Identifying the impact of inflammatory breast cancer on survival: a retrospective multi-center cohort study.

PURPOSE: Inflammatory breast cancer (IBC) represents a rare and aggressive form of cancer with negative prognosis and high rate of recurrence. The purpose of this retrospective multi-center study was to evaluate the effect of IBC on overall and disease-free survival. Furthermore we analyzed the influence of hormone and Her2 receptor expression on inflammatory breast cancer cells on the clinical outcome of patients. METHODS: This retrospective German multi-center study included 11,780 patients with primary breast cancer recruited from 1992 to 2008. In this sub-group analysis we focused on 70 patients with IBC. RESULTS: Despite the relatively small sample size, we could confirm the aggressiveness of inflammatory breast cancer and the different clinical behavior of IBC subtypes. It could be demonstrated that the lack of expression of hormone receptors on tumor cells is associated with a more aggressive clinical course and decreased overall and disease-free survival. Higher incidence of Her2 overexpression, that is typically associated with poor prognostic outcome among women with non-IBC tumors, seems however to have no prognostic significance. CONCLUSIONS: This BRENDA sub-group analysis, on a German cohort of breast cancer patients confirmed the negative outcome of IBC and the different clinical behavior of IBC subtypes. The best management of IBC requires intensive coordination and cooperation between various clinical disciplines involved in the treatment of IBC patients. Moreover there is a need to identify IBC-specific targeted therapies to improve the curing prospects of this subtype of cancer.

Is guideline-adherent adjuvant treatment an equal alternative for patients aged >65 who cannot participate in adjuvant clinical breast cancer trials? A retrospective multi-center cohort study of 4,142 patients.

INTRODUCTION: It is well accepted that innovation in oncology is transported through randomized clinical trials (CT), furthermore there is some evidence that patients profit from participation in CT. However, especially elderly patients aged >65 usually do not have access to clinical trials; we therefore used an unselected patient cohort to investigate the following questions: (1) Is there a difference in survival parameters between study participants <65 and elderly 65-80 non-participants? (2) Is guideline-adherent adjuvant treatment an equal alternative for elderly patients aged 65-80? MATERIALS AND METHODS: This German retrospective multi-center cohort study included 4,142 patients (study participants <65 and elderly breast cancer patients 65-80) with primary breast cancer recruited from 1992 to 2008 in 17 participating breast cancer centers. RESULTS: Applying the exclusion criteria, we included 960 (23.2%) study participants (PA) <65 and 3,182 (76.8%) elderly >65. Elderly non-participants (NPA) >65 demonstrate a significantly inferior RFS [RFS: HR = 1.67; p < 0.001] and OS [OS: HR = 1.98; p < 0.001] compared to PA <65. Within the elderly group, 1,868 (58.7%) patients received guideline-adherent adjuvant treatment. When comparing guideline conform elderly >65 versus PA <65, we found no significant difference in RFS [RFS: HR = 1.17; p = 0.218] and OS [OS: HR = 1.34; p = 0.054]. In contrast, non-guideline-adherent elderly demonstrated significantly inferior survival parameters [RFS: HR = 2.06; p < 0.001] [OS: HR = 2.50; p < 0.001] compared to <65 PA. CONCLUSION: Guideline-adherent adjuvant treatment seems to be an equivalent option for elderly breast cancer patients. There is a strong association between guideline adherence and improved outcome parameters in elderly breast cancer patients.

"Pregnant and Operating": Evaluation of a Germany-wide Survey Among Female Gynaecologists and Surgeons.

The current law on the protection of expectant and nursing mothers largely rules out surgical activities during pregnancy for female doctors who perform surgical roles in hospitals. The proportion of female junior staff in gynaecology amounts to 80 %, and, for many of these women, surgical further training is not possible following official notification of an existing pregnancy. In a Germany-wide survey of female gynaecologists and surgeons using a questionnaire, it was determined to what extent female doctors worked in surgery during pregnancy, whether it led to complications in the pregnancy, when the employer was notified about the pregnancy, and what desire for change there is with regard to the law on the protection of expectant and nursing mothers. The data from 164 female doctors, of which 136 are gynaecologists and 28 surgeons, was evaluated. On average, the pregnancy was announced during the 14th week of pregnancy (WOP), and the doctor was not allowed to perform surgical activities in the 21st WOP. Female doctors in higher professional roles tended to announce the pregnancy later and ended their surgical activities later. There was no link between the time of ceasing surgical activities and an increased occurrence of complaints or complications during the pregnancy. In total, only 53 % of respondents had an appraisal during pregnancy and 75 % wanted a change in the law on the protection of expectant and nursing mothers.

