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1.
Cancers (Basel) ; 16(20)2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39456610

RESUMO

Background: Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. Methods: TNBC tissue sections from normal-weight (BMI<25) and overweight/obese patients (BMI≥25) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score. Results: Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI<25: 2.80 vs. BMI≥25: 10.45; p = 0.011) and lower numbers of CD31+ (BMI<25: 4.20 vs. BMI≥25: 2.40; p = 0.018) and CD34+ (BMI<25: 14.60 vs. BMI≥25: 5.20; p = 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI<25: 7.60 vs. BMI≥25: 25.39 in total; p = 0.001). Moreover, expression of CD36 (BMI<25: 2.15 vs. BMI≥25: 2.60; p = 0.041) and ANGPTL4 (BMI<25: 6.00 vs. BMI≥25: 9.80; p = 0.026) was elevated in the TNBC cells of overweight/obese patients. Conclusions: Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment.

2.
Mol Oncol ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367702

RESUMO

While cell-free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell-based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC-derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing. Results were linked to molecular features of primary tumors, metastases, and CTCs; CTC enumeration was linked to disease progression. Of 52 samples with positive CTC counts (≥1) from eight different cancer types, only CTCs from two salivary gland cancer (SGC) patients formed tumoroid cultures (P = 0.0005). Longitudinal CTC enumeration of one SGC patient closely reflected disease progression during treatment and revealed metastatic relapse earlier than clinical imaging. Multiomics analysis and functional in vitro drug testing identified potential resistance mechanisms and drug vulnerabilities. We conclude that cLB might add a functional dimension (to the genetic approaches) in the personalized management of rare, difficult-to-treat cancers such as SGC.

3.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39000582

RESUMO

The impact of the HER4 receptor on the growth and treatment of estrogen receptor-positive breast cancer is widely uncertain. Using CRISPR/Cas9 technology, we generated stable HER4 knockout variants derived from the HER4-positive MCF-7, T-47D, and ZR-75-1 breast cancer cell lines. We investigated tumor cell proliferation as well as the cellular and molecular mechanisms of tamoxifen, abemaciclib, AMG232, and NRG1 treatments as a function of HER4 in vitro. HER4 differentially affects the cellular response to tamoxifen and abemaciclib treatment. Most conspicuous is the increased sensitivity of MCF-7 in vitro upon HER4 knockout and the inhibition of cell proliferation by NRG1. Additionally, we assessed tumor growth and immunological effects as responses to tamoxifen and abemaciclib therapy in humanized tumor mice (HTM) based on MCF-7 HER4-wildtype and the corresponding HER4-knockout cells. Without any treatment, the enhanced MCF-7 tumor growth in HTM upon HER4 knockout suggests a tumor-suppressive effect of HER4 under preclinical but human-like conditions. This phenomenon is associated with an increased HER2 expression in MCF-7 in vivo. Independent of HER4, abemaciclib and tamoxifen treatment considerably inhibited tumor growth in these mice. However, abemaciclib-treated hormone receptor-positive breast cancer patients with tumor-associated mdm2 gene copy gains or pronounced HER4 expression showed a reduced event-free survival. Evidently, the presence of HER4 affects the efficacy of tamoxifen and abemaciclib treatment in different estrogen receptor-positive breast cancer cells, even to different extents, and is associated with unfavorable outcomes in abemaciclib-treated patients.


Assuntos
Aminopiridinas , Benzimidazóis , Neoplasias da Mama , Proliferação de Células , Receptor ErbB-4 , Tamoxifeno , Animais , Humanos , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Células MCF-7 , Receptor ErbB-4/metabolismo , Receptor ErbB-4/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética
4.
Front Oncol ; 14: 1354377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699636

