Impact of cavity shaving on residual tumor rates in patients with primary invasive carcinoma and carcinoma in situ in breast conserving surgery.

BACKGROUND: Several international studies reported relatively high re-excision rates due to residual tumor in breast conserving surgery (BCS). Cavity shaving (CS) is a surgical strategy to reduce re-excision rates. This study aimed to investigate the effect of circumferential cavity shaving during BCS to reduce residual tumor. MATERIAL AND METHODS: A total of 591 patients with early invasive carcinoma or carcinoma in situ of the breast (ICD-10, C50 or D05) who were diagnosed between 01/01/2017 and 31/12/2019 and underwent BCS in a certified breast cancer center of the University Regensburg were analyzed regarding surgical excision methods. Patients with CS during BCS and patients with targeted re-excision in a specific direction depending on the result of intraoperative mammography or sonography during BCS were compared. The risk of pathologic residual tumor (R1) was compared between both groups by means of a multivariable binary logistic regression model to determine if there is a benefit of a certain surgical method to avoid a second intervention for re-excision. We adjusted for age, tumor size, nodal status, histologic type, surgeon, breast side, and neoadjuvant chemotherapy. RESULTS: 80 (n = 13.54%) patients had CS and 511 (n = 86.46%) had a targeted re-excision in a specific direction during BCS according to intraoperative mammography or sonography. After comparing both techniques in a multivariable regression model, there was no significant difference regarding risk of residual tumor (p = 0.738) in the total cohort. However, CS showed a tendency to be favorable regarding rates of residual tumor in patients with invasive breast cancer between 60 and 70 years (p = 0.072) and smaller T1-tumors (p = 0.057) compared to targeted intraoperative re-excision following mammographic or sonographic assessment. CONCLUSION: CS showed a tendency to reduce residual tumor compared to the standard technique of intraoperative re-excision in specific subgroups, although no statistical significance was reached. Further studies are needed to overcome potential limitations like surgeon-based bias and missing standardized definitions of CS to reduce residual tumor rates.

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection.

The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19-/-, BMyD88-/- and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19-/-, BMyD88-/- and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Survival Advantage of Lymphadenectomy in Patients with Ovarian Cancer.

We investigated the survival effect of lymphadenectomy in ovarian cancer. The five-year progression-free and overall survival in early-stage ovarian cancer were not affected. Preliminary, unadjusted analysis in advanced ovarian cancer suggested an improvement in survival. However, after adjusting for other factors, e.g. ECOG performance status and patients' age, this survival advantage vanished. Our analysis suggests that systemic pelvic and para-aortic lymphadenectomy was not associated with an improvement of the progression-free and overall survival of patients with optimally debulked ovarian cancer.

Protective effect of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.

Adjuvant radiotherapy and local recurrence in vulvar cancer - a subset analysis of the AGO-CaRE-1 study.

BACKGROUND: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. PATIENTS AND METHODS: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. RESULTS: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). CONCLUSION: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV- tumors.

Factors influencing treatment decision and guideline conformity in high-grade endometrial cancer patients: a population-based study.

PURPOSE: Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. METHODS: The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. RESULTS: Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. CONCLUSION: Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

BACKGROUND: The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. PATIENTS AND METHODS: We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. RESULTS: The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1-7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. CONCLUSION: Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Role of Pelvic Lymph Node Resection in Vulvar Squamous Cell Cancer: A Subset Analysis of the AGO-CaRE-1 Study.

