The WID-qEC test: Performance in a hospital-based cohort and feasibility to detect endometrial and cervical cancers.

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.

Ki67 as Proliferative Marker in Patients with Early Breast Cancer and Its Association with Clinicopathological Factors.

INTRODUCTION: Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. MATERIAL AND METHODS: Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (n = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. RESULTS: 595 (64.9%) patients had a Ki67 <20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1-90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2-) disease (n = 717), 20% for HR+/HER2+ (n = 76), 30% for HR-/HER2+ (n = 45), and 60% for HR-/HER2- (n = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (<20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%). CONCLUSION: This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

Case Report and Review of the Literature of a Rare Entity of a Uterine Fibroid: A Genital Rhabdomyoma.

Extracardiac rhabdomyomas are rare benign tumors. According to histopathologic and clinical characteristics, they are divided into 3 subgroups: adult, fetal, and genital rhabdomyomas. Various adult extracardiac rhabdomyomas have been reported in the head and neck region, whereas genital rhabdomyomas are uncommon. Here, we report on a uterine genital rhabdomyoma in a 32-yr-old woman with secondary sterility. After myomectomy, the histopathologic analysis showed a slow cycling tumor with striated muscle differentiation and without any evidence of malignancy. Immunohistochemical staining proved coexpression of actin, caldesmon, and desmin. To the best of our knowledge, this is the first case of a uterine-based genital rhabdomyoma.

CT Scan in the Prediction of Lymph Node Involvement in Ovarian Cancer - a Retrospective Analysis of a Tertiary Gyneco-Oncological Unit.

Background The prognostic value of lymph node removal in ovarian cancer varies depending on the tumor stage. While in the advanced stage the removal of clinically normal lymph nodes does not improve the prognosis, this is still unclear in the early stages. Evaluation of the lymph nodes based on preoperative imaging influences the surgical procedure. Methods This retrospective analysis was performed by analyzing data from 114 patients with ovarian cancer, treated in our university hospital in the years 2000 - 2012. Diagnostic performance of imaging by computer tomography with respect to the correct prediction of lymph node status was analyzed in terms of sensitivity, specificity, positive predictive value and negative predictive value. Results Imaging by computer tomography showed a rather limited diagnostic performance with regard to the detection of lymph node metastases in ovarian cancer, with a sensitivity of 40.7%, a specificity of 89.1%, a positive predictive value of 80.0%, and a negative predictive value of 58.3%. A separate analysis for pelvic and paraaortic lymph node involvement showed a better diagnostic performance of computer tomography for the detection of positive paraaortic lymph nodes (41.2, 93.1, 84.0, and 64.3% for sensitivity, specificity, positive predictive value and negative predictive value, respectively) as compared to the detection of positive pelvic lymph nodes (25.6, 91.8, 62.5, and 69.8%). Conclusion The preoperative prediction of lymph node status by computer tomography is limited. A decision for or against lymphadenectomy should not be made solely on the basis of this approach.

Lymph Node Ratio Can Better Predict Prognosis than Absolute Number of Positive Lymph Nodes in Operable Cervical Carcinoma.

BACKGROUND: Nodal status is the most important prognostic factor in cervical cancer. However, further risk stratification in node positive cervical cancer patients is warranted for optimal therapeutic decisions. MATERIAL AND METHODS: Nodal positive patients (n = 86) were retrospectively stratified into two groups according to either number of positive nodes (>3 vs. 1-3) or lymph node ratio (LNR) (≥10 vs. <10% and >6.6 vs. ≤6.6%). Univariable log-rank tests and both univariable and adjusted multivariable Cox regression models were used to evaluate the association between number of positive nodes or LNR and disease-free survival (DFS) and overall survival (OS). RESULTS: LNR was significantly associated with worse DFS in adjusted multivariable analysis, both when categorized as ≥10 versus <10% (HR 2.25, 95% CI 1.06-4.76, p = 0.034) and when categorized as >6.6 versus ≤6.6% (HR 2.79, 95% CI 1.23-6.37, p = 0.015). However, we found no significant association between number of positive nodes or LNR and OS. DISCUSSION: In operable node-positive cervical cancer, both number of positive lymph nodes and LNR can be used for further risk stratification with regard to DFS but not OS.

Influence of the New FIGO Classification for Cervical Cancer on Patient Survival: A Retrospective Analysis of 265 Histologically Confirmed Cases with FIGO Stages IA to IIB.

OBJECTIVE: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. METHODS: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. RESULTS: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. CONCLUSION: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

OBJECTIVE: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. DESIGN: Genome-wide association study. SETTING: Not applicable. PATIENT(S): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. RESULT(S): The median age of the 1,168 women was 41 years (range 19-45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5' upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. CONCLUSION(S): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

Quality of life during and after adjuvant anthracycline-taxane-based chemotherapy with or without Gemcitabine in high-risk early breast cancer: results of the SUCCESS A trial.