RESUMO

Introduction: The negative impact of unmanaged psychological distress on quality of life and outcome in breast cancer survivors has been demonstrated. Fortunately, studies indicate that distress can effectively be addressed and even prevented using evidence-based interventions. In Germany prescription-based mobile health apps, known as DiGAs (digital health applications), that are fully reimbursed by health insurances, were introduced in 2020. In this study, the effectiveness of an approved breast cancer DiGA was investigated: The personalized coaching app PINK! Coach supports and accompanies breast cancer patients during therapy and follow-up. Methods: PINK! Coach was specifically designed for breast cancer (BC) patients from the day of diagnosis to the time of Follow-up (aftercare). The app offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT (DRKS00028699) was performed with n = 434 patients recruited in 7 German breast cancer centers from September 2022 until January 2023. Patients with BC were included independent of their stage of diseases, type of therapy and molecular characteristics of the tumor. Patients were randomized into one of two groups: The intervention group got access to PINK! over 12 weeks; the control group served as a waiting-list comparison to "standard of care." The primary endpoint was psychological distress objectified by means of Patient Health Questionnaire-9 (PHQ-9). Subgroups were defined to investigate the app's effect on several patient groups such as MBC vs. EBC patients, patients on therapy vs. in aftercare, patients who received a chemotherapy vs. patients who did not. Results: Efficacy analysis of the primary endpoint revealed a significant reduction in psychological distress (least squares estimate -1.62, 95% confidence interval [1.03; 2.21]; p<0.001) among intervention group patients from baseline to T3 vs, control group. Subgroup analysis also suggested improvements across all clinical situations. Conclusion: Patients with breast cancer suffer from psychological problems including anxiety and depression during and after therapy. Personalized, supportive care with the app PINK! Coach turned out as a promising opportunity to significantly improve psychological distress in a convenient, accessible, and low-threshold manner for breast cancer patients independent of their stage of disease (EBC/MBC), therapy phase (aftercare or therapy) or therapy itself (chemotherapy/other therapy options). The app is routinely available in Germany as a DiGA. Clinical Trial Registration: DRKS Trial Registry (DRKS00028699).

5.
Front Immunol ; 15: 1355130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742103

RESUMO

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Breast Cancer Res Treat ; 204(3): 607-615, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38238552

RESUMO

PURPOSE: The optimal time to initiation of adjuvant chemotherapy (TTAC) for triple negative breast cancer (TNBC) patients is unclear. This study evaluates the association between TTAC and survival in TNBC patients. METHODS: We conducted a retrospective study using data from a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018, registered in the Tumor Centre Regensburg was conducted. Data included demographics, pathology, treatment, recurrence and survival. TTAC was defined as days from primary surgery to first dose of adjuvant chemotherapy. The Kaplan-Meier method was used to evaluate impact of TTAC on overall survival (OS) and 5-year OS. RESULTS: A total of 245 TNBC patients treated with adjuvant chemotherapy and valid TTAC data were included. Median TTAC was 29 days. The group receiving systemic therapy within 22 to 28 days after surgery had the most favorable outcome, with median OS of 10.2 years. Groups receiving systemic therapy between 29-35 days, 36-42 days, and more than 6 weeks after surgery had significantly decreased median survival, with median OS of 8.3 years, 7.8 years, and 6.9 years, respectively. Patients receiving therapy between 22-28 days had significantly better survival compared to those receiving therapy between 29-35 days (p = 0.043), and patients receiving therapy after 22-28 days also demonstrated significantly better survival compared to those receiving therapy after more than 43 days (p = 0.033). CONCLUSION: Timing of adjuvant systemic therapy can influence OS in TNBC patients. Efforts should be made to avoid unnecessary delays in administering chemotherapy to ensure timely initiation of systemic therapy and optimize patient outcomes.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Estudos Retrospectivos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Terapia Combinada , Estadiamento de Neoplasias
7.
Breast Cancer Res Treat ; 202(3): 497-504, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37684426