BACKGROUND: As the population at risk for pelvic nodal involvement remains poorly described, the role of pelvic lymphadenectomy (LAE) in vulvar squamous cell cancer (VSCC) has been a matter of discussion for decades. METHODS: In the AGO-CaRE-1 study, 1618 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB or higher primary VSCC treated at 29 centers in Germany between 1998 and 2008 were documented. In this analysis, only patients with pelvic LAE (n = 70) were analyzed with regard to prognosis and correlation between inguinal and pelvic lymph node involvement. RESULTS: The majority of patients had T1b/T2 tumors (n = 47; 67.1%), with a median diameter of 40 mm (2-240 mm); 54/70 patients (77.1%) who received pelvic LAE had positive groin nodes. For 42 of these 54 patients, the number of affected groin nodes had been documented as a median of 3; 14/42 (33.3%) of these patients had histologically confirmed pelvic nodal metastases (median number of affected pelvic nodes 3 [1-12]). In these 14 patients, the median number of affected groin nodes was 7 (1-30), with a groin metastases median maximum diameter of 42.5 mm (12-50). Receiver operating characteristic analysis showed an area under the curve of 0.85, with 83.3% sensitivity and 92.6% specificity for the prediction of pelvic involvement in cases of six or more positive groin nodes. No cases of pelvic nodal involvement without groin metastases were observed. Prognosis in cases of pelvic metastasis was poor, with a median progression-free survival of only 12.5 months. CONCLUSION: For the majority of node-positive patients with VSCC, pelvic nodal staging appears unnecessary since a relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease.

Age, treatment and prognosis of patients with squamous cell vulvar cancer (VSCC) - analysis of the AGO-CaRE-1 study.

BACKGROUND: Despite an increasing incidence with simultaneous decreasing age of onset, vulvar squamous cell carcinoma (VSCC) is still a disease that mainly effects the elderly population. Data on the association of age with prognosis and treatment patterns in VSCC are sparse. METHODS: This is an analysis of the AGO-CaRE-1 cohort. Patients with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998 to 2008, were included in a centralized database (n = 1618). In this subgroup analysis patients were analyzed according to age [<50 yrs. (n = 220), 50-69 yrs. (n = 506), ≥70 yrs. (n = 521)] with regard to treatment patterns and prognosis. Only patients with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. RESULTS: At first diagnosis, women ≥70 yrs. presented with more advanced tumor stages (<0.001), larger tumor diameter (<0.001), poorer ECOG status (<0.001), more frequent HPV negative tumors (p = 0.03) as well as a higher rate of nodal involvement (<0.001). Disease recurrence occurred significantly more often in elderly patients (p = 0.001) and age as well as ECOG status, microscopic residual resection, tumor stage, grading, and (chemo)radiation were independent prognostic factors for death or recurrence in multivariate analysis. 2-year disease-free survival rates were 59.3% (≥70 yrs), 65.8% (50-69 yrs) and 81.1% (<50 yrs), respectively (p < 0.001). CONCLUSIONS: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year DFS in comparison to younger patients. Potential reasons could be self-awareness and/or more aggressive tumor biology due to HPV independent disease.

p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group.

BACKGROUND: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed. OBJECTIVE: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance. STUDY DESIGN: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction. RESULTS: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53- (n=132), and p16-/p53- (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53- tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16-/p53- tumors; P<.0001) and showed lower rates of lymph-node involvement (28.0% vs 42.3% for p53+, respectively, 30.2% for p16-/p53- tumors; P=.050). Notably, 2-year-disease-free and overall survival rates were significantly different among the groups: disease-free survival, 47.1% (p53+), 60.2% (p16-/p53-), and 63.9% (p16+/p53-) (P<.001); overall survival, 70.4% (p53+), 75.4% (p16-/p53-), and 82.5% (p16+/p53-) (P=.002). In multivariate analysis, the p16+/p53- phenotype showed a consistently improved prognosis compared with the other groups (hazard ratio, 0.66; 95% confidence interval, 0.44-0.99; P=.042). CONCLUSION: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

Comparison of survival outcomes and effects of therapy between subtypes of high-grade endometrial cancer - a population-based study.

