To determine the impact of adjuvant treatment with tamoxifen and aromatase inhibitors (AI) on the survival of men with breast cancer. We analyzed 257 male patients with hormone-receptor-positive ...breast cancer from numerous German population-based cancer registries treated with tamoxifen (
N
= 207) or aromatase inhibitors (
N
= 50). The median follow-up was 42.2 (range 2–115) months. Median age at diagnosis was 68 (range 36–91) years. Thirty-seven (17.9 %) patients treated with tamoxifen and 16 (32.0 %) patients treated with AI died (log rank
p
= 0.007). After the adjustment for the patient’s age, tumor size, node status, and tumor grading, the AI treatment was linked to a 1.5-fold increase in risk of mortality compared to tamoxifen (HR 1.55; 95 % CI: 1.13–2.13;
p
= 0.007). The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. Tamoxifen should be considered as the treatment of choice for hormone-receptor-positive male breast cancer.
S100B belongs to the family of danger signaling proteins. It is mainly expressed by glial-specific cells in the brain. However, S100B was also detected in other cell likewise immune cells. This ...molecule was suggested as biomarker for inflammation and fetal brain damage in spontaneous preterm birth (sPTB), preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, and low platelet count).
The aim of our study was to determine the concentration of S100B in maternal and cord blood (CB) plasma and placenta supernatant as well as the expression of S100B in maternal and CB CD4+ T cells and CD19+ B cells in sPTB and patients delivering following PE/HELLP diagnosis compared to women delivering at term (TD). The S100B expression was further related to the birth weight in our study cohort.
S100B concentration was enhanced in maternal and CB plasma of sPTB and PE/HELLP patients and positively correlated with interleukin-6 (IL-6) levels. Increased S100B was also confirmed in CB of small-for-gestational-age (SGA) infants. S100B expression in maternal blood was elevated in CD4+ T cells of PE/HELLP patients and patients who gave birth to SGA newborns as well as in CD19+ B cells of sPTB and PE/HELLP patients and patients with SGA babies. In CB, the expression of S100B was increased in CD19+ B cells of sPTB, PE/HELLP and SGA babies.
Our results support the hypothesis that S100B expression is enhanced in inflammatory events associated with preterm birth and that S100B expression in immune cells is a relevant marker for inflammation during pregnancy complications.
Purposes
Young breast cancer patients aged 35 years and younger are a small group of women who tend to present at high-risk form of the disease. More analysis of the data on tumor characteristics, ...treatment, and survival is necessary to help improving treatment and outcome.
Methods
In this retrospective study, we compared the clinical and tumor characteristics, the treatments, and the survival of 257 women aged ≤ 35 years, with 6566 women aged 50–69 years. We used a registry-based data of patients with invasive, non-metastatic breast cancer diagnosed between 2000 and 2015.
Results
Young women showed lower rate of hormone receptor (HR) positivity. Their tumors were more often HER2-positive, which showed lower rate of differentiation and higher rate of Ki-67 expression compared to their older counterparts. Women aged 35 years and younger were more likely to undergo neoadjuvant therapy and mastectomy. Endocrine therapy was underrepresented in young patients. 5-Year disease-free survival (DFS) was significantly lower in the younger patient group (81.7% vs. 91.3%,
p
< 0.001), while 5-year overall survival (OS) was not impaired (91.4% vs. 91.1%,
p
= 0.847).
Conclusion
The unfavorable disease-free survival in the group of younger patients might be explained by their unfavorable tumor characteristics. The surgical treatment appears to be more aggressive in young breast cancer patients and is more frequently combined with chemotherapy and immunotherapy, either in a neoadjuvant or in an adjuvant setting.
Dendritic cells (DC) are critically involved in decisions related to the acceptance or rejection of the foreign fetal antigens by the maternal immune system. However, particularly for human ...peripheral blood DCs (PBDC), available literature is rather inconsistent and the factors regulating these cells are ill-defined. Here, we investigated the phenotype and functionality of different human PBDC subsets during normal and pathologic pregnancies and studied an involvement of human chorionic gonadotropin (hCG) in PBDC regulation. Peripheral blood samples were obtained from normal pregnant women in all three trimesters, from first trimester miscarriage patients and from healthy non-pregnant women. Samples were analyzed for plasma hCG levels, for regulatory T (Treg) cell numbers, for frequencies of total and mature plasmacytoid (PDC) and myeloid (MDC1 and MDC2) PBDC subsets and for their cytokine secretion.
assays, culturing PDC, MDC1 or MDC2 in the presence of two trophoblast cell lines, placenta explant supernatants or two hCG preparations were performed. The Treg-inducing capability of hCG- or non-hCG-treated stimulated MDC1 was assessed. Total and mature MDC1 and MDC2 frequencies increased during the first and second trimester of normal pregnancy, respectively. Miscarriage was associated with a reduced MDC1 and an increased MDC2 activation profile. PDC were not altered neither during normal pregnancy progression nor during miscarriage.