RESUMO

PURPOSE: Currently, various techniques are available to mark and selectively remove initially suspicious axillary lymph nodes (target lymph nodes, TLNs) in breast cancer patients receiving neoadjuvant chemotherapy (NACT). To date, limited data are available on whether the use of magnetic seeds (MS) is suitable for localizing TLNs. This study aimed to investigate the feasibility of MS in patients undergoing target lymph node biopsy (TLNB) or targeted axillary dissection (TAD) after NACT. METHODS: Prospective data from the ongoing multicentric AXSANA study were extracted from selected patients in whom the TLN had been marked with an MS before NACT and who were enrolled from June 2020 to June 2023. The endpoints of the analysis were the detection rate, the rate of lost markers, and the potential impairment on magnetic resonance imaging (MRI) assessment. RESULTS: In 187 patients from 27 study sites in seven countries, MS were placed into the TLN before NACT. In 151 of these, post-NACT surgery had been completed at the time of analysis. In 146 patients (96.0%), a TLN could successfully be detected. In three patients, the seed was removed but no lymphoid tissue was detected on histopathology. The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. CONCLUSION: MS show excellent applicability for TLNB/TAD when inserted before NACT with a high DR and a low rate of lost markers. Axillary MS can impair MRI assessment of the breast. TRIAL REGISTRATION NUMBER: NCT04373655 (date of registration May 4, 2020).

8.
J Cancer Res Clin Oncol ; 149(13): 11941-11950, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37418056

RESUMO

PURPOSE: For patients with triple negative breast cancer (TNBC), the optimal time to initiate neoadjuvant chemotherapy (TTNC) is unknown. This study evaluates the association between TTNC and survival in patients with early TNBC. METHODS: A retrospective study using data from of a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018 registered in the Tumor Centre Regensburg was performed. Data included demographics, pathology, treatment, recurrence, and survival. Interval to treatment was defined as days from pathology diagnosis of TNBC to first dose of neoadjuvant chemotherapy (NACT). The Kaplan-Meier and Cox regression methods were used to evaluate the impact of TTNC on overall survival (OS) and 5 year OS. RESULTS: A total of 270 patients were included. Median follow up was 3.5 years. The 5-year OS estimates according to TTNC were 77.4%, 66.9%, 82.3%, 80.6%, 88.3%, 58.3%, 71.1% and 66.7% in patients who received NACT within 0-14, 15-21, 22-28, 29-35, 36-42, 43-49, 50-56 and > 56 days after diagnosis. Patients who received systemic therapy early had the highest estimated mean OS of 8.4 years, while patients who received systemic therapy after more than 56 days survived an estimated 3.3 years. CONCLUSION: The optimal time interval between diagnosis and NACT remains to be determined. However, starting NACT more than 42 days after diagnosis of TNBC seems to reduce survival. Therefore, it is strongly recommended to carry out the treatment in a certified breast center with appropriate structures, in order to enable an adequate and timely care.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/patologia , Estudos Retrospectivos , Neoplasias da Mama/patologia , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica , Prognóstico , Quimioterapia Adjuvante
9.
Cancers (Basel) ; 15(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37174080

RESUMO

Checkpoint blockade is particularly based on PD-1/PD-L1-inhibiting antibodies. However, an efficient immunological tumor defense can be blocked not only by PD-(L)1 but also by the presence of additional immune checkpoint molecules. Here, we investigated the co-expression of several immune checkpoint proteins and the soluble forms thereof (e.g., PD-1, TIM-3, LAG-3, PD-L1, PD-L2 and others) in humanized tumor mice (HTM) simultaneously harboring cell line-derived (JIMT-1, MDA-MB-231, MCF-7) or patient-derived breast cancer and a functional human immune system. We identified tumor-infiltrating T cells with a triple-positive PD-1, LAG-3 and TIM-3 phenotype. While PD-1 expression was increased in both the CD4 and CD8 T cells, TIM-3 was found to be upregulated particularly in the cytotoxic T cells in the MDA-MB-231-based HTM model. High levels of soluble TIM-3 and galectin-9 (a TIM-3 ligand) were detected in the serum. Surprisingly, soluble PD-L2, but only low levels of sPD-L1, were found in mice harboring PD-L1-positive tumors. Analysis of a dataset containing 3039 primary breast cancer samples on the R2 Genomics Analysis Platform revealed increased TIM-3, galectin-9 and LAG-3 expression, not only in triple-negative breast cancer but also in the HER2+ and hormone receptor-positive breast cancer subtypes. These data indicate that LAG-3 and TIM-3 represent additional key molecules within the breast cancer anti-immunity landscape.