BACKGROUND: Similarities in outcome between grade 3 endometrioid cancer and non-endometrioid histologies have been reported by a number of studies. Other reports, however, stated a significantly better prognosis for G3 endometrioid compared to type II histology. In this population-based study, we compared the outcome and treatment approaches of high-grade endometrial cancer patients with FIGO stages I-III depending on their histology. MATERIAL AND METHODS: 284 high-grade endometrial cancer patients diagnosed between 1998 and 2015 were retrospectively analyzed. Overall survival (OS), recurrence-free survival (RFS), and recurrence rates were compared depending on histology. RESULTS: Type I G3 patients had a statistically significant OS advantage over women suffering from type II carcinoma (HR 1.527, 95%-CI 1.024-2.276; p = 0.038) and carcinosarcoma (HR 2.106, 95%-CI 1.270-3.493; p = 0.004) in univariable and multivariable Cox-regression analysis. RFS in Type I G3 was significantly superior compared to patients with carcinosarcoma (HR 1.719, 95%-CI 1.018-2.901; p = 0.043) and not significantly superior to type II patients (HR 1.368, 95%-CI 0.920-2.036; p = 0.122). Cumulative recurrence rates were significantly higher in carcinosarcoma compared to type I G3 (HR 2.217, 95%-CI 1.096-4.485; p = 0.027) in univariable analysis, but not after risk adjustment (HR of 1.472, 95%-CI 0.654-3.311; p = 0.350). CONCLUSION: The prognosis of patients with type I G3 endometrial cancer patients seems to be significantly superior to patients with type II cancer and particularly carcinosarcoma. Systematic LND seemed to be beneficial in all of the three subtypes. The benefit of adjuvant treatment methods may differ between histologies.

Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases.

INTRODUCTION: The risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed. MATERIAL AND METHODS: We performed a multicenter, retrospective registry-based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non-SLN metastases in the case of positive unilateral SLN. RESULTS: Out of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy-18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1-4) per patient and 76 of these were positive. Lymph node-positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino-femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10-29) per patient. After full dissection of the inguino-femoral lymph nodes, no contralateral non-SLN metastases were found. CONCLUSIONS: The risk of contralateral non-SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies.

Minimal-invasive or open approach for surgery of early cervical cancer: the treatment center matters.

PURPOSE: The aim of the study was to compare recurrence-free survival (RFS) and overall survival (OS) of patients with early stage cervical cancer in dependence of surgical approach and treatment center. PATIENTS AND METHODS: A population-based cohort study including women with early stage IA1-IIB2 cervical cancer treated by radical hysterectomy between January 2010 and December 2015 was performed. RESULTS: The median follow-up time was 5.6 years. After exclusions, 413 patients were eligible for analysis: 111 (26.9%) underwent minimal-invasive surgery (MIS) and 302 (73.1%) open surgery. Both treatment groups were well balanced regarding the clinical and pathological characteristics. The mean age of the patients was 51.0 years. MIS was associated with improved RFS and OS compared with the open surgery. The 5-year RFS rates were 89.2% in the MIS group and 73.4% in the open surgery group (p = 0.004). The 5-year OS rates were 93.7% in the MIS group and 81.8% in the open surgery group (p = 0.016). After adjustment for other prognostic covariates, the MIS was further associated with improved RFS (HR = 0.45, 95% CI 0.24-0.86; p = 0.015) but not with OS. Nevertheless, after adjustment for treatment center, the surgical approach was not associated with significant difference in RFS (HR = 0.61, 95% CI 0.31-1.19; p = 0.143). Overall survival of patients treated in university cancer centers was significantly increased compared to patients treated in non-university cancer centers. The treatment center remains a strong prognostic factor regarding RFS (HR = 0.49, 95% CI 0.28-0.83; p = 0.009) and OS (HR = 0.50, 95% CI 0.26-0.94; p = 0.031). CONCLUSIONS: The treatment center but not the surgical approach was associated with the survival of patients treated with radical hysterectomy for early stage cervical cancer.

Is there a benefit for adjuvant radio(chemo)therapy in early cervical cancer? Results from a population-based study.

