Fabienne Schochter

Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program

AbstractPurpose The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already been screened for CTC.MethodsWomen with HER2-negative primary tumor and presence of CTC are recruited into different DETECT trials according to the HER2-phenotype of CTC. Patients with HER2-positive CTC are randomized to treatment with physicians’ choice therapy (standard chemo- or endocrine therapy) with or without additional HER2-targeted therapy with lapatinib in the DETECT III trial. In DETECT IVa, postmenopausal patients with hormone-receptor positive primary cancer and HER2-negative CTC receive everolimus and standard endocrine therapy. For women with HER2-negative CTC and triple negative MBC or hormone-receptor positive tumor and indication for chemotherapy, a treatment with eribulin is offered (DETECT IVb). The clinical efficacy is investigated by CTC-Clearance and progression-free survival (PFS). The DETECT V/CHEVENDO trial extends the DETECT study program for women with HER2-positive and hormone-receptor positive MBC. The primary objective of this trial is to compare safety and quality of life (QoL) as assessed by the occurrence of adverse events in patients treated with dual (trastuzumab plus pertuzumab) HER2-targeted therapy plus either endocrine or chemotherapy. The translational research projects of the DETECT study program focus on further molecular characterization of CTC and evaluation of markers for their suitability to predict treatment response and to facilitate the development of more personalized treatment options.

Is open surgery the solution to avoid morcellation of uterine sarcomas? A systematic literature review on the effect of tumor morcellation and surgical techniques

PurposeToday’s surgical standard of care for uterine leiomyomas is laparoscopic and/or vaginal surgery with larger specimens requiring morcellation to avoid open surgery. This is often associated with intra-abdominal dissemination of cellular material which in case of a uterine sarcoma might result in iatrogenic seeding of malignant tumor cells. The aim of this systematic literature review is to evaluate the surgical techniques and the impact of accidental tumor morcellation on the outcome of patients postoperatively diagnosed with malignant uterine sarcomas.MethodsThe National Library of Medicine database (pubmed) and Web of science were searched individually using three different search terms (‘morcel* sarcoma’, ‘survival, sarcoma, treatment, Uter*’, and ‘disease free survival, sarcoma, treatment, uter*’). After excluding duplicates and screening for relevance, 16 articles were left for full-text review, resulting in seven case series with more than 5 patients.ResultsThe case numbers range from 14 to 123 patients with the majority of cases being leiomyosarcomas.ConclusionThere is no reliable diagnostic tool to differentiate a fibroid from a uterine sarcoma preoperatively. Tumor morcellation occurs in various open and closed surgical techniques and is not limited to laparoscopic surgery only. There is an urgent need for a presurgical diagnostic parameter.

Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?

Dissemination of tumour cells and the development of solid metastases occurs via blood vessels and lymphatics. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be detected in venous blood in patients with early and metastatic breast cancer, and their prognostic relevance has been demonstrated on numerous occasions. Repeated testing for CTCs and ctDNA, or regular so-called “liquid biopsy”, can be performed easily at any stage during the course of disease. Additional molecular analysis allows definition of tumour characteristics and heterogeneity that may be associated with treatment resistance. This in turn makes personalised, targeted treatments possible that may achieve both improved overall survival and quality of life.

Endocrine Treatment with 2 Years of Tamoxifen versus 2 Years of Exemestane in Postmenopausal Patients with High-Risk Early Breast Cancer and Persisting Circulating Tumor Cells - First Results of the SUCCESS C Endocrine Treatment Sub-Study

Background: Optimal choice and sequence of endocrine treatment following adjuvant chemotherapy in postmenopausal early breast cancer patients are still under discussion and treatment stratification factors are missing. Patients and Methods: Postmenopausal women with HER2-negative, hormone receptor-positive tumors and persisting circulating tumor cells (CTCs; assessed using the FDA-approved CellSearch® System, Janssen Diagnostics, LLC) after chemotherapy were randomized to 2 years of tamoxifen followed by 3 years of exemestane (tamoxifen-exemestane group, n = 54) or 5 years of exemestane (exemestane-only group, n = 54). CTCs were again assessed after the first 2 years of endocrine treatment. In addition, safety data were compared between the 2 groups. Results: The 2 groups were well-balanced with regard to baseline characteristics. The CTC clearance rate after 2 years was 89% in the exemestane-only group and 97% in the tamoxifen-exemestane group (exact Fisher test, p = 0.36). The safety profile showed good tolerability with few grade 3 or 4 adverse events in both groups. Conclusion: The similar CTC clearance rate after 2 years of endocrine therapy with exemestane or tamoxifen, and the safety profiles obtained may indicate comparable efficacy and tolerability of both endocrine treatment regimens. However, these results have to be confirmed by final survival and safety analysis.