10.
Clin Hemorheol Microcirc ; 84(1): 103-109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970892

RESUMO

OBJECTIVE: Since the first use of silicone implants by Cronin in 1962, there have been several attempts to introduce alternative filling materials for breast implants on the market. A promising new development are lightweight implants, whose filler material is one third lighter than conventional silicone gel. While these implants have been used primarily for aesthetic augmentation, a benefit could be expected particularly in post-mastectomy reconstruction. MATERIALS AND METHODS: Since 2019, 92 operations using lightweight implants have been performed at our clinic, 61 of them for breast reconstruction after mastectomy. These have been compared to 92 breast reconstructions using conventional silicone implants. RESULTS: The average volume of the lightweight implants was 30% higher than of the conventional implants (452 ml resp. 347 ml), whereas the implant weight was comparable in both groups (317 g resp. 347 g). Grade 3-4 capsular fibrosis was seen in 6 cases in both groups; revision was required 9 times (lightweight implants) and 7 times (conventional silicone implants) during the follow-up period. DISCUSSION: To our knowledge, this is the first study to investigate the use of lightweight implants in breast reconstruction. With exception of the filler material, the implants used in the two groups were comparable in shape and surface. The inserted lightweight implants had a greater volume but nearly the same weight as the conventional implants and were used in patients with a higher body mass index. Thus, lightweight implants were preferred in patients whose reconstruction required a larger implant volume. CONCLUSION: Lightweight implants are a new alternative for breast reconstruction especially in case that larger implant volume is demanded. The increased complication rate has to be verified in further studies.


Assuntos
Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Implantes de Mama/efeitos adversos , Mastectomia , Neoplasias da Mama/cirurgia , Géis de Silicone
11.
Br J Cancer ; 128(6): 1134-1147, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36572733

RESUMO

BACKGROUND: Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. METHODS AND RESULTS: In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). CONCLUSION: The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Pancreáticas , Humanos , Ductos Biliares Intra-Hepáticos , Neoplasias Pancreáticas
12.
Arch Gynecol Obstet ; 307(6): 1949-1955, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36503976

RESUMO

PURPOSE: As breast-conserving surgery (BCS) has become the standard for treatment of early breast cancer, the need for new technologies to improve intraoperative margin assessment has become clear. Close or positive margins during BCS lead to additional surgeries, treatment delay, additional stress for patients and increasing healthcare cost. Automated three-dimensional breast ultrasound (ABUS) systems are meant to overcome the shortcomings of hand-held ultrasound (HHUS). In this study, we investigate the feasibility of ABUS to conduct ultrasound on surgical specimens in breast conserving therapy. METHODS: In this monocentric, non-interventional study, specimens of 40 women were examined via ABUS. A construction with isotonic saline solution, gel pads and ABUS membranes was invented by our team to produce images of breast cancer specimens using ABUS. Evaluation of the ABUS images was carried out by two independent physicians trained on ABUS evaluation. RESULTS: ABUS was conducted on 40 specimens. 90% of the generated images were of high quality. Measured tumor sizes with ABUS were bigger than measured tumor size with HHUS (mean tumor size 22.9 vs. 18.1 mm, CI 2.38-7.35, p < 0.05). The mean difference between the ABUS tumor size and the pathological tumor size was 1.8 mm (CI - 0.84-4.53, p = 0.17). The mean difference between the HHUS tumor size and the pathological tumor size was 3.2 mm (CI - 5.35 to - 1.03, p = 0.005). CONCLUSION: ABUS seems to be a suitable method to conduct specimen ultrasound. Further studies are required to evaluate the accuracy of ABUS for intraoperative margin assessment and possible implementation in clinical work routine.


