André Hennigs

Predictors of early poor aesthetic outcome after breast‐conserving surgery in patients with breast cancer: Initial results of a prospective cohort study at a single institution

Background and objectives The aim of this study was to explore features of patients reporting early poor aesthetic outcome after simple breast‐conserving surgery.

Which patients with sentinel node-positive breast cancer after breast conservation still receive completion axillary lymph node dissection in routine clinical practice?

PurposeIn the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, patients with 1 or 2 tumour-involved sentinel lymph nodes (SLNs) gained no benefit from completion axillary lymph dissection (cALND). We examined implementation of evidence from this trial into routine clinical management.MethodsData were included from patients diagnosed with primary breast cancer in German breast cancer units between 2008 and 2015 and analysed retrospectively from a prospective maintained database. Descriptive analyses assessed time-trend changes in axillary surgery. Factors associated with cALND in patients with 1 or 2 positive SLNs were identified using multivariable logistic regression analysis.ResultsOverall, 179 breast cancer units provided data for 188,909 patients, of whom 13,741 (7.3%) had pT1/2cN0M0 invasive breast cancer with 1 or 2 tumour-involved SLNs and underwent breast-conserving surgery and adjuvant radiotherapy. cALND use decreased from 94.6% in 2008 to 46.9% in 2015 (p < 0.001). In multivariable analyses, the following factors were associated with cALND: fewer removed SLNs; two tumour-affected SLNs; younger age; lower annual case volume per hospital; higher tumour grade and lymphovascular invasion. No statistically significant influence was detected for hormone receptor or HER2 status.ConclusionIn our cohort, 7.3% of patients with primary breast cancer met the ACOSOG Z0011 inclusion criteria and could potentially have been spared the morbidity of cALND. cALND tended to be performed in patients with a higher axillary tumour burden. This study shows a shift towards less extensive axillary surgery through rapid implementation of new clinical trial evidence into routine clinical practice.

Is Breast Surgery Necessary for Breast Carcinoma in Complete Remission Following Neoadjuvant Chemotherapy

The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.

Initial results of the FUSION-X-US prototype combining 3D automated breast ultrasound and digital breast tomosynthesis

PurposeTo determine the feasibility of a prototype device combining 3D-automated breast ultrasound (ABVS) and digital breast tomosynthesis in a single device to detect and characterize breast lesions.MethodsIn this prospective feasibility study, the FUSION-X-US prototype was used to perform digital breast tomosynthesis and ABVS in 23 patients with an indication for tomosynthesis based on current guidelines after clinical examination and standard imaging. The ABVS and tomosynthesis images of the prototype were interpreted separately by two blinded experts. The study compares the detection and BI-RADS® scores of breast lesions using only the tomosynthesis and ABVS data from the FUSION-X-US prototype to the results of the complete diagnostic workup.ResultsImage acquisition and processing by the prototype was fast and accurate, with some limitations in ultrasound coverage and image quality. In the diagnostic workup, 29 solid lesions (23 benign, including three cases with microcalcifications, and six malignant lesions) were identified. Using the prototype, all malignant lesions were detected and classified as malignant or suspicious by both investigators.ConclusionSolid breast lesions can be localized accurately and fast by the Fusion-X-US system. Technical improvements of the ultrasound image quality and ultrasound coverage are needed to further study this new device.Key PointsThe prototype combines tomosynthesis and automated 3D-ultrasound (ABVS) in one device.It allows accurate detection of malignant lesions, directly correlating tomosynthesis and ABVS data.The diagnostic evaluation of the prototype-acquired data was interpreter-independent.The prototype provides a time-efficient and technically reliable diagnostic procedure.The combination of tomosynthesis and ABVS is a promising diagnostic approach.

RESPONDER – diagnosis of pathological complete response by vacuum-assisted biopsy after neoadjuvant chemotherapy in breast Cancer - a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial

BackgroundNeoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery.MethodsThis study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%.DiscussionAs a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery.During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error).Trial registrationThe trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register (DRKS00011761) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017.

Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry

Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests. This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections. RT-qPCR was performed using a multiplex RT-qPCR kit for ESR1, PGR, ERBB2, and MKI67 and the reference genes B2M and CALM2. Subsequent measurement of tumor biomarker mRNA expression to detect conversion revealed significant decreases in ESR1 and PGR mRNA and MKI67 upregulation (all p < 0.001) in MT compared to PT of all tumor subtypes and ERBB2 upregulation in MT from triple-negative PT patients (p = 0.023). Furthermore, ERBB2 mRNA was upregulated in MT brain biopsies, particularly those from triple-negative PTs (p = 0.023). High concordance between RT-qPCR and IHC was observed for ER/ESR1 (81%(κ 0.51) in PT and 84%(κ 0.34) in MT, PR/PGR (70%(κ 0.10) in PT and 78% (κ −0.32) in MT), and for HER2/ERBB2 (100% in PT and 89% in MT). Discordance between mRNA biomarker assessments of PT and MT resulting from receptor conversion calls for dynamic monitoring of BC tumor biomarkers. Overall, RT-qPCR assessment of BC target genes and their mRNA expression is highly concordant with IHC protein analysis in both primary and metastatic tumor.Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests.This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections. RT-qPCR was performed using a multiplex RT-qPCR kit for ESR1, PGR, ERBB2, and MKI67 and the reference genes B2M and CALM2.Subsequent measurement of tumor biomarker mRNA expression to detect conversion revealed significant decreases in ESR1 and PGR mRNA and MKI67 upregulation (all p < 0.001) in MT compared to PT of all tumor subtypes and ERBB2 upregulation in MT from triple-negative PT patients (p = 0.023). Furthermore, ERBB2 mRNA was upregulated in MT brain biopsies, particularly those from triple-negative PTs (p = 0.023). High concordance between RT-qPCR and IHC was observed for ER/ESR1 (81%(κ 0.51) in PT and 84%(κ 0.34) in MT, PR/PGR (70%(κ 0.10) in PT and 78% (κ -0.32) in MT), and for HER2/ERBB2 (100% in PT and 89% in MT). Discordance between mRNA biomarker assessments of PT and MT resulting from receptor conversion calls for dynamic monitoring of BC tumor biomarkers. Overall, RT-qPCR assessment of BC target genes and their mRNA expression is highly concordant with IHC protein analysis in both primary and metastatic tumor.

Is Mastectomy Oncologically Safer than Breast-Conserving Treatment in Early Breast Cancer

Aim: To describe and discuss the evidence for oncological safety of different procedures in oncological breast surgery, i.e. breast-conserving treatment versus mastectomy. Methods: Literature review and discussion. Results: Oncological safety in breast cancer surgery has many dimensions. Breast-conserving treatment has been established as the standard surgical procedure for primary breast cancer and fits to the preferences of most breast cancer patients concerning oncological safety and aesthetic outcome. Conclusions: Breast-conserving treatment is safe. Nonetheless, the preferences of the individual patients in their consideration of breast conservation versus mastectomy should be integrated into routine treatment decisions.

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial

Purpose Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness. Patients and methods In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter. Results Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts. Conclusion We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

Examensvorbereitungskurs für die Zweite Ärztliche Prüfung im Fach Gynäkologie und Geburtshilfe – Ein Proof-of-Concept an der Universitätsfrauenklinik Heidelberg

Zielsetzung: Der Zweite Abschnitt der Arztlichen Prufung stellt hohe Anforderungen an die Examenskandidaten. Eine spezifische Vorbereitung mittels eines Examensvorbereitungskurses anhand der gepruften Schwerpunkte konnte die Studierenden dabei unterstutzen, das im Studium erworbene Wissen im Hinblick auf die Anforderungen des schriftlichen Examens zu fokussieren. Eine dahingehende Analyse muss vor allem die Fragen nach Praktikabilitat, Nutzen und Bedarf eines solchen Kurskonzeptes beantworten. Material und Methoden: An der Universitatsfrauenklinik Heidelberg wurde ein neu initiierter zweitagiger Examensvorbereitungskurs (ganztagig a 8 Stunden) durchgefuhrt, welcher die Wiederholung des gesamten examensrelevanten Wissens des Faches Gynakologie und Geburtshilfe und die gemeinsame Diskussion von ca. 120 Examens-Altfragen beinhaltete. Begleitet wurde der Kurs von Ein- und Ausgangstestaten zur Abschatzung des Lernfortschritts sowie einer umfangreichen Evaluation am Ende des Kurses. Ergebnisse: Insgesamt nahmen 101 Examenskandidaten der Medizinischen Fakultat Heidelberg am Ende des 5. Studienjahres an zwei durchgefuhrten Pilotkursen (Sommer 2014; Winter 2015) teil. Die Ein- und Ausgangstestate zeigten eine Verbesserung der im Mittel erreichten Anzahl richtig beantworteter Fragen von 14,9 auf 18,0 (max. 20; pre-post-difference 95%-CI: [2,21; 3,98], t-test: p < 0,001). Die Evaluation (n = 77) zeigte eine sehr hohe Zufriedenheit mit der Kurskonzeption mit einer durchschnittlichen Bewertung von 5,63 (2014) bzw. 5,44 (2015) [Likert-Skala 1 = „ausergewohnlich schlecht“; 6 = „ausergewohnlich gut“]. Zusammenfassung: Die Studie konnte zeigen, dass ein zweitagiger Kompaktkurs nicht nur praktikabel und effektiv ist, sondern auch von den Teilnehmern als sinnvolles Angebot fur die individuelle Prufungsvorbereitung angenommen wird. Dass ein ahnliches Kursangebot auch fur andere Facher gewunscht wird, weist darauf hin, dass das Konzept prinzipiell eine Lucke im universitaren Lehrangebot zu schliesen vermag.

Immuntherapien beim Mammakarzinom

Das humane Immunsystem kann Pathogene effektiv abwehren. Versagt es bei der Abwehr vonTumorzellen bzw. bei Patienten, die Tumoren entwickeln? Kann man das Immunsystem von ausen bei der Bekampfung von Krebs unterstutzen? Die Idee, Krebs mit immunologischen Methoden zu behandeln, ist nicht neu. Welche Entwicklungen sie bei der Therapie des Mammakarzinoms genommen hat, wird im Folgenden dargestellt.