Cytomegalovirus seronegativity rate in pregnant women and primary cytomegalovirus infection during pregnancy in rural Germany.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common congenital infection worldwide and one of the leading causes of congenital hearing loss in newborns. The aim of this study was to determine the seroprevalence rate for cytomegalovirus in pregnant women and the rate of CMV serological testing utilised during pregnancy in a rural region in Germany. METHODS: Retrospective data on the prevalence of CMV IgG and IgM antibodies were obtained from 3,800 women, identified in the study group of 19,511 pregnant women from outpatient settings whose samples were collected between 1 and 2014 and 30 April 2018. In addition, the serological CMV status in regards to various billing methods was further analyzed. RESULTS: Serological CMV tests were performed in 3,800 (19.5%) out of 19,511 pregnant women. 2,081 (54.8%) of these women were CMV seronegative. Among those, seroconversion rate of 0.37-1.42% was identified. A proportion of 2,710 (14.7%) of all 18,460 women with statutory health insurance made use of the CMV testing as an individual health service. CONCLUSIONS: The low uptake of CMV serological testing in the study population covered indicates low risk awareness among pregnant women and their healthcare professionals. Presented seronegativity rates and routine seroconversion rate, demonstrate importance to improve intervention strategy to prevent feto-maternal CMV transmission.

Tumor characteristics, therapy, and prognosis in young breast cancer patients ≤ 35 years.

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.

Enhanced S100B expression in T and B lymphocytes in spontaneous preterm birth and preeclampsia.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth.

Preterm birth (PTB) is one of the most frequent pregnancy complications. It affects millions of babies each year worldwide and is associated with increased morbidity and mortality. PTB-associated alterations in the maternal immune response may have a direct effect on the developing fetal immune system. Having recently shown that B regulatory (Breg) cells are decreased in number and functionally impaired in maternal blood from women delivering preterm, we now addressed the question whether the adaptive immune system is also altered in cord blood (CB) after the onset of PTB. PTB was associated with increased concentrations of IL-6, TNF-α and IL-21 in CB and enhanced IL-6, but decreased IFN-γ and IL-4 in amniotic fluid (AF) samples compared to term delivery (TD). We found no differences in the frequency of CD19 + B cells, CD4 + T cells or CD4+Foxp3+CD25+ T regulatory (Treg) cells in CB cells in PTB vs TD. The frequency of CD86 + B cells was increased, while the percentage of CD24hiCD38hiCD19 + Breg and CD1dhiCD5+ Breg cells and the ability of B cells to convert into Breg cells was diminished in PTB compared to TD. CB B cells from PTB secreted more IL-6, TNF-α, IL-9 and IL-2 compared to B cells obtained from term samples. We conclude that, after PTB onset, a shift from immunoregulation towards inflammation takes place in CB cells that are reportedly representative of the fetal compartment. B cells have a substantial contribution herein. This phenomenon might account for the observed enhanced mortality and morbidity in prematurely born infants. Further studies will clarify how to employ this easy-to-obtain information for closely monitoring newborns at risk.

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.

Regulatory B Cells Are Decreased and Impaired in Their Function in Peripheral Maternal Blood in Pre-term Birth.

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.

Human Miscarriage Is Associated With Dysregulations in Peripheral Blood-Derived Myeloid Dendritic Cell Subsets.

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. In vitro 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. In vitro, 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 in vitro, 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.

The impact of neuropsychiatric disease on fetal growth: a case-control study.

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.

Post-Mastectomy Radiotherapy After Neoadjuvant Chemotherapy in Breast Cancer: A Pooled Retrospective Analysis of Three Prospective Randomized Trials.

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.

A randomized phase II study to determine the efficacy and tolerability of two doses of eribulin plus lapatinib in trastuzumab-pretreated patients with HER-2-positive metastatic breast cancer (E-VITA).