PURPOSE: Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received. METHODS: The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status. RESULTS: In low-risk patients, there was no difference in OS (p = 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (p = 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (p = 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (p = 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group-both in RCT and RT groups compared to surgery alone-the effects did not prove to be significant. CONCLUSION: Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.

The impact of G protein-coupled oestrogen receptor 1 on male breast cancer: a retrospective analysis.

INTRODUCTION: The G protein-coupled oestrogen receptor 1 (GPER-1) is a potential prognostic marker in breast cancer. However, its role in male breast cancer (MBC) is still unknown. This study evaluates the expression of GPER-1 in MBC samples and correlates these data with clinical and pathological parameters including patients' survival. MATERIAL AND METHODS: For this retrospective analysis of a prospectively maintained cohort of patients with MBC, we examined 161 specimens for GPER-1 expression using immunohistochemistry. An immunoreactive score (IRS) was calculated based on staining intensity and the percentage of positive tumour cells. Then, we correlated GPER-1 IRS with clinical and pathological parameters, and overall and relapse-free survival. RESULTS: About 40% of MBC samples were positive for GPER-1 expression (IRS ≥ 4). There was no significant correlation with clinicopathological parameters, such as hormone receptor status or grading. However, a statistical trend was observed for tumour size (≥ 2 cm, p = 0.093). Kaplan-Meier survival analysis revealed no significant correlation with relapse-free survival. However, there was a significant correlation with overall survival, but when we adjusted the log-rank p-value to compensate for the cut-off point optimization method, it rose above 0.1. Additionally, GPER-1-positive patients were older at diagnosis. When adjusted for age by multivariable Cox regression analysis, the significance of GPER-1 status for survival was further reduced. CONCLUSIONS: We found no significant prognostic value of GPER-1 in this MBC cohort as anticipated from studies on female BC. Future studies with higher sample size are needed to further verify a potential sex-specific role of GPER-1.

Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis.

BACKGROUND: Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients. METHODS: In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS). RESULTS: Between May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27-96 years). The median follow-up was 39 months (range 3-89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14-0.74). CONCLUSIONS: Tamoxifen treatment was associated with improved DFS for MBC patients. CLINICAL TRIAL REGISTRATION: DRKS00009536.

Comparison of survival of patients with endometrial cancer undergoing sentinel node biopsy alone or systematic lymphadenectomy.

BACKGROUND: Recently, sentinel lymph node mapping was introduced in the surgical staging of endometrial cancer as alternative to systematic lymphadenectomy. However, the survival impact of sentinel node mapping is not well characterized yet. METHODS: We performed retrospective study of 104 patients with endometrial cancer treated with sentinel lymph node alone (n = 52) or with pelvic and para-aortic lymphadenectomy (n = 52). For sentinel node mapping, indocyanine green was used. The outcome measure was disease-free survival. RESULTS: Median follow-up was 42 months. Fifty-two patients staged by sentinel lymph node mapping were matched in 1:1 ratio with 52 patients staged by lymphadenectomy using patient age, histological type, tumor stage, tumor grade and lymph and vascular space invasion as matching criteria. The median number of removed lymph node was 3 (range 1-6) and 36 (13-63) in the sentinel and lymphadenectomy group, respectively. The rate of lymph node metastases was not significantly higher in the sentinel group (19.2%) in comparison with the lymphadenectomy group (14.3%). The overall detection rate of sentinel lymph nodes was 100% with a bilateral mapping of 98.1%. Most of the 152 lymph nodes identified and removed were localized in upper paracervical pathway (n = 143, 94.1%). During the follow-up period, overall 21 (20.2%) events were observed, 8 (15.4%) in the sentinel group and 13 (25.0%) in the lymphadenectomy group. The estimated disease-free survival was 84.6% and 75.0% for patients in the sentinel and lymphadenectomy groups, respectively. The survival curves demonstrated similar disease-free survival in two groups (p = 0.774). CONCLUSION: Sentinel lymph node mapping did not compromise the outcome of patients with endometrial cancer.