Assuntos
Neoplasias da Mama , Mama , Mastectomia Segmentar , Feminino , Humanos , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Sensibilidade e Especificidade , Ultrassonografia Mamária/métodos , Margens de Excisão
13.
Arch Gynecol Obstet ; 307(2): 549-555, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35635619

RESUMO

PURPOSE: Lipofilling has been established as a standard technique for contour enhancement following breast reconstruction. However, there is a paucity in current literature regarding the use of this technique for complete reconstruction of the female breast as an alternative to conventional techniques, such as expander or flap-based procedures. In particular, the influence of pre-operative irradiation for successful reconstruction has rarely been examined in published studies. Here, the authors describe their experience with successful fat injection in pre-radiated breasts in comparison with non-pre-radiated patients. METHODS: In this retrospective study, we examined a total of 95 lipofilling treatments on 26 patients (28 breasts). All of them experienced mastectomy following breast cancer; local breast defects after partial resection of the gland were not included in this study. In total, 47 lipofilling procedures in 12 non-irradiated patients (14 breasts) and 48 procedures in 14 irradiated women (also 14 breasts) were performed. Per session, approximately 297 ± 112 cc of adipose tissue was grafted in group A (no radiotherapy) and approximately 259 ± 93 cc was grafted in group B (radiotherapy). RESULTS: Among the group of women without pre-operative radiation, 71% of breast reconstructions limited to lipofilling only showed constant engraftment of fat tissue with a successful reconstructive result, whereas only 21% of the patients with pre-radiated breasts showed complete reconstruction of the breast with a permanent fat in-growth. CONCLUSION: Preoperative radiotherapy significantly impedes successful completion of breast reconstructions planned only by autologous fat transfer. Patients should be selected individually and carefully for complete breast reconstruction using lipofilling only.


Assuntos
Neoplasias da Mama , Mamoplastia , Feminino , Humanos , Mastectomia/métodos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Mamoplastia/métodos , Tecido Adiposo
14.
Cancers (Basel) ; 14(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35565343

RESUMO

"Humanized" mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34+ stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34+ cells. Contamination ≤ 1.2% by CD3+ cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes.

16.
Aesthetic Plast Surg ; 46(5): 2228-2236, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35296928

RESUMO

AIMS: Congenital breast asymmetry represents a particular challenge to the classic techniques of plastic surgery given the young age of patients at presentation. This study reviews and compares the long-term results of traditional breast augmentation using silicone implants and the more innovative technique of lipografting. METHODS: To achieve this, we not only captured subjective parameters such as satisfaction with outcome and symmetry, but also objective parameters including breast volume and anthropometric measurements. The objective examination was performed manually and by using the Vectra® H2 photogrammetry scanning system. RESULTS: Differences between patients undergoing either implant augmentation or lipograft were revealed not to be significant with respect to patient satisfaction with surgical outcome (p = 0.55) and symmetry (p = 0.69). Furthermore, a breast symmetry of 93 % was reported in both groups. Likewise, no statistically significant volume difference between the left and right breasts was observed in both groups (p < 0.41). However, lipograft patients needed on average 2.9 procedures to achieve the desired result, compared with 1.3 for implant augmentation. In contrast, patients treated with implant augmentation may require a number of implant changes during their lifetime. CONCLUSION: Both methods may be considered for patients presenting with congenital breast asymmetry. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Implantes de Mama , Mamoplastia , Humanos , Estética , Mamoplastia/métodos , Mama/cirurgia , Silicones
17.
Arch Gynecol Obstet ; 305(4): 921-927, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34532758

RESUMO

PURPOSE: The aim of our study was to examine the surgical outcome and complications (efficiency) as well as the incidence of locoregional recurrence and distant metastases (oncological safety) in patients who underwent autologous fat grafting (AFG) of the breast following breast cancer surgery. METHODS: In our monocentric cohort study, retrospective and prospective data were collected from all consecutive patients who underwent AFG after breast cancer between 2008 and 2020; a total of 93 patients met the inclusion criteria. RESULTS: Our long-term results showed no increase in tumor recurrence and distant metastases in the studied collective when compared to the available literature. We observed 1 local recurrence (1.1%), 2 distant metastases (2.2%), and 1 tumor-related death (1.1%). There was a high degree of patient satisfaction; 67.12% of patients reported adequate satisfaction with autologous fat grafting. CONCLUSION: Currently, to our knowledge, this is the study with the longest follow-up time (mean 6.7 years after AFG and 11.5 years after tumor resection). The results of our clinical study will contribute to improve evidence in the broad field of AFG, adipose stem cell and tumor research. Consistent with our study, the literature review shows a clear tendency of clinical trial results with a low incidence rate of tumor recurrence and metastasis following the use of AFG. AFG seems to be a safe procedure also after breast cancer treatment.