The E-VITA study evaluated the efficacy and tolerability of two schedules of eribulin and lapatinib in patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer. This multicenter, open-label phase II trial, randomly assigned patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer to lapatinib 1000 mg daily with eribulin 1.23 mg/m (equivalent to 1.4 mg/m eribulin mesylate) days 1+8 every 21 days (split-dose arm) or eribulin 1.76 mg/m (equivalent to 2.0 mg/m eribulin mesylate) day 1 every 21 days (3-weekly arm). Time to progression and tolerability were defined as primary end points; no sample size calculation for formal comparison of efficacy data has been performed. Secondary end points included objective response rate, clinical benefit rate, and overall survival. Overall, 43 patients of a planned number of 80 patients were recruited. At a median follow-up of 28.7 months, the median time to progression was 8.1 months [95% confidence interval (CI): 4.8-9.4] in the split-dose arm and 6.5 months (95% CI: 4.6-13.4) in the 3-weekly arm. Objective response rate was 52.4% (95% CI: 31.0-73.7) in the split-dose arm and 45.0% (95% CI: 23.2-66.8) in the 3-weekly arm, and clinical benefit rate was 71.4% (95% CI: 52.1-90.8) and 75.0% (95% CI: 56.0-94.0), respectively. Overall survival was also similar in both arms. The most frequent grade 3-4 adverse events were neutropenia (58.5%) and leukopenia (39.0%). The combination of eribulin and lapatinib showed an acceptable safety profile with less toxicity observed in the eribulin 1.23 mg/m day 1+8 group. This might be an alternative regimen when other treatment options are exhausted. Therefore, further clinical studies are warranted.

Tamoxifen treatment for male breast cancer and risk of thromboembolism: prospective cohort analysis.

PURPOSE: Thromboembolism is a common adverse event in women treated with tamoxifen (TAM) for breast cancer. The risk in male breast cancer patients is poorly investigated. We aimed to examine the risk of thrombotic events after TAM in male breast cancer patients. PATIENTS AND METHODS: In this prospective cohort study, 448 patients treated between May 2009 and July 2017 for male breast cancer (BC) were assessed for eligibility. Patients with follow-up shorter than 6 months were excluded. The cumulative risk of thromboembolism was evaluated. RESULTS: The median follow-up was 47 months (range 6-101 months) with a median age of 69.4 years (range 27-89 years). Oestrogen receptor and progesterone receptor expression levels were observed in 98.3 and 94.9% of cases, respectively. During the follow-up period, thrombotic events were documented in 21 (11.9%) of 177 patients receiving TAM and in 1 (2.5%) of 41 patients who did not receive tamoxifen. The estimated incidence was 51.9 per 1000 person-years and 21.5 per 1000 person-years, respectively. Notably, the highest risk was identified in the first 18 months, where 81% of the observed thrombotic events occurred. Patients aged older than 71 years had a significantly increased risk of thrombotic event under TAM treatment than their younger counterparts (p = 0.033). History of thrombotic event, cardiovascular and liver disease, as well as additional adjuvant treatment were not associated with increased thrombotic risk. CONCLUSION: The risk of thrombotic event in men treated with TAM for breast cancer is markedly increased in the first 18 months of treatment, and should be considered during treatment decisions.

Oral etoposide for metastatic choriocarcinoma: a case report and review of guidelines.

BACKGROUND AND PURPOSE: Choriocarcinoma (CCA) is a rare form of malignant trophoblastic disease. Systemic polychemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) is the mainstay of treatment for metastatic disease. Due to the rarity of the condition, however, the evidence basis for this management is small and other chemotherapy regimens may also be effective. The reported case presents anecdotal evidence of an effective etoposide monotherapy treatment. METHOD: CASE PRESENTATION: We report the case of a patient with gestational choriocarcinoma and pulmonary metastases initially treated with methotrexate. Due to local disease progression, she underwent hysterectomy and continued treatment with methotrexate. After pulmonary progression, she was switched to oral etoposide. RESULTS: After four cycles of etoposide monotherapy at a oral dosage of 100 mg d1-7, q28, the patient had no evidence of disease according to human chorionic gonadotropin serum levels and imaging studies. The treatment was well tolerated with World Health Organization (WHO) grade 2 alopecia and hot flushes as the most prominent side effects. The patient has achieved a sustained complete remission with a follow-up of 6 years. CONCLUSION: Oral etoposide may be an effective treatment alternative to EMA/CO in selected patients with oligometastatic CCA.

