Peter Widschwendter

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.

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.

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.

Nachsorge und Rehabilitation nach gynäkologischen Malignomen und Mammakarzinom

ZusammenfassungIn den letzten Jahrzehnten ist die Prävalenz von Krebserkrankungen in Deutschland deutlich angestiegen, während die Mortalität bei vielen Entitäten gesunken ist. Dieser Trend führt zu einer wachsenden Anzahl an Patientinnen in der onkologischen Nachsorge. Während die Therapien heutzutage im Allgemeinen auf evidenzbasierten Maßnahmen beruhen, stützen sich die Empfehlungen zur Nachsorge mangels großer randomisierter Studien meist auf Konsensempfehlungen. Während ein Lokalrezidiv häufig kurativ behandelt werden kann, besteht nach Detektion von Fernmetastasen meist nur die Möglichkeit einer palliativen Therapie. Die Herausforderung besteht daher in der Verknüpfung sinnvoller medizinischer Maßnahmen zur Erkennung eines Rezidivs bzw. symptomatischer Fernmetastasen unter Berücksichtigung der Bedürfnisse und der Lebensqualität der Patientin. Der Artikel gibt einen Überblick über die aktuellen Empfehlungen zur Nachsorge von Patientinnen mit gynäkologischen Tumoren, einschließlich des Mammakarzinoms.AbstractIn Germany, the prevalence of malignancies has steadily increased over the past few decades, while the mortality of most malignancies has decreased. Taken together this leads to an increasing number of patients in follow-up care. While most of today’s guidelines on therapy and diagnosis are evidence based, we lack prospective studies investigating the impact of follow-up visits on survival parameters. There are several aspects to consider in the follow-up of cancer patients after primary treatment. Local recurrence can most often be treated with curative intention, while metastatic disease can most often only be treated in a palliative way. Therefore, besides detection of recurrent and symptomatic metastatic disease, one must also attend the physical and psychological sequels from cancer treatment for the patient. The following article gives an overview oft current recommendations on follow-up of patients after primary treatment for gynecologic malignancies and breast cancer.

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.

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 babyʼs 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.

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.

Diagnostik und Therapie des Endometriumkarzinoms

ZusammenfassungDas Endometriumkarzinom ist das häufigste Karzinom des weiblichen Genitaltraktes. Symptomatisch wird diese – häufiger bei postmenopausalen Frauen auftretende Erkrankung – hauptsächlich durch atypische vaginale Blutungen. Ein routinemäßiges Screening gibt es nicht. Die deutlich häufigeren, östrogenabhängigen Typ-I-Karzinome sind prognostisch günstig, während die Typ-II-Karzinome ein deutlich aggressiveres Verhalten aufweisen. Die primäre Therapie ist in der Regel die Operation (Hysterektomie, Salpingoophorektomie beidseits und ggf. die pelvine und paraaortale Lymphonodektomie bzw. die Reduktion der Tumorlast in fortgeschrittenen Stadien). Der Stellenwert der Strahlentherapie und Chemotherapie kommt insbesondere bei aggressiveren und fortgeschrittenen Konstellationen zum Tragen bzw. auch dann, wenn eine Operabilität aufgrund von Komorbiditäten nicht gegeben ist.AbstractEndometrial cancer is the most common cancer of the female genital tract worldwide. It first becomes symptomatic with abnormal uterine bleeding and is most common in postmenopausal women and with increasing age in premenopausal women. There is no recommendation for routine screening in asymptomatic women. While prognosis of type I (estrogen dependent) cancer is excellent, type II cancer shows a much more aggressive behavior. Primary therapy is as a rule surgical (hysterectomy, bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymphadenectomy and reduction of tumor size in advanced stages). Chemotherapy and radiotherapy are recommended for more aggressive tumors or advanced stages and when the patient is inoperable due to comorbidities.

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.