PURPOSE: In high-risk early breast cancer, adjuvant taxane-Gemcitabine combinations result in a recurrence-free survival similar to single-agent taxanes. However, haematologic toxicities and need for dose reductions are more frequent in combinations. Which option ultimately provides a better quality of life (QoL) is unknown. We compared the QoL curves before, during, and up to one year after three cycles of Fluorouracil-epirubicin-cyclophosphamide followed by three cycles of Docetaxel-Gemcitabine or Docetaxel. METHODS: Overall, 3691 women with recent R0-resection of a primary epithelial breast cancer participated in the nationwide SUCCESS A clinical trial. The centres sent QoL questionnaires of the European Organisation for Research and Treatment of Cancer before and up to 15 months after randomisation to Docetaxel-Gemcitabine versus Docetaxel. Multilevel analysis by chemotherapy arm estimated the QoL time curves, questionnaire return, and dropout. RESULTS: The combination caused one-point higher global QoL (95% confidence ±1; p = 0.05) and 1.1 lower odds of adherence to the outcome (95% confidence 1.0-1.1; p = 0.23) than the monotherapy. In both groups, a 10-point decrease during therapy preceded a 16-point increase after chemotherapy (p < 0.001). The secondary QoL outcomes showed transient superiority of the combination at the end of chemotherapy. Discontinuation from chemotherapy and its reasons were equal in both groups. CONCLUSIONS: While patients perceive a one-point QoL difference as meaningless, a six-point increase is clinically relevant for them. That is, both regimens cause the same relevant long-term QoL improvement. With the similar recurrence-free survival, the lower toxicity, and the shorter chemotherapy duration in mind, taxanes without Gemcitabine are the preference. This challenges previous recommendations supporting combinations.

Differential prognostic relevance of patho-anatomical factors among different tumor-biological subsets of breast cancer: Results from the adjuvant SUCCESS A study.

OBJECTIVES: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood. MATERIAL AND METHODS: Here we re-evaluated the impact of tumor size, nodal stage and tumor subtype on disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) in a retrospective analysis using data from the adjuvant SUCCESS A trial. Subgroup analyses were conducted to assess whether the effect of tumor size and nodal stage on survival depended on tumor subtype. RESULTS: Increasing tumor size, higher nodal stage and triple negative breast cancer (TNBC) were associated with unfavorable prognosis (all p < 0.001). There was no significant interaction between tumor subtype and tumor size (p > 0.5 for all four survival endpoints), but we found significant interactions between tumor subtype and nodal stage (p < 0.05 for all four survival endpoints), with no differences in survival among tumor subtypes for patients with pN0 tumors (all p > 0.05) and pronounced differences in survival among tumor subtypes for patients with positive nodal stage (all p < 0.001). CONCLUSIONS: This analysis confirms tumor size, nodal stage and tumor subtype as independent prognostic factors in high-risk early breast cancer. Nodal-positive patients with TNBC had a considerably worse outcome compared to nodal-positive patients with another tumor subtype. This underlines the importance for early detection particularly for patients with TNBC. TRIAL REGISTRATION: EudraCT 2005-000490-21; ClinicalTrials.gov Identifier: NCT02181101.

Axillary Surgery in Breast Cancer Patients Treated with Breast-Conserving Surgery at German Breast Cancer Centers Within the Last 14 Years - Comparison of a University Center and a Community Hospital.

Background Guideline recommendations for axillary surgical approach in breast cancer (BC) treatment changed over the last decade. Methods Data from all invasive BC patients (n = 5344) treated with breast conserving surgery (BCS) at the breast cancer centers of the University Hospital Ulm (U-BCC) and the community hospital Dachau (D-BCC) were included into a retrospective analysis for assessing information on axillary surgery between 2003 and 2016 based on the documented cancer registry data. Results The average annual rate of sentinel node biopsy (SNB) was 85.5% and 87.2% in Ulm and Dachau, respectively. SNB was performed more precisely at the U-BCC with a median of 2.4 resected lymph nodes (LN) compared to a median of 3.2 resected LN in Dachau. Median number of resected LN for axillary lymph node dissection (ALNE) showed a statistically significant reduction over time in Ulm (r s = - 0.82; p < 0.001) and Dachau (r s = - 0.76; p = 0.002). The rate of secondary ALNE (after SNB; 2° ALNE) decreased significantly in U-BCC (r s = - 0.76; p = 0.002) while it remained stable in D-BCC. The influential publication of the Z0011 study in 2010 resulted in a significant reduction of secondary ALNE (24.1% preZ0011 and 14.4% postZ0011; p < 0.001) in Ulm. Conclusion Changes in axillary surgery over time can be seen in the annual statistics of the reviewed BCCs. With BCS, mostly SNB was performed and numbers of removed LN in ALNE have decreased. In the U-BCC, the rate of 2° ALNE dropped after the publication of the Z0011 data. The fact that no such decrease for 2° ALNE was found in D-BCC suggests that university hospitals implement new data and research results into clinical routine earlier than peripheral community hospitals.