Career and Family - Are They Compatible?: Results of a Survey of Male and Female Gynaecologists in Germany.

Purpose: Nowadays, most gynaecologists are female and the compatibility of job-related career and family life is an upcoming issue. The working group "Gender and Career" of the German Society for Gynaecology and Obstetrics (DGGG) designed a survey to reflect the present situation with a focus on the compatibility of career and family. Material and Methods: A web-based 74-item survey was filled out by members of the DGGG. In total, there were 1037 replies, 75 % female (n = 775) and 25 % male (n = 261) gynaecologists. Results: 62 % of the female and 80 % of the male respondents had already finished their doctoral theses and 2 % female and 13 % male had finished their PhD. Mean number of children was 1.06 (SD 1.08) in female and 1.68 (SD 1.34) in male gynaecologists. The majority of females desired day care for their children, but only 5 to 13 % of employers offer any day care. 88 % of the female and 72 % of the male physicians think that job-related career and family are not compatible. Conclusion: The majority of female gynaecologists wished to have professional child care, but most employers or other institutions do not offer this. This might be one of the reasons why career and family appear incompatible.

Evaluation of FDG-PET for detecting lymph node metastasis in uterine corpus cancer.

BACKGROUND: In order to decrease surgery-related morbidity, we evaluated the reliability of the evaluation of lymph node metastasis in patients with uterine corpus cancer by positron-emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) before surgical staging. MATERIALS AND METHODS: Patients with newly diagnosed uterine corpus cancer scheduled for surgical staging, including lymphadenectomy, underwent PET imaging within 30 days before surgery. PET results and postoperative histopathology were compared for each patient and each nodal site. Sensitivity, specificity, positive and negative predictive value (PPV/NPV) as well as accuracy of FDG-PET in predicting nodal disease was determined by joined meta-analysis of the present data and the data available in the literature. RESULTS: Of 21 patients examined, 13 patients were eligible to enter this pilot study. Only one patient had lymph node metastasis, which was preoperatively detected by FDG-PET scan. Additionally, another patient was considered to have lymph node metastasis according to increased focal FDG uptake; however, all lymph nodes were free of malignant disease upon final pathology. In contrast, all other patients without lymph node metastasis upon final pathology showed negative preoperative FDG-PET scans. The meta-analysis yielded a sensitivity, specificity, PPV, NPV and accuracy of 0.53, 0.91, 0.57, 0.90 and 0.84, respectively. CONCLUSION: In patients with uterine corpus cancer, FDG-PET had an insufficient positive predictive value in detecting lymph node metastases, indicating that this method cannot replace surgical staging. However, due to its high NPV, FDG-PET might be beneficial in selected patients who are poor candidates for surgical staging.

Estrogen replacement therapy after endometrial cancer: a survey of physicians' prescribing practice.

OBJECTIVE: To determine whether the prescribing practice of physicians with regard to estrogen replacement therapy (ERT) in symptomatic women with previous endometrial cancer is consistent with the available evidence. METHODS: A descriptive survey was conducted among physicians in Germany, using a questionnaire containing two hypothetical cases of endometrial cancer patients ('low-risk' and 'high-risk' disease) and menopausal symptoms. Physicians were asked about their prescribing practice concerning moderate to severe menopausal symptoms. RESULTS: Four hundred and twenty questionnaires were sent out, with an overall response rate of 39.8%; 45.6% in the 'low-risk' case and 75.4% in the 'high-risk' case (p < 0.0001) stated that ERT is contraindicated. Only 12.9% were willing to prescribe ERT; 81.9% preferred to prescribe non-estrogenic alternatives (44.8% phytoestrogens, 29.0% selective serotonin reuptake inhibitors). CONCLUSION: Despite the evidence that ERT does not increase the risk of recurrence of endometrial cancer, many physicians are reluctant to prescribe ERT in women suffering from moderate to severe menopausal symptoms.

Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study.

