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The therapy of choice for breast cancer patients requiring adjuvant chemo- or radiotherapy is increasingly guided by the principle of weighing the individual effectiveness of the therapy against the associated side effects. This has only been made possible by the discovery and validation of modern biomarkers. In the last decades and in the last few years some biomarkers have been integrated in clinical practice and a number have been included in modern study concepts. The importance of biomarkers lies not merely in their prognostic value indicating the future course of disease but also in their use to predict patient response to therapy. Due to the many subgroups, mathematical models and computer-assisted analysis are increasingly being used to assess the prognostic information obtained from established clinical and histopathological factors. In addition to describing some recent computer programmes this overview will focus on established molecular markers which have already been extensively validated in clinical practice and on new molecular markers identified by genome-wide studies.Die Therapiewahl für die Mammakarzinompatientin in der adjuvanten Situation folgt immer mehr dem Prinzip, die individuelle Therapieeffektivität und die Nebenwirkungen gegeneinander abzuwägen. Die Entdeckung und Validierung moderner Biomarker ermöglicht erst dieses Vorgehen. In den letzten Jahrzehnten und insbesondere in den letzten Jahren konnten einige Biomarker in die klinische Praxis und in moderne Studienkonzepte integriert werden. Nicht nur der Vorhersage der Prognose kommt hierbei eine besondere Bedeutung zu, sondern auch der Vorhersage des Therapieansprechens durch Prädiktivfaktoren. Die Nutzung der prognostischen Information aus etablierten, klinischen und histopathologischen Faktoren erfolgt aufgrund der Vielzahl von Untergruppen mehr und mehr in Form von mathematischen Modellen und computergestützter Auswertung. Neben der Darstellung aktueller Programme soll in dieser Übersichtsarbeit des Weiteren der Fokus auf etablierten, molekularen Markern, die bereits eine umfassende klinische Validierung vorweisen können, und neuen molekularen Markern liegen, die durch genomweite Ansätze identifiziert wurden.

Background: We present a series of skin-sparing mastectomies (SSMs) with skin reduction and immediate breast reconstruction to treat large and ptotic breasts. The technique combines oncological mastectomy with immediate subpectoral implant placement as a single-step procedure. Methods: Data was collected from a prospective database from February 2009 to April 2011. A total of 24 patients with macromastia or pronounced ptosis fulfilled the criteria for skin-saving mastectomy. All operations were carried out as a single-step procedure with adaptation of the contralateral breast by reduction mastopexy. Results: A total of 27 SSMs were performed in 24 patients. The mean implant volume was 265 cm3. Immediate reconstruction of the nipple-areola complex was done in 22 patients. The cosmetic and functional results were assessed in all patients 6 months postoperatively; mean follow-up time was 13 months. Mean patient age was 49 years. The cosmetic result was assessed as “very good” or “good” by 22 patients; 2 patients graded the result as “unsatisfactory”. There was one local recurrence. Conclusion: Our results support the use of this technique as a safe oncoplastic procedure which is well tolerated by patients.

Purpose: Human papillomavirus (HPV)16 E6 and E7 oncoproteins that are required for cellular transformation represent candidate targets for HPV specific and major histocompatibility complex (MHC) class-I restricted CD8+ T-cell responses in patients with cervical cancer. In the present study, we identified HPV specific T-cells in different biological compartments (peripheral blood lymphocytes [PBL], tumor tissue, tumor-draining lymphnodes) using MHC-class I tetramers containing an appropriate HPV 16 E7 peptide. Material and Methods: FACS sorted (fluorescence activated cell sorting) CD8+T-cells isolated from healthy blood donors (n=10), patients with carcinoma in situ (n = 9) and invasive cervical cancer (n = 15) were obtained from PBL, tumor and pelvic nodes and evaluated for the presence of HPV 16 E7 specific effector CD3 + lymphocytes using the new tetramer technology. HPV DNA in tumor tissue was detected by PCR. All cervical cancer lesions could be identified as HPV 16 positive. PBL, tumor infiltrating lymphocytes (TIL), or T-cells from tumor-draining lymph nodes were isolated, gated on CD3 + CD8+T-cells as indicated and tested for the frequency of HPV 16 E7 using HLA-A2 tetramer complexes. All patients included showed an HLA-A2 haplotype. Results: 50% of healthy individuals, but less than 20% of patients (cervical intraepithelial neoplasia (CIN), invasive cancer) showed a specific cytotoxic CD8 + immune response to a defined HPV 16 E7 11-19 epitope (YMLDLQPET) in peripheral blood. HPV-reactive cytotoxic T-cells were detectable in tumor-draining lymph nodes in only one patient. Conclusions: The tetramer-sorting of CD8 + T-cells from different biological compartments in patients with HPV associated cancer lesions permits the determination of the target specificity of CD8 + effector T-cells without further need for in vitro manipulation. Furthermore, this new method helps to define the most appropriate target epitopes for novel vaccine designs.