Assuntos
Neoplasias da Mama , Mamoplastia , Tecido Adiposo/patologia , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Estudos Retrospectivos
18.
Arch Gynecol Obstet ; 305(1): 95-102, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480228

RESUMO

PURPOSE: Congenital breast asymmetry is a serious gynecological malformation for affected patients. The condition hits young women in puberty and is associated with socio-esthetic handicap, depression, and psychosexual problems. Surgical treatment is usually early in the patient's lifetime, so a long-term sustainable solution is important. Although postoperative outcome has been evaluated in several studies before, this study is the first to analyze which objective parameters have the greatest influence on subjective satisfaction with long-term results. METHODS: Thirty-four patients diagnosed with congenital breast asymmetry that underwent either lipofilling or implant therapy between the years of 2008 to 2019 were examined. On average, our collective comprised patients seven years after surgery. Data were mainly gathered through manual measurements, patient-reported outcome measures (Breast Q™), and breast volumetry based on 3D scans (Vectra® H2, Canfield Scientific). RESULTS: Among all analyzed parameters, only areolar diameter correlated significantly negatively with the subjective outcome satisfaction of the patient. Regarding the subjective assessment of postoperative satisfaction with similarity of the breasts, again the mean areolar diameter, but also the difference in areolar diameter and breast volume between the right and left breasts correlated significantly negatively. CONCLUSION: Areolar diameter was revealed as being a significant factor influencing subjective long-term satisfaction in breast asymmetry patients. Moreover, 3D volumetry proves to be an effective tool to substantiate subjective patient assessments. Our findings may lead to further improvements to surgical planning and will be expanded in further studies.


Assuntos
Mama , Mamoplastia , Satisfação do Paciente , Pesos e Medidas Corporais , Mama/anormalidades , Mama/patologia , Mama/cirurgia , Implantes de Mama/psicologia , Anormalidades Congênitas/patologia , Anormalidades Congênitas/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Mamoplastia/métodos , Mamoplastia/psicologia , Mamilos/patologia , Mamilos/cirurgia , Tamanho do Órgão , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento
20.
Clin Breast Cancer ; 22(2): e142-e146, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34219020

RESUMO

INTRODUCTION: The Invenia Automated Breast Ultrasound Screening (ABUS) is indicated as an adjunct to mammography for breast cancer screening in asymptomatic women with high-density breast tissue. ABUS provides time-efficient evaluation of the 3-dimensional recordings within 3 to 6 minutes. The role and advantages of ABUS in everyday clinical practice, especially in routine examination during neoadjuvant chemotherapy (NACT), is not clear. The aim of this monocentric, noninterventional retrospective study is to evaluate the use of ABUS in patients who are under NACT treatment for response control. METHODS: Regular sonographic response check with handheld ultrasound (HHUS) examination and with ABUS were conducted in 83 women who underwent NACT. The response controls were conducted every 3 to 6 weeks during NACT. The handheld sonography was performed with GE Voluson S8. Handheld sonographic measurements and ABUS measurements were compared with the final pathologic tumor size. RESULTS: There was no statistical difference between the measurements with HHUS examination or ABUS compared with final pathologic tumor size (P = .47). The average difference from ABUS measured tumor size to final pathologic tumor size was 9.8 mm. The average difference from handheld measured tumor size to final pathologic tumor size was 9/3 mm. Both the specificity of ABUS and HHUS examination in predicting pathologic complete remission was 100%. CONCLUSION: ABUS seems to be a suitable method to conduct response control in neoadjuvant breast cancer treatment. ABUS may facilitate preoperative planning and offers remarkable time saving for physicians compared with HHUS examination and thus should be considered for clinical practice.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Diagnóstico por Computador/instrumentação , Interpretação de Imagem Assistida por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Adulto , Idoso , Neoplasias da Mama/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Ultrassonografia Mamária/métodos
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