BACKGROUND: Standard treatment of patients with breast cancer decreases with age and older persons are mostly excluded from clinical trials. We hypothesized that non-adherence to treatment guidelines occurs for women aged > or =70 years and changes overall survival (OAS) and disease-free survival (DFS). PATIENTS AND METHODS: We enrolled 1922 women aged > or =50 years with histologically confirmed invasive breast cancer treated at the University of Ulm from 1992 to 2005. Adherence to guidelines and effects on OAS and DFS for women aged > or =70 years was compared with that for younger women (50-69 years). RESULTS: Women >70 years less often received recommended breast-conserving therapy (70-79 years: 74%-83%; >79 years: 54%) than women aged < or =69 years (93%). Non-adherence to the guidelines on radiotherapy (<70 years: 9%; 70-79 years: 14%-27%; >79 years: 60%) and chemotherapy (<70 years: 33%; 70-79 years: 54%-77%; > 79 years: 98%) increased with age. Omission of radiotherapy significantly decreased OAS [< or =69 years: hazard ratio (HR) = 3.29; P <0.0001; > or =70 years: HR = 1.89; P = 0.0005] and DFS (< or =69 years: HR = 3.45; P <0.0001; > or =70 years: HR = 2.14; P <0.0001). OAS and DFS did not differ significantly for adherence to surgery, chemotherapy, or endocrine therapy. CONCLUSION: Our study confirms that substandard treatment increases considerably with age. Omission of radiotherapy had the greatest impact on OAS and DFS in the elderly population.

Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients.

Several adipocytokines, such as leptin or adiponectin, are associated with obesity and the risk for breast cancer. Adiopcyte fatty acid binding-protein(A-FABP) is another protein found in adipose tissue;therefore, we investigated the association of A-FABP with the occurrence and prognosis of breast cancer. In our study,200 women attending the University of Ulm for breast surgery between the years 2005 and 2007 were included;159 had histologically confirmed breast cancer; 41 had histologically confirmed benign lesions. Serum levels ofA-FABP, leptin, and adiponectin were measured, and their relationship to body-mass-index (BMI), breast cancer, and tumor characteristics were analyzed; logistic regression model was adjusted to age, BMI, menopausal status, use of Hormone Replacement Therapy (HRT), and family history of breast cancer. Serum A-FABP levels were found to be significantly higher in obese (BMI C 25) than in non-obese women (BMI B 24.9), 41.16 ng/ml and 24.95 ng/ml,respectively (P\0.0001). Independent of obesity, the serum A-FABP levels were significantly higher in breast cancer patients (34.65 ng/ml) than in healthy controls(24.47 ng/ml), P\0.0001; the odds ratio (1.038, P\0.05,95% confidence interval 1.001-1.72) showed a significant association of A-FABP with breast cancer risk. Serum leptin levels showed a strong correlation with BMI(rs = 0.78) and were significantly higher in breast cancer patients (20.87 ng/ml) than in controls (14.90 ng/ml),P\0.05. In contrast, adiponectin showed no significant association with breast cancer. Concerning tumor characteristics,A-FABP was positively connected with tumor size (T C 2 cm, P\0.05) and nodal-status (P\0.05).Our study reveals that high A-FABP serum levels are associated with obesity, breast cancer risk, and adverse tumor characteristics.

Growth hormone receptor mRNA expression in non-functioning and somatotroph pituitary adenomas: implications for growth hormone substitution therapy?

The use of growth hormone (GH) in patients with GH deficiency induced by pituitary adenoma is widely accepted, but the safety of this mitogenic hormone, particularly in patients with residual tumor after neurosurgery, continues to be a concern. Since the mitogenic potency of GH is dependent upon the presence of the GH receptor (GH-R) and the subsequent IGF-1/IGF receptor (IGF-1-R) system we investigated the expression of the members of the growth hormone cascade in endocrine inactive and GH-producing pituitary adenomas. Tissue specimens of 18 clinically non-functioning pituitary adenomas and 6 GH-producing adenomas were collected following transsphenoidal surgery while normal cadaver pituitary glands served as controls. After RNA extraction, semi-quantitative RT-PCR amplification with specific primers for GH, GH-R, IGF-1 and IGF-1-R was performed. Applying this sensitive RT-PCR based approach, GH-R expression was demonstrated in all normal pituitaries, most inactive adenomas (94%), and the majority of GH-producing adenomas (66%). Both IGF-1 and IGF-1-R mRNA was detectable in the majority of inactive (72% and 77%, respectively) and somatotrophic adenomas (83% and 83%). While IGF-1-R mRNA was expressed in all normal pituitary specimen studied, IGF-1 was detectable in only 55% of them. In summary, expression of members of the GH-IGF-1 cascade could be demonstrated in a substantial subset of patients with non-functioning and GH-producing pituitary adenomas. These factors might serve as a substrate for the transduction of mitogenic effects of GH on remnant pituitary tumors during GH replacement therapy. Therefore, GH therapy should be carefully considered and patients on GH therapy kept under close observation.