Purpose: HER-2 blocking strategies, for instance with trastuzumab (Herceptin®), have been successfully used in therapy of breast cancer. To study molecular mechanisms and the efficiency of HER-2 blocking therapies we established a mouse tumor model that allows switching-off of HER-2 expression in tumor tissue. Material and Methods: NIH3T3 cells conditionally expressing HER-2 by the TET-OFF system (NIH3T3-HER-2 cells) were subcutaneously injected into the dorsal skin of nude mice. These cells allowed switching-off of HER-2 expression by exposure to anhydrotetracycline. We examined the influence of HER-2 down-regulation on tumor volume of subcutaneously growing tumors in nude mice. Tumor development was studied by magnetic resonance imaging. HER-2 expression was quantified by Western Blot analysis. Results: Eight to ten days after injection of 7 × 10 6 NIH3T3-HER-2 cells small subcutaneously growing tumors became visible. A surprisingly efficient tumor remission was observed already 7 days after switching-off of HER-2 expression: mice with initial tumor volumes of 0.8, 1.2, 3.9 and 14.9 cm 3 showed a decrease in tumor volumes to 1.9, 11.8, 11.3 and 25.8%, respectively, compared to the respective volumes before anhydrotetracycline administration. In contrast, a steady increase in tumor volume was observed for mice not exposed to anhydrotetracyclin. Conclusion: Switching-off of HER-2 expression causes a strong remission already after 7 days. Interestingly, the extent of tumor remission depends on initial tumor size, whereby a stronger remission can be achieved for smaller tumors. Our data support clinical studies testing HER-2 blocking strategies as adjuvant therapy for early breast cancer.

Objective: To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs with respect to qualitative improvements of medical care before and after surgery. Methods: Between June 1993 and July 2003 129 women with cervical cancer were assessed before and 4 and 12 months after surgery by semistructured interviews and standardised questionnaires. Thanks to funding, since 1999 all patients with a diagnosis of genital or breast cancer can participate in this prospective study. In this paper we will focus on therapy-related changes in quality of life and body image in women with cervical cancer. The evaluation of quality of life (CARES) incorporated five aspects: physical and psychosocial health; marital and sexual status; medical interaction. With respect to body image (Strauss and Appelt) the attractiveness/self-confidence and sexual uncertainty were evaluated. Results: Before surgery, women with a Wertheim's procedure had significantly less problems with regard to the quality of life global score (p = 0.002) and several subscales compared to women with a pelvic exenteration. After surgery, both groups indicated that sexual problems were the greatest limitation in terms of quality of life, especially in women with non-reconstructive surgery as well as in women with adjuvant radio- and/or chemotherapy. With respect to body image, attractiveness/self-confidence was significantly reduced postoperatively compared to the preoperative status in both groups (p = 0.000), and also worsened with the extent of treatment. Conclusion: This on-going study demonstrates the interrelationship between the treatment and the patient's quality of life, especially with regard to sexuality and body image. Our results suggest not only providing reconstructive surgery if possible, but also integrating psychosocial information on future quality of life before surgery as well as offering psychosocial support related to the extent of treatment after surgery.