Foetal Doppler Parameters as a Prognostic Marker Before Induction of Labour.

Introduction The value of foetal Doppler ultrasonography before induction of labour for prognostic assessment of the duration of labour and foetal outcome is presented. Patients and Methods Doppler ultrasound of the foetal middle cerebral artery (MCA) and of the umbilical artery (UA) was performed in addition to evaluation of the Bishop score in 49 women around the expected date of confinement (38 + 0 - 42 + 0 weeks of gestation) prior to planned pharmacological induction of labour. These parameters were studied using non-parametric statistical methods for associations with the duration of induction until delivery, the mode of delivery and foetal outcome. Results The resistance index (RI) of the MCA (rs = 0.547, p < 0.001), but not the RI of the UA (rs = - 0.055, p = 0.707) correlated positively with the duration of induction. Moreover, a negative correlation was found between the RI of the UA and the baby's arterial cord pH at birth (rs = - 0.287, p = 0.046). No differences in the RI of MCA or UA were found between babies born vaginally and those delivered by secondary section. Conclusion The present data show that Doppler measurement of the foetal MCA and UA before pharmacological induction of labour at term can be a further parameter for prognostic estimation of the duration and success of induction and of foetal outcome in addition to the established Bishop score.

Use of Granulocyte-colony Stimulating Factor During Chemotherapy and Its Association With CA27.29 and Circulating Tumor Cells-Results From the SUCCESS A Trial.

BACKGROUND: Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA)27.29 and circulating tumor cell (CTC) levels during therapy. PATIENTS AND METHODS: A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy. RESULTS: Overall, 1324 of the 2646 patients (50.0%) available for analysis had ≥ 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (χ2 = 30.6, df = 3; P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test; Z = -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (χ2 = 1.2, df = 3; P = .75). CONCLUSION: Cautious interpretation is needed regarding elevated levels of MUC-1-derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy.

Prevalence of circulating tumor cells in early breast cancer patients 2 and 5 years after adjuvant treatment.

PURPOSE: Several studies have provided evidence on the prognostic relevance of circulating tumor cells (CTCs) detected before and after chemotherapy regarding overall survival (OS) and progression-free survival (PFS) in early breast cancer (EBC). We provide data on the prevalence of CTCs 2 and 5 years after primary diagnosis in a cohort of patients with EBC. METHODS: The SUCCESS study is a multicenter, prospective, randomized trial comparing PFS in primary breast cancer patients undergoing one of two adjuvant chemotherapy regimens followed by 2 versus 5 years of treatment with zoledronate. CTCs from patients without signs of breast cancer recurrence were analyzed in peripheral blood using the FDA cleared CellSearch® System (Veridex, USA) 2 and 5 years after primary diagnosis. RESULTS: CTCs were detected at 2 and 5 years after primary diagnosis in 96 (16.7%) and 47 (8.2%) of the 574 patients, respectively. There were no associations between CTC status and patient and tumor characteristics or treatment regimens. In 442 (77.0%) patients, no CTCs were detected at either of the two time points, and in 11 patients (1.9%), CTCs were found at both 2 and 5 years after primary diagnosis. In 85 (14.8%) patients, CTCs were present 2 years after primary diagnosis but not after 5 years, while 36 (6.3%) patients had CTCs in their blood only at the 5-year follow-up. CONCLUSIONS: In patients with EBC, CTCs can be detected even 5 years after primary diagnosis without clinical signs of disease recurrence.

Influence of Prognostic Factors on Lymph Node Involvement in Endometrial Cancer: A Single-Center Experience.

