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  • 1
    Online Resource
    Online Resource
    Resemblance of the Recurrence Patterns in Primary Systemic, Primary Surgery and Secondary Oncoplastic Surgery
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 11 ( 2022-11-17), p. 8874-8885
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 11 ( 2022-11-17), p. 8874-8885
    Abstract: Purpose: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer. Methods: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent. Results: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup. Conclusion: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …).
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29110698
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 2
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    FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 5 ( 2021-02-25), p. 956-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 5 ( 2021-02-25), p. 956-
    Abstract: Diagnosis in an advanced state is a major hallmark of ovarian cancer and recurrence after first line treatment is common. With upcoming novel therapies, tumor markers that support patient stratification are urgently needed to prevent ineffective therapy. Therefore, the transcription factor FOXM1 is a promising target in ovarian cancer as it is frequently overexpressed and associated with poor prognosis. In this study, fresh tissue specimens of 10 ovarian cancers were collected to investigate tissue cultures in their ability to predict individual treatment susceptibility and to identify the benefit of FOXM1 inhibition. FOXM1 inhibition was induced by thiostrepton (3 µM). Carboplatin (0.2, 2 and 20 µM) and olaparib (10 µM) were applied and tumor susceptibility was analyzed by tumor cell proliferation and apoptosis in immunofluorescence microscopy. Resistance mechanisms were investigated by determining the gene expression of FOXM1 and its targets BRCA1/2 and RAD51. Ovarian cancer tissue was successfully maintained for up to 14 days ex vivo, preserving morphological characteristics of the native specimen. Thiostrepton downregulated FOXM1 expression in tissue culture. Individual responses were observed after combined treatment with carboplatin or olaparib. Thus, we successfully implemented a complex tissue culture model to ovarian cancer and showed potential benefit of combined FOXM1 inhibition.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13050956
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 3
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    Online Resource
    The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 5 ( 2021-03-05), p. 1119-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 5 ( 2021-03-05), p. 1119-
    Abstract: Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13051119
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 4
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    Online Resource
    Targeted Sequencing of Plasma-Derived vs. Urinary cfDNA from Patients with Triple-Negative Breast Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 17 ( 2022-08-24), p. 4101-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 17 ( 2022-08-24), p. 4101-
    Abstract: In breast cancer, the genetic profiling of circulating cell-free DNA (cfDNA) from blood plasma was shown to have good potential for clinical use. In contrast, only a few studies were performed investigating urinary cfDNA. In this pilot study, we analyzed plasma-derived and matching urinary cfDNA samples obtained from 15 presurgical triple-negative breast cancer patients. We used a targeted next-generation sequencing approach to identify and compare genetic alterations in both body fluids. The cfDNA concentration was higher in urine compared to plasma, but there was no significant correlation between matched samples. Bioinformatical analysis revealed a total of 3339 somatic breast-cancer-related variants (VAF ≥ 3%), whereof 1222 vs. 2117 variants were found in plasma-derived vs. urinary cfDNA, respectively. Further, 431 shared variants were found in both body fluids. Throughout the cohort, the recovery rate of plasma-derived mutations in matching urinary cfDNA was 47% and even 63% for pathogenic variants only. The most frequently occurring pathogenic and likely pathogenic mutated genes were NF1, CHEK2, KMT2C and PTEN in both body fluids. Notably, a pathogenic CHEK2 (T519M) variant was found in all 30 samples. Taken together, our results indicated that body fluids appear to be valuable sources bearing complementary information regarding the genetic tumor profile.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14174101
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    The Importance of Clinical Examination under General Anesthesia: Improving Parametrial Assessment in Cervical Cancer Patients
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 12 ( 2021-06-13), p. 2961-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 12 ( 2021-06-13), p. 2961-
    Abstract: Background: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. Methods: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). Results: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar’s odds ratio [OR] = 2.0, 95%CI 1.25–3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p 〈 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p 〈 0.0001) compared to smaller tumors ( 〈 2.5 cm). Body mass index had no influence on performance of either method. Conclusions: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13122961
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 6
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    Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 19 ( 2021-09-29), p. 4884-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 19 ( 2021-09-29), p. 4884-
    Abstract: Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13194884
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    Heterogeneity between Core Needle Biopsy and Synchronous Axillary Lymph Node Metastases in Early Breast Cancer Patients—A Comparison of HER2, Estrogen and Progesterone Receptor Expression Profiles during Primary Treatment Regime
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 8 ( 2022-04-07), p. 1863-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 8 ( 2022-04-07), p. 1863-
    Abstract: In breast cancer therapeutic decisions are based on the expression of estrogen (ER), progesterone (PR), the human epidermal growth factor 2 (HER2) receptors and the proliferation marker Ki67. However, only little is known concerning heterogeneity between the primary tumor and axillary lymph node metastases (LNM) in the primary site. We retrospectively analyzed receptor profiles of 215 early breast cancer patients with axillary synchronous LNM. Of our cohort, 69% were therapy naive and did not receive neoadjuvant treatment. Using immunohistochemistry, receptor status and Ki67 were compared between core needle biopsy of the tumor (t-CNB) and axillary LNM obtained during surgery. The discordance rates between t-CNB and axillary LNM were 12% for HER2, 6% for ER and 20% for PR. Receptor discordance appears to already occur at the primary site. Receptor losses might play a role concerning overtreatment concomitant with adverse drug effects, while receptor gains might be an option for additional targeted or endocrine therapy. Hence, not only receptor profiles of the tumor tissue but also of the synchronous axillary LNM should be considered in the choice of treatment.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14081863
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
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    Online Resource
    Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-17), p. 568-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-17), p. 568-
    Abstract: Background: Patients with hormone-receptor-positive (HR+) breast cancer are at increased risk for late recurrence. One reason might be disseminated tumor cells (DTCs), which split off in the early stages of the disease and metastasize into the bone marrow (BM). Methods: We developed a novel multi-parameter immunofluorescence staining protocol using releasable and bleachable antibody–fluorochrome-conjugates. This sequential procedure enabled us to analyze six distinct phenotypical and therapy-related markers on the same DTC. We characterized BM aspirates from 29 patients with a HR+ tumor and a known positive DTC status—based on the standardized detection of epithelial cells in BM. Results: Using the immunofluorescence staining, a total of 153 DTCs were detected. Luminal A patients revealed a higher DTC count compared with luminal B. The majority of the detected DTCs were CK-positive (128/153). However, in 16 of 17 luminal A patients we found HER2-positive DTCs. We detected CK-negative DTCs (25/153) in 12 of 29 patients. Of those cells, 76% were Ki67-positive and 68% were HER2-positive. Moreover, we detected DTC clusters consisting of mixed characteristics in 6 of 29 patients. Conclusions: Using sequential multi-parameter imaging made it possible to identify distinct DTC profiles not solely based on epithelial features. Our findings indicate that characterization rather than quantification of DTCs might be relevant for treatment decisions.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030568
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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