancer patients with lymph node metastasis should receive after neoadjuvant chemotherapy. For decades, these patients have been treated with a full axillary lymph node dissection, even if they converted to clinical node negativity. However, the removal of a large number of lymph nodes during the procedure can increase arm morbidity and impact quality of life. Therefore, several studies investigated less radical surgical strategies in this setting, such as sentinel lymph node biopsy or targeted axillary dissection, i.e., removal of a previously marked node combined with sentinel node removal. In this review, we summarize current evidence on the different surgical techniques and compare national and international recommendations. We show that many questions regarding oncological safety of different surgery types and the optimal marking technique remain unanswered and present the multinational prospective cohort study AXSANA that will address these open issues.
Abstract: In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).