Endometrial cancer subtypes are associated with different patterns of recurrence.

PURPOSE: To evaluate the pattern of endometrial cancer recurrence according to its biological subtype in a large cohort of patients. PATIENTS AND METHODS: Patients were stage eligible if they had a description of registry risk of recurrence status and were not primary metastatic. Data were prospectively collected. The primary endpoints were the subtype-dependent pattern and time of recurrence. RESULTS: The median follow-up time was 84 months. The highest 10-year recurrence-free and overall survival were seen in the group of patients at low risk of recurrence, 83.1 and 94.1%, respectively. The 10-year recurrence-free survival for intermediate and high risk group was 65.7 and 56.2%, respectively, whereas the estimated 10-year overall survival for both groups was 84.5 and 79.3%, respectively. Patients at high risk demonstrated the highest levels of disease recurrence in the first 3-4 years after diagnosis and the most common site of metastasis was the lung. In contrast, the rate of recurrence for patients at intermediate and low risk of recurrence in the first 5 years was relatively low but remained continuous up to 10 years of follow-up. Overall, the most common site of relapse was local recurrence. CONCLUSION: Endometrial cancer subtypes are associated with different times and patterns of recurrence and this should be considered when determining the treatment strategy.

BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study.

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Ovarian metastasis in patients with endometrial cancer: risk factors and impact on survival.

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.

Does ultrasound-guided intervention during repeat cesarean sections improve uterine scar architecture and reduce the number of scars? A prospective controlled clinical intervention trial.

Purpose To evaluate whether intraoperative ultrasound-guided detection and resection of the uterine scar during repeat/second cesarean can reduce the number of scars and improve uterine scar architecture. Materials and methods A prospective controlled clinical intervention trial was performed with the following groups: control group 1 (CS1-G): first cesarean; control group 2 (CS2-G): second cesarean utilizing the usual procedure and intervention group (Int-G): repeat/second cesarean with intervention. Transvaginal ultrasound scans were performed 6-9 months after each cesarean. Both primary (double scarring rate) and secondary outcomes [deficiency ratio=d/(b+d)] were analyzed. The deficiency ratio describes the thinning of the remaining myometrium (d=residual myometrial thickness) over the "apparent" defect (b=scar depth). Results In total, 124 of the 156 recruited women were examined, eight were excluded from analysis. The double scarring rate decreased from 42.9% (12/28) in CS2-G to 7.1% (2/28) in the Int-G [difference: 35.8%; 95% confidence interval (CI) (13.2, 54.5); P=0.002]. Two-way analysis of variance (ANOVA) revealed a significant difference between CS2-G and the Int-G in the deficiency ratio adjusted for elective/primary cesareans, with thicker remaining myometrium over the scar defect in the Int-G [difference: -0.24; 95% CI (-0.34, -0.15); P<0.001]. Conclusion Ultrasound-guided resection of the uterine scar area during repeat cesareans reduces the scarring rate and improves thickness of the remaining myometrium as detected by ultrasonography 6-9 months postoperatively.

A comparison of tumour size measurements with palpation, ultrasound and mammography in male breast cancer: first results of the prospective register study.