Präinvasive Läsionen und Zervixkarzinom in der Schwangerschaft

ZusammenfassungIm Rahmen der üblichen Schwangerschaftsvorsorge erfolgt meist im ersten Trimenon eine gynäkologische Untersuchung mit Inspektion der Zervix und Entnahme eines zytologischen Abstrichs. Hierbei zeigt sich bei bis zu 7 % der schwangeren Frauen ein auffälliger zytologischer Befund. Bei 0,05 % der Schwangeren wird zudem die Diagnose eines Zervixkarzinoms gestellt, das nach dem Mammakarzinom die häufigste Neoplasie in der Schwangerschaft ist. Die weitere Abklärung und Therapie präinvasiver und invasiver Läsionen der Zervix ist in der Schwangerschaft meist erschwert, sodass sich die betroffene Frau häufig in einem – oft als extrem belastend wahrgenommenen – Konflikt zwischen der eigenen Gesundheit und dem Wohlergehen des Kindes befindet. Aus Ermangelung prospektiver Studien beruhen viele Empfehlungen auf retrospektiven Daten. Aufgrund der besonderen Situation in graviditate muss die Therapie somit häufig individuell an die Patientin und ihre Bedürfnisse angepasst werden. Daher soll im Beitrag eine Übersicht gegeben werden über die aktuellen Empfehlungen zu Diagnostik und Therapie der dysplastischen Veränderungen und Neoplasien der Zervix während der Schwangerschaft.AbstractA gynecological examination with inspection and cytological assessment (via pap smear) of the cervix is part of routine prenatal care in Germany and mostly performed in the first trimester. In up to 7% of pregnant women abnormal cytological findings of the cervix are diagnosed. In 0.05% of pregnant women invasive cervical cancer is also diagnosed, which is the second most frequent neoplasm in pregnancy after breast cancer. Further clarification and treatment of preinvasive and invasive cervical lesions are mostly difficult during pregnancy, so that affected patients find themselves in an often extremely stressful conflict situation between the well-being of the unborn child and their own health; however, due to a lack of prospective studies many recommendations on diagnostics and treatment of cervical cancer during pregnancy are based on retrospective data. Due to the special circumstances in pregnancy, therapeutic and diagnostic interventions therefore have to be individually adapted to each patient and their needs. This review article gives a summary of the current recommendations on the treatment and diagnostics of dysplastic alterations and invasive lesions of the cervix during pregnancy.

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer

Background Use of anthracycline‐based chemotherapy in patients with early breast cancer (EBC) has been well‐established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)‐negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline‐containing or anthracycline‐free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. Methods The SUCCESS C trial (NCT00847444) is an open‐label, phase III study randomizing 3547 patients with HER2‐negative EBC to either 3 cycles of epirubicin, 5‐fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC‐DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC‐C). CTC status was prospectively evaluated in hormone receptor‐positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration‐approved CellSearch System (Janssen Diagnostics). Results Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC‐DOC or DOC‐C (11.5% vs. 13.6%; P = .18). Conclusions The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline‐free chemotherapy is equally effective to anthracycline‐containing chemotherapy in HER2‐negative, hormone receptor‐positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings. Micro‐Abstract The prevalence of circulating tumor cells (CTCs) in patients with human epidermal growth factor receptor 2‐negative, hormone receptor‐positive early breast cancer after adjuvant chemotherapy was compared between anthracycline‐free and anthracycline‐containing treatment cohorts within the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C trial and showed no significant difference. Though CTCs have been established as an early treatment monitoring tool, comparison of CTC prevalence after therapy may have clinical implications with respect to equal effectiveness of both treatment regimens.

Hysterektomie – operative Innovationen in der Gynäkologie am Beispiel einer „alten“ Operation

ZusammenfassungDie Geschichte der Hysterektomie ist lang, und die Hysterektomie ist die weltweit am häufigsten durchgeführte gynäkologische Operation. Entsprechende operative Fähigkeiten und Methoden, ausgehend von klassischen Operationstechniken der vaginalen und der abdominellen Hysterektomie, haben im Laufe der Zeit enorme Weiterentwicklungen erfahren. Der vorliegende Beitrag zeichnet den geschichtlichen Werdegang der Hysterektomie nach, führt die heutigen Operationsverfahren der Hysterektomie bei benignen Erkrankungen auf und erläutert wichtige Aspekte bei der Wahl der heutigen Operationsverfahren.AbstractThe history of hysterectomy is long and hysterectomy is the most frequently performed gynecological operation worldwide. Appropriate operative capabilities and methods, based on classical operation techniques of vaginal and abdominal hysterectomy, have experienced an enormous further development during the course of time. This article reconstructs the historical development of hysterectomy, describes the current operative procedure of hysterectomy for benign diseases and illustrates important aspects in the selection of the currently used operative procedures.

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.

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. Micro‐Abstract The present study examined the association between granulocyte colony‐stimulating factor (G‐CSF) and prognostic markers cancer antigen (CA)27.29 and circulating tumor cells (CTCs) in 2646 early‐stage breast cancer patients. Those with G‐CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy than those without any G‐CSF application during chemotherapy, although no association with CTCs was found.

Erratum to: Current role of liquid biopsy in metastatic breast cancer and future perspectives

Gynäkologe 2016 · 49:970–972 DOI 10.1007/s00129-016-3970-6 Published online: 26 September 2016