Jessica Salmen

The German SUCCESS C Study - The First European Lifestyle Study on Breast Cancer.

Cohort trials have shown evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients. The SUCCESS C study is the first European trial to evaluate the effect of an intensive lifestyle intervention program on disease-free survival in women with early breast cancer and to examine the predictive value of selected biomarker candidates. A total of 3,547 women with early-stage, Her2/neu-negative breast cancer will be included. The first randomization will compare disease-free survival in patients treated with either 3 cycles of FEC (epirubicine, fluorouracil, cyclophosphamide), followed by 3 cycles of docetaxel or 6 cycles of docetaxel-cyclophosphamide, and thus assess the role of anthracycline-free chemotherapy. The second randomization compares disease-free survival in patients with a body mass index of 24–40 kg/m2 receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. In addition, the study will evaluate the predictive role of cancer-associated and obesity-related biomarkers for the prediction of disease recurrence and survival. This SUCCESS C trial will provide valuable information on the effects of a lifestyle intervention program on the prognosis of early breast cancer patients.

Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer.

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m2) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m2) and 5-fluorouracil (500 mg/m2) on days 1 and 8 and cyclophosphamide (75 mg/m2) on days 1–14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.

Blasenmole und gestationsbedingte trophoblastäre Neoplasien

ZusammenfassungHintergrundTrophoblasttumoren stellen eine heterogene Gruppe von Tumoren dar. Zu dem Formenkreis zählen unter anderem die Partialmole, die komplette Blasenmole, die invasive Blasenmole, das Chorionkarzinom, der Plazentabett – Tumor und der epitheloide Trophoblasttumor. Die vier zuletzt genannten Krankheitsbilder gehören zu den gestationsbedingten trophoblastären Neoplasien (GTN).Ziel der ArbeitIn der vorliegenden Arbeit wird eine Übersicht über Symptome, Diagnostik und Therapie der Blasenmole und der GTN gegeben.Klinische SymptomeDie häufigsten klinischen Symptome sind die vaginale Blutung sowie eine deutlich erhöhte Konzentration an humanem Choriongonadotropin (HCG). Daneben kann ein intensiv wachsender Uterus zur Diagnosestellung führen. Seltener treten Beschwerden aufgrund einer bereits stattgefundenen Metastasierung auf.DiagnostikGoldstandard sind die Vaginalsonographie sowie die Bestimmung des HCG. Eine histologische Sicherung ist erforderlich. Bei der Diagnose einer GTN ist ein Staging zur Detektion von Metastasen erforderlich.TherapieDie Therapie der Wahl bei der partiellen oder kompletten Blasenmole ist die operative Intervention. Bevorzugt werden sollte die Saugkürettage, da sie mit der geringsten Perforationsgefahr einhergeht. Bei den gestationsbedingten trophoblastären Neoplasien richtet sich die Therapie nach dem Stadium der Erkrankung. Je nach Stadium wird eine Mono- oder eine Polychemotherapie verabreicht.FazitAuch wenn die Inzidenz der Trophoblasterkrankungen gering ist, kann diese Erkrankung mit einer relevanten maternalen Morbidität assoziiert sein. Aus diesem Grund ist eine frühzeitige Diagnosestellung und eine stadiengerechte Therapie von entscheidender Bedeutung für die Prognose.AbstractBackgroundTrophoblastic diseases including hydatidiform moles (complete or partial), choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor are a heterogeneous group of tumors also referred to as gestational trophoblastic neoplasia (GTN).Aim of this paperAn overview on the clinical manifestations, diagnostics and the current treatment of GTN is provided in this article.Clinical manifestationsThe most common clinical symptoms are vaginal bleeding or an enlarged uterus. Serum human chorionic gonadotropin (HCG) levels are elevated. In the rare case of metastases these symptoms can lead to the primary tumor.DiagnosticsUltrasound of the uterus in combination with determination of serum HCG levels is the gold standard for the diagnosis. Once a malignancy is suspected histological confirmation is necessary. If a GTN is diagnosed a screening for distant metastases is recommended.TherapyThe recommended therapy of hydatidiform moles is ultrasound-guided vacuum curettage. Depending on the stage of a GTN the treatment varies between single agent and polychemotherapy.ConclusionAlthough trophoblastic malignancies are rare tumors, maternal morbidity is considerable high. Early diagnosis and adequate stage-oriented therapy increase the prognosis for patients.

Chemotherapie in der Schwangerschaft

ZusammenfassungBei den meisten Patientinnen mit in der Schwangerschaft aufgetretenem Mammakarzinom ergibt sich die Indikation zu einer adjuvanten/neoadjuvanten Chemotherapie. Allerdings sollte erst nach Abschluss von Fertilisation, Implantation und Organogenese ab der 14. SSW mit der Verabreichung dieser zytostatischen Therapie begonnen werden. Ein früherer Beginn geht mit einem deutlich erhöhten Risiko für Aborte und Fehlbildungen einher. Anthrazykline und Taxane gehören zu den Substanzen, die im zweiten und dritten Trimenon verabreicht werden dürfen. Zwar deuten Daten auf eine sichere Applikation der in utero applizierten Chemotherapie mit diesen Substanzen hin, doch Langzeitfolgen für die Kinder, wie Kardiotoxizität, erhöhtes Auftreten von malignen Erkrankungen oder eingeschränkte Fertilität, sind noch detaillierter zu erfassen. Derzeit gibt es keine Empfehlung zur Verabreichung einer zielgerichteten Therapie in der Schwangerschaft.AbstractIn the majority of women diagnosed with breast cancer in pregnancy adjuvant or neoadjuvant chemotherapy is indicated. Administration of chemotherapy should not start before 14 weeks of gestation when fertilization, implantation and organogenesis have been completed. An earlier start with cytotoxic drugs results in a higher rate of miscarriage, fetal death and major malformations. The use of anthracyclines and taxanes is possible in the second and third trimester. These substances seem to have a good safety profile but there is a need for more data about the long-term outcome in children with prenatal exposure to chemotherapy, particularly about a higher risk for malignancies, sterility and cardiotoxicity. Trastuzumab is currently not recommended in any trimester during pregnancy.

Adjuvante endokrine Therapie beim frühen Mammakarzinom

Zwischen 75 und 80% der Mammakarzinome weisen eine positive ER(Östrogenrezeptor)und/oder PR(Progesteronrezeptor)-Expression auf und werden als hormonsensitiv bezeichnet. Aufgrund der Tatsache, dass alle diese luminalen Karzinome antihormonell behandelt werden sollten, ist die endokrineTherapiebis heute eine der wichtigsten Standardtherapien beim Mammakarzinom. Erste Erfahrungsbeschreibungen zur Wirksamkeit einer Hormonablation gehen auf George T. Beatson zurück, der eine junge Patientinmit metastasiertem Mammakarzinom im Jahre 1895 mittels Entfernung beider Ovarien über viele Jahre stabil halten konnte. Das erste, im Jahr 1967 von Harper und Walpole entdeckte, antihormonelleMedikament war Tamoxifen. Insgesamt ist vor allem in den letzten Jahren ein Trend zur Verlängerung der Therapiedauer zu verzeichnen. Ziel des vorliegenden Artikels ist eine Übersicht über die aktuellen Empfehlungen zur adjuvanten endokrinen Therapie beim primärenMammakarzinom.

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.