PURPOSE: Precise presurgical diagnosis of tumour size is essential for adequate treatment of male breast cancer (MBC). This study is aimed to compare the accuracy of clinical measurement (CE), ultrasound (US) and mammography (MG) for preoperative estimation of tumour size. METHODS: This study was conducted as a prospective, multicentre register study. One hundred and twenty-nine male patients with invasive breast cancer were included. CE, US and MG were performed in 107, 110 and 75 patients, respectively, and the estimated tumour size was compared with the histopathological (HP) tumour size. RESULTS: All methods tended to underestimate the HP tumour size. None of the methods were significantly more accurate than the others in determining the maximal tumour diameter. The sensitivity within 5 mm tolerance for US was 65.5%, which was better than for MG (61.3%) and CE (56.6%). In the group of patients with pT2 tumours, MG showed significantly better accuracy than US. The measurements obtained with each method were significantly correlated with the HP measurements. The highest correlation coefficient was observed for MG (0.788), followed by US (0.741) and CE (0.671). CONCLUSIONS: Our data demonstrate that MG and US have similar accuracy with regard to tumour size estimation. US assessment showed the highest sensitivity in determining tumour size, followed by MG and CE. However, MG demonstrated a significant advantage for estimating the real tumour size for pT2 tumours compared to US or CE.

Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer.

BACKGROUND: Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). PATIENTS AND METHODS: We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. RESULTS: The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028). CONCLUSIONS: The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

Pregnancy Outcomes in Maternal Neuropsychiatric Illness and Substance Abuse.

INTRODUCTION: Worldwide the prevalence of neuropsychiatric illness among women of reproductive age is higher than ever before. This study investigates the influences of maternal substance abuse/dependence and neuropsychiatric illness on pregnancy and neonatal outcomes. PATIENTS AND METHODS: Using a retrospective study design 185 pregnancies in women with neuropsychiatric illnesses or substance abuse were identified at a single centre over a period of 3.25 years and compared to 4907 pregnancies in healthy women without mental illness. Differences in pre-, peri- and postnatal pregnancy parameters were studied. RESULTS: Numbers of previous abortions on obstetric history were significantly higher in cases compared to controls, women with depression being especially affected. The number of antenatal visits was also higher among cases, especially in women with depression. The caesarean section rate was significantly higher in cases compared to controls. Children of women with neuropsychiatric illness were born at lower gestational ages than those of healthy control mothers, however there were no significant differences between case and control groups for birth weight, head circumference or Apgar scores. Some isolated differences were found for disease-specific case subgroups compared to controls. CONCLUSION: The study shows a relationship between maternal neuropsychiatric illness and pregnancy outcomes independent of medication use. Rates of spontaneous abortion were higher. Children were born earlier, yet the neonatal outcomes birth weight, head circumference and Apgar score were not worse than children of mentally healthy women.

Management of elderly women with endometrial cancer.

BACKGROUND: Elderly women with endometrial cancer receive less therapy in comparison with their younger counterparts. The exact reason(s) for this treatment strategy remains unclear. PATIENTS AND METHODS: We performed a multicenter, retrospective registry-based study of 1550 patients with endometrial cancer. The outcome measure was the reason for not performing the indicated treatment. RESULTS: Median follow-up was 76.8months. A total of 1550 women were eligible for analysis: 353 (22.7%) were younger than 60years, 521 (33.6%) 61-70years, 515 (33.2%) 71-80years, and 161 (10.4%) were aged 81years old and older. Elderly women were more likely to have non-endometrioid, undifferentiated endometrial cancer at an advanced stage. Patients younger than 60years were more likely to receive lymphadenectomy, brachytherapy, external-beam radiotherapy (EBRT) and systemic therapy compared with the group of patients aged older than 70years. We investigated the reason why elderly women were undertreated. The rate of indicated therapies that were not recommended by the physicians proportionally increased with an increase in patient age. Interestingly, the rate of contraindications because of performance status and/or medical disease also increased proportionally with increasing patient age. Notably, in the groups of patients older than 70years, patient refusal was a very uncommon reason for failure to perform the indicated therapy. CONCLUSIONS: Elderly women with EC are more likely undertreated because the therapy was not recommended by the physicians based on performance status and medical diseases rather than patient refusal.