, the culture of isolated PBDC subsets in the presence of placenta-derived factors impaired the maturation of MDC1 and differentially affected PDC maturation. An inhibitory effect on MDC1 and PDC maturation was also proven for the urine-derived hCG preparation. Finally, we observed a Treg cell elevation during early normal pregnancy that was not present in miscarriages. Stimulated MDC1 induced Treg cells
, however, hCG was not involved in this process. Our findings suggest that during normal pregnancy PBDC subsets are differentially regulated dependent on gestational age. Miscarriage seems to be associated with dysregulations in the myeloid PBDC subsets and with disturbances in Treg cell frequencies. Moreover, our results propose an interdependency between MDC1 and Treg cells during early pregnancy. hCG, although shown to impair MDC1 maturation, does not seem to be a key regulator of PBDC alterations during pregnancy.
Background
Oophorectomy is generally performed in patients with endometrial cancer despite the rate of ovarian metastasis being relatively low.
Patients and methods
A multicenter retrospective ...registry-based study was performed in 2329 patients with endometrial cancer. The outcome measures were the incidence of ovarian metastasis and the impact on overall survival.
Results
Median follow-up was performed at 84 months. A total of 2158 women were eligible for analysis, of which 131 (6.1%) had ovarian metastasis. Women with ovarian metastasis were more likely to have > 50% myometrial invasion, undifferentiated nonendometrioid tumors, and lymph and vascular space invasion. The presence of < 50% myometrial invasion, endometrioid histology, well-differentiated cancer, and negative lymph and vascular space invasion were associated with a very low rate (0.5%) of ovarian metastasis. Notably, after matching for tumor histology and grade, myometrial invasion, and lymph and vascular space invasion, ovarian metastasis was not associated with a reduced median overall survival.
Conclusions
Ovarian preservation should be offered to premenopausal women with endometrial cancer in whom myometrial invasion is less than 50%, the histological type is endometrioid and well-differentiated, and lymph and vascular space invasion is not involved.
Preterm birth (PTB) is defined as birth before 37 completed weeks of gestation. The causes of PTB are multiple and complex, the underlying pathophysiology being largely unknown. Interferences in the ...fine-tuned balance of the maternal immune system have been pointed to as one possible cause of PTB. Regulatory B cells (Breg) are part of the adaptive immune response, and recent data suggest that they may contribute to a healthy pregnancy by their regulatory/suppressive function. We investigated the frequency of Breg cells in peripheral blood of women undergoing PTB and control women immediately before giving birth via cesarean section. We detected an enhanced number of B cells, but a reduced number of Breg cells in women delivering preterm. In addition, the percentage of IL-10-producing B cells was decreased in PTB following stimulation with TLR agonists CpG or LPS, alone or combined with CD40L. This was associated with increased levels of pro-inflammatory cytokines in maternal serum. Moreover, isolated maternal B cells before delivering premature babies secreted higher level of the pro-inflammatory cytokine IL-6. No alterations in the frequency of regulatory T cells were found. Our data indicate that alterations in the number and function of Breg cells in peripheral maternal blood contribute to the immunological changes observed in preterm delivery and suggest these cells as important regulators of maternal immune responses.
Regulatory T cells (Treg) expand during pregnancy and are present at the fetal-maternal interface at very early stages in pregnancy. The migration mechanisms of Treg to the pregnant uterus are still ...unclear. Human chorionic gonadotropin (hCG) is secreted by the blastocyst immediately after fertilization and has chemoattractant properties. Therefore, we sought to analyze whether hCG secreted by early trophoblasts attracts Treg to the uterus and hence contributes to maternal tolerance toward the fetus. Decidua and placenta tissue samples from patients having spontaneous abortions or ectopic pregnancies were employed to evaluate Treg and hCG levels. Age-matched samples from normal pregnant women served as controls. We further performed in vitro studies with primary first trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to evaluate the ability of secreted hCG to attract Treg. Patients having miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-beta mRNA levels as compared with normal pregnant women. Using migration assays we demonstrated that Treg were attracted by hCG-producing trophoblasts or choriocarcinoma cells. Treg migration toward cells transfected with hCG expression vectors confirmed the chemoattractant ability of hCG. Our data clearly show that hCG produced by trophoblasts attracts Treg to the fetal-maternal interface. High hCG levels at very early pregnancy stages ensure Treg to migrate to the site of contact between paternal Ags and maternal immune cells and to orchestrate immune tolerance toward the fetus.
Purpose
To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric ...diseases and drug abuse, the number of affected pregnant women is increasing.
Methods
A large-scale retrospective case–control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference.
Results
Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication.
Conclusion
The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself.
Background
The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that ...patients with a favorable response to NACT might not benefit from RT after mastectomy.
Methods
A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%).
Results
The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval CI 9.0–22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7–14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27–1.0;
p
= 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis.
Conclusions
Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.
Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. ...The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2- expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR- breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052-1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926-1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated.
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