OBJECTIVE: The requirement for and extent of lymphadenectomy in endometrial cancer is still controversial. Clinicopathological prognostic factors could be helpful to predict lymph node involvement and avoid therefore unnecessary lymphadenectomy. The aim of this study was to investigate which factors can predict lymph node involvement and how lymph node metastases are distributed in the pelvic and para-aortic regions. METHODS: This retrospective analysis was performed by analyzing data from patients with endometrial cancer treated with standard surgery and lymphadenectomy at the Department of Gynecology and Obstetrics of the University Hospital Ulm in 2000 to 2013. RESULTS: One hundred twenty-five patients received pelvic lymphadenectomy with a median of 25 removed nodes, and 111 patients additionally received para-aortic lymphadenectomy with a median of 12 removed nodes. Metastatic lymph nodes were found in 24.8% of the patients, and a multivariate logistic regression showed that lymphovascular space invasion, histological type, and tumor stage significantly and independently predicted lymph node involvement. Of the 111 patients with both pelvic and para-aortic lymphadenectomy, 18 (16.2%) patients had metastatic para-aortic nodes, and 3 (2.7%) patients had isolated positive para-aortic lymph nodes without involvement of pelvic lymph nodes. DISCUSSION: Lymphovascular space invasion, histological type, and tumor stage are significant predictors of lymph node involvement in endometrial cancer. In patients at high risk of nodal involvement, lymphadenectomy should be performed systematically up to the renal vein. Large and carefully designed prospective studies are needed to evaluate patient cohorts for which a complete lymphadenectomy provides a survival benefit. In the future, the increasing use of sentinel node biopsy may facilitate a more personalized treatment of patients with endometrial cancer.

Prognostic Impact of Weight Change During Adjuvant Chemotherapy in Patients With High-Risk Early Breast Cancer: Results From the ADEBAR Study.

BACKGROUND: In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial. PATIENTS AND METHODS: The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (≥ 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses. RESULTS: Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by ≥ 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067). CONCLUSION: Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS.

Hypotension due to spinal anesthesia influences fetal circulation in primary caesarean sections.

PURPOSE: Hypotension due to spinal anesthesia is a well-known side effect in pregnant women receiving caesarean section. Little is known about its impact on fetal blood circulation. METHODS: 40 women with uncomplicated singleton term pregnancies prepared for caesarean section were prospectively evaluated by Doppler sonography before and immediately after spinal anesthesia. RESULTS: In 90% of the women, blood pressure significantly decreased after spinal anesthesia and 42.5% of the patients suffered from severe hypotension. We found a significant negative correlation between maternal blood pressure change and the resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a significant positive correlation between maternal blood pressure and fetal middle cerebral artery. CONCLUSION: Healthy fetuses seem to compensate well in situations with decreased uteroplacental blood flow due to maternal hypotension measured by means of RI changes in the fetal umbilical and middle cerebral artery. This raises the question if growth-restricted and/or preterm fetuses are able to compensate similarly or if general anesthesia would be a method of choice.

CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.

Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be considered with caution.

Chirurgische Behandlung von Melanomen in der Schwangerschaft: eine praktische Anleitung.

Als ein Tumor, der primär eine chirurgische Behandlung erfordert, ist ein neu diagnostiziertes oder vorbestehendes Melanom in der Schwangerschaft eine klinische Rarität. In solchen Fällen steht der Chirurg vor der Herausforderung, ein geeignetes therapeutisches Vorgehen festlegen zu müssen. Auf der Grundlage unserer klinischen Erfahrung und einer Übersicht über die Literatur geben wir in der vorliegenden Arbeit eine Anleitung für das praktische Vorgehen bei dieser seltenen klinischen Konstellation. Unserer Erfahrung nach müssen schwangere Melanom-Patientinnen im Hinblick auf ihre therapeutischen Optionen ausführlich beraten werden. Naturgemäß setzen sie ihr ungeborenes Kind an die erste Stelle und zögern, der erforderlichen Operation zuzustimmen, obwohl bei ihnen eine möglicherweise lebensbedrohliche Erkrankung diagnostiziert worden ist. Daher ist es entscheidend, diese Patientinnen klar darüber zu informieren, dass, wie die vorliegenden medizinischen Erfahrungen zeigen, eine Schwangerschaft per se kein Grund ist, eine notwendige Melanom-Operation aufzuschieben. Jedoch müssen bei einigen Parametern wie den präoperativen Bildgebungsverfahren, der Positionierung auf dem Operationstisch, der Überwachung, Anästhesie und der perioperativen Medikation bestimmte Anpassungen vorgenommen werden, um der speziellen Situation Rechnung zu tragen.

Surgical treatment of melanoma in pregnancy: a practical guideline.

A tumor primarily requiring surgical treatment, newly diagnosed or preexisting melanoma during pregnancy is a clinical rarity. In such cases, the surgeon faces the challenge of having to decide on the appropriate therapeutic course of action. Based on our clinical experience and a review of the literature, we herein provide a guideline on how to practically deal with this rare clinical conundrum. In our experience, pregnant melanoma patients require thorough counseling with respect to their therapeutic options. They naturally tend to put their unborn child first, and are hesitant to consent to necessary surgery despite a potentially life-threatening diagnosis. It is therefore crucial to clearly inform these patients that - based on existing medical experience - pregnancy by itself is no reason to hold off on any type of necessary melanoma surgery. However, various parameters such as preoperative imaging procedures, positioning on the operating table, monitoring, anesthesia, and perioperative medication require certain adjustments in order to comply with this special situation.

Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review.

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.