Conditional Disease-Free and Overall Survival of 1,858 Young Women with Non-Metastatic Breast Cancer and with Participation in a Post-Therapeutic Rehab Programme according to Clinical Subtypes

BackgroundBreast cancer in young women is associated with unfavourable tumour biology and is the main cause of death in this group. Conditional survival analysis estimates survival rates under the pre-condition of already having survived a certain time.ObjectivesTo describe conditional disease-free and overall survival of female breast cancer patients according to clinical subtypes and age.MethodsThis study analyses information from 1,858 breast cancer patients aged between 21 and 54 years, who were taking part in a post-therapeutic rehab programme (time between diagnosis and rehab start: maximum 24, median 11 months). Mean follow-up time was 3.6 years. We describe biological, clinical and pathological features in regard to different age groups (<40 and ≥40 years) and report conditional 5-year survival rates for overall and disease-free survival, and Cox proportional hazard models.ResultsVery young and young patients differed in regard to hormone receptor negativity, tumour grade, lymphovascular invasion, and molecular subtypes. Young women bore triple-negative and HER2-like disease more frequently. Conditional 5-year overall survival did not differ substantially between women <40 and 40–54 years of age (95 vs. 96%). It was highest for women with cancer of the luminal A subtype (98%) and lowest for the triple-negative subtype (91%). Lymphangiosis was a significant predictor of death. Results for disease-free survival were comparable.ConclusionsConditional 5-year overall survival after non-metastatic breast cancer was as high as 95.5%, and disease-free survival was 85.2%. When controlling for time between diagnosis and rehab start, molecular subtypes influenced overall and disease-free survival prospects. When additionally controlling for clinical characteristics, this effect only remained stable for disease-free survival.     

I. Short Story of Theodor Kocher's Life and Relationship to the International Society of Surgery

With the aim of promoting progress in surgery through the friendly exchange of views and experience, the International Society of Surgery was founded in Brussels in 1902, thereby helping to overcome the narrow boundaries of that time's nationalism. At its first congress, the International Society of Surgery (ISS), otherwise known by its French name, Société Internationale de Chirurgie (SIC), already numbered 638 members, among them the most important surgeons from all over the world. Theodor Kocher (1841–1917) was the president of the first congress, held in Brussels in 1905, and was also responsible for the choice of topics. His presidential address clearly reflected the high aims the Society set for itself. Kocher's personal and professional authority, his surgical skill, which he liked so much to communicate to his colleagues, and his international thinking shaped the young Society. He remained on the international committee of the ISS until his death. Renowned surgeons from all over the globe traveled to Bern to see Kocher at work, among whom were many distinguished leaders of U.S. surgery. Thus Kocher's contribution had a great impact on the developing surgery, in particular in the United States. A short curriculum outlines the personality of this outstanding surgeon.     

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages. Received: 24 November 1999 / Accepted: 21 April 2000     

II. Vinzenz Czerny (1842–1915): Grand Seigneur of Oncologic Surgery—Life, Influence, and Work of the Second Congress President of the ISS/SIC

Vinzenz Czerny, chairman and professor of surgery in Freiburg im Breisgau and in Heidelberg, Germany, is the typical example of a prominent surgeon with an elegant technique, who was also a keen observer and scientist at the turn of the nineteenth into the early twentieth century. Starting his career in Vienna, Austria, he can be looked upon as the most important disciple of Theodor Billroth. Whereas Billroth may be regarded as the father of modern gastrointestinal surgery, Czerny can be considered the father of modern surgery for intestinal malignancies and multimodal treatment. The early history of visceral cancer therapy is linked with his career. He became a surgeon of the highest rank, with great clinical skill, rare judgment, and vision who contributed essentially to the development of modern surgery. From his early education he maintained a lifelong affection for the natural sciences and was an excellent physiologist and pathologist. During his professional life he successfully built up a well deserved reputation for general and cancer surgery and for the introduction of radio- and chemotherapy into the treatment of tumors. Czerny founded and chaired the first experimental Institute for Cancer Research in Germany. Two years later, in 1908, he presided at the 2nd Congress of the International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC) in Brussels, a congress that was almost entirely devoted to the etiology of visceral cancer and the progress and achievements of its treatment. Czerny left a clear legacy of opinion and methods on which the modern era of surgical cancer treatment is based.     

Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells.

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) (Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of non-irradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h (before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose- and time-dependent manner with cancer cells having a stronger impact at low doses.     

Large Scale Manufacturing of B43(Anti-CD19)-Genistein for Clinical Trials in Leukemia and Lymphoma

We have conjugated the murine monoclonal anti-CD 19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD 19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD 19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma.     

Influence of hydroxyethylcellulose on the drug release properties of theophylline pellets coated with Eudragit RS 30 D.

The objective of this study was to investigate the influence of a hydrophilic polymer, hydroxyethylcellulose (HEC), on the release properties of theophylline from pellets coated with Eudragit RS 30 D, and the physicochemical properties of Eudragit RS 30 D cast films. The release rate of theophylline from Eudragit RS 30 D coated pellets decreased during storage at 25 degrees C/60% RH due to the further coalescence of colloidal acrylic particles. In addition, water-vapor permeability and tensile strength of Eudragit RS 30 D cast film decreased after 1-month storage at 25 degrees C/60% RH. The presence of 10% hydroxyethylcellulose in the coating formulation was shown to stabilize the drug release rate from coated pellets, the water-vapor permeability and the tensile strength of free films. Atomic force microscopy and scanning electronic microscopy were used to demonstrate that the HEC was immiscible with Eudragit RS 30 D in the cast films. The stabilization effect of HEC was investigated and determined to be due to the formation of an incompatible phase between the latex particles which impaired further coalescence of the colloidal acrylic particles.