Purpose: Metallothioneins (MT) are small cysteine-rich proteins. Together with glutathione (GSH) they constitute the major fractions of intracellular thiols. Since MT as well as GSH have been reported to protect tumor cells from anti-neoplastic agents both thiols may play a role in drug resistance. In the present study, MT and GSH expression was determined in primary epithelial ovarian carcinomas and a possible association with histopathological parameters and survival time (differentiating between patients with and without standard chemotherapy) was examined. Material and Methods: Glutathione expression as well as expression of MT isoforms (MT-1 and MT-2) was determined in 151 patients suffering from primary epithelial ovarian cancer. Results: No association between MT or GSH expression and survival was observed in patients that received platinum-based chemotherapy. However, an interesting result was obtained by combined analysis of MT and total GSH content. The product of MT and GSH was negatively associated with survival of grade 1 carcinomas (p = 0.021, log-rank test). When MT x GSH was greater than the median 25% of patients with grade 1 carcinomas died within 235 days. In contrast, all patients with grade 1 carcinomas survived when MT x GSH in tumor tissue was smaller than the median. No influence of MT, GSH or MT x GSH on survival was observed for patients with grade 2 or grade 3 carcinomas. This szenario suggests that high expression of MT and GSH give a growth and/or selection advantage to grade 1 carcinomas, wheras other factors seem to be responsible for progression of grade 2 and 3 carcinomas. Conclusion: High expression of both sulfhydryl factors MT and GSH may identify a subgroup of low-grade carcinomas with an increased risk of progression.

We report a case of malignant rhabdoid tumour of the vulva occurring in a 31 year-old woman. Clinically, the lesion was misinterpreted as a Bartholin's cyst. After histological confirmation of malignancy, a radical excision of the tumour with an extended regional lymphadenectomy was performed. Histologically, the neoplasm was originally misdiagnosed as the neoplasm was originally histologically misdiagnosed as a leiomyosarcoma. Immunohistochemical and electron microscopic studies were required for a definite histological diagnosis. Rhabdoid tumour is unusual, and most often presents as a highly aggressive renal tumour in children. Rare examples of extrarenal rhabdoid tumours of identical morphology, and with an equally adverse prognosis have been reported in young adults. There is an ongoing debate as to whether rhabdoid tumours represent a separate tumour entity, or rather a phenotype which may be acquired by various malignant lesions. To date, five rhabdoid tumours of the vulva, with a fatal outcome in three cases, have been reported in the world literature. In the present case, a local recurrence had to be removed only six months after initial radical surgery.

Aim: Around half of all women in Germany with breast cancer are older than 65 and approximately one third of them is older than 70 years of age. In theory, the preferred therapeutic management of women with breast cancer aged 65 and above corresponds to that formulated for younger patients and complies with the S3 Guidelines and the therapy recommendations formulated by AGO. To study the current therapies used to treat women with breast cancer aged 70 and above in Germany, a survey of the clinics of the German Breast Group (GBG) was done. Method: An online survey was carried out with requests sent to 599 physicians registered as principal investigators in the database of the GBG. The 12-item questionnaire was used to investigate the systematic therapeutic management of 70-year-old patients in different settings. The indication for chemotherapy was taken as a given. Results: In a neoadjuvant setting, 62 % of physicians opted for anthracycline and taxane-based therapy as did 56.6 % of physicians in an adjuvant setting. One third of physicians preferred a taxane-based therapy with the anti-angiogenesis inhibitor bevacizumab as first-line therapy for primary metastatic cancer and after anthracycline-based therapy. Capecitabine (around 30 %) and navelbine (around 20 %) were proposed as second-line neoadjuvant and adjuvant therapies after prior anthracycline- and taxane-based therapy. Conclusion: The chemotherapy regimen prescribed for women with breast cancer aged 70 and above in Germany appears to be relatively standardised and corresponds to the recommendations given in the S3 Guidelines and by the AGO Breast Committee.