Systematic lymphadenectomy in early stage endometrial cancer.

BACKGROUND: The positive effect of systematic lymphadenectomy on survival of patients with endometrial cancer is a topic of ongoing debate. METHODS: We aimed to investigate whether systemic lymphadenectomy is beneficial for patients with early endometrial cancer. For this purpose, we analyzed a population-based registry with of 2392 women with endometrioid endometrial cancer, stage I and II at intermediate and high risk of recurrence. The primary outcome measure was overall survival. RESULTS: After exclusions, 868 women were eligible for analysis. Of those, 511 and 357 were categorized as intermediate (pT1A G3 and pT1B G1-2) and high risk (pT1B G3 and pT2 G1-3) early stage endometrial cancer, respectively. Lymphadenectomy was performed in 527 (60.7%) of the cases. Patients in the lymphadenectomy group were significantly younger, presented with more tumors of intermediate or undifferentiated grade and exhibited significantly lower co-morbidity rates and Eastern Cooperative of Oncology Group (ECOG) performance status. Median follow-up was 6.7 years. Recurrence-free survival was not improved by lymphadenectomy in the intermediate and high-risk group of patients. During the follow-up period, 111 (12.8%) women had disease recurrence and 302 (34.8%) died. Systematic lymphadenectomy was associated with significant improvement of overall survival in the pT1A G3 and pT1B G3 patient subgroups. Notably, adjustment for patient age and ECOG status abolished the improvement of overall survival by systematic lymphadenectomy in all groups. Thus, lymphadenectomy did not improve recurrence-free survival in the intermediate risk or the high-risk group of patients CONCLUSIONS: Systematic pelvic and para-aortic lymphadenectomy did not improve the survival of patients with early stage I and II endometrioid endometrial cancer at intermediate and high risk of recurrence.

GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients.

PURPOSE: Endocrine therapies using tamoxifen and/or aromatase inhibitors are important therapeutic options for the targeted treatment of hormone-responsive breast cancer. In addition to nuclear estrogen receptors ERα and ß, G-protein-coupled estrogen receptor GPER-1 is a third receptor-mediating estrogen effects in breast cancer cells. The aim of this study was to examine to what extent GPER-1 expression might affect the efficacy of primary endocrine treatment of breast cancer. METHODS: GPER-1 expression was determined in tissue samples from patients with early breast cancer by means of immunohistochemistry and a GPER-1 score of ≥ 3 was considered to be positive. In a total of 165 patients, the response to a primary therapy with tamoxifen (TAM) or aromatase inhibitors (AI) was assessed by ultrasound imaging for up to 6 months. The primary endpoint of this study was the response to treatment evaluated by RECIST 1.1 criteria. RESULTS: GPER-1 expression was observed in 127 (77.0%) out of 165 cases. Based on GPER-1 expression and the type of endocrine treatment, the patients were divided into 4 groups: GPER-1 negative/TAM (12.1%), GPER-1 negative/AI (10.9%), GPER-1 positive/TAM (44.8%), and GPER-1 positive/AI (32.1%). The groups were well balanced regarding different clinical and pathological factors. After 4 and 6 months of treatment, a high level of stable disease or progressive disease was observed in the GPER-1 positive/TAM group only (p < 0.0001), whereas in the other three groups of patients, the most common objective response was classified as partial response. We observed a continuous reduction of mean tumor size in patients treated with aromatase inhibitors irrespective of the GPER-1 status and in GPER-1 negative patients treated with TAM. In contrast, in GPER-1 positive patients treated with TAM, a reduction of mean tumor size was observed only in the first 2 months after beginning of treatment. Four and six months after start of treatment, no reduction, but even a slight increase of tumor size was observed in this patients group. CONCLUSIONS: GPER-1 expression is significantly associated with a reduced effect of primary treatment with tamoxifen in breast cancer patients.