Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers.

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.

Survival benefit of pelvic and paraaortic lymphadenectomy in high-grade endometrial carcinoma: a retrospective population-based cohort analysis.

OBJECTIVE: The standard therapy for high-grade endometrial cancer is surgery but the therapeutic effects of pelvic and paraaortic lymph node dissection (LND) are poorly investigated. In this study, we retrospectively evaluated overall survival, recurrence rates and recurrence-free survival among patients with high-grade type I and II endometrial carcinoma who underwent LND. METHODS: This study included 284 patients who are recorded in the German Tumor Centre Regensburg form 1998 to 2015 and were selected by cancer grading, the absence of secondary tumors, primary surgery including hysterectomy and available follow-up. 244 of the 284 patients in this cohort were unequivocally classified as R0 after resection. RESULTS: A significantly increased overall survival was observed for systematic LND of 25 or more paraaortic and pelvic lymph nodes versus patients who did not undergo such intervention (p < 0.001) or had elective LND of 1-24 lymph nodes both in univariable (p = 0.016) and multivariable (p = 0.014) analysis. A similar observation was made for recurrence-free survival of patients in the cohort who underwent complete tumor resection (R0). In addition, a reduced cumulative recurrence rate was observed for patients with systematic LND. CONCLUSIONS: Our study provides evidence that the systematic removal of 25 or more pelvic and paraaortic lymph nodes reduces the recurrence rate and that it is beneficial for the long-term overall and recurrence-free survival of patients with high-grade endometrial cancer.

Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women.

Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30 % over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50 % after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For this reason, when indicating and supporting endocrine adjuvant therapy, physicians must ensure that compliance will be good. To prevent recurrence in the long run, it is much more effective to prescribe a somewhat less effective therapy that will actually be carried out than to prescribe one that is theoretically more effective, but is not adhered to consistently.

[Documentation Time and Effort and Associated Resources for Patients with Primary Breast Cancer from Diagnosis to End of Follow-Up - Results of a Multicentre Validation]. / Dokumentationsaufwand und verbundene Ressourcen bei Patientinnen mit einem primären Mammakarzinom - von der Primärdiagnose bis zur Abschluss der Nachsorge - Ergebnisse der multizentrischen Erhebung.

INTRODUCTION: Tumour documentation is essential for quality assurance of oncological therapies and as a source of reliable information about the in- and outpatient care. The documentation effort and the associated resource consumption were analysed for the example of breast cancer. MATERIAL AND METHODS: The different steps in the care of patients with primary breast cancer in a standardised disease situation were defined from initial diagnosis to the end of the follow-up. After the pilot phase, a multicentre validation (n=7 centres) was performed with the support of the Federal Ministry of Health. The documentation time points were horizontally collected and analysed with regard to amount, duration and personnel expenses. RESULTS: 57% of the documentation costs are caused by the physicians. Regarding the different centres, documentation costs were calculated between € 352.82 and € 1 084.08 per patient from diagnosis to completion of aftercare. Non-certified centres had a reduced documentation effort and thus lower costs. CONCLUSIONS: The results demonstrate the need for a reduction of the documentation effort - particularly for physicians - the most expensive profession in the health system. A quality improvement is expected from the certification with its special requirements. In this context, there is a justified demand for an adequate remuneration of the documentation effort for certified centres. Furthermore, it is necessary to reduce the number of variables for quality assurance and to define them centrally. A comprehensive multi-disciplinary documentation should be achieved. Investments in a single data set and interface enhancements of existing documentation systems should be realised.

The Right Treatment for the Right Patient - Personalised Treatment of Breast Cancer.

The probability of healing breast cancer has been greatly improved in recent decades through the introduction and optimisation of multi-modal therapies and interdisciplinary treatments. Today, in addition to surgery or radiation, most patients receive a systemic treatment. To prevent excessive treatment, patients whose prognosis is so good that certain adjuvant therapies can be foregone or reduced must be identified. A lack of compliance with therapy, especially in the endocrine therapies stretching over years, is a further problem. As only treatments that are also carried out can improve chances of survival, efforts to improve compliance must be intensified. Studies show that lifestyle changes influence the efficiency of medication on the one hand, and on the other hand can also by themselves achieve a relevant improvement of the prognosis. Therefore, it is time not only to treat the tumour, but to also focus on the patient as a whole in therapeutic interventions.

Primary Therapy of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: Opinions of German Specialists to the 14th St. Gallen International Breast Cancer Conference 2015 (Vienna 2015).

For the first time, this year's St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but - for logistical reasons - in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this year's votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility.

Enriching semantic knowledge bases for opinion mining in big data applications.

This paper presents a novel method for contextualizing and enriching large semantic knowledge bases for opinion mining with a focus on Web intelligence platforms and other high-throughput big data applications. The method is not only applicable to traditional sentiment lexicons, but also to more comprehensive, multi-dimensional affective resources such as SenticNet. It comprises the following steps: (i) identify ambiguous sentiment terms, (ii) provide context information extracted from a domain-specific training corpus, and (iii) ground this contextual information to structured background knowledge sources such as ConceptNet and WordNet. A quantitative evaluation shows a significant improvement when using an enriched version of SenticNet for polarity classification. Crowdsourced gold standard data in conjunction with a qualitative evaluation sheds light on the strengths and weaknesses of the concept grounding, and on the quality of the enrichment process.

Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).

[Management of abnormal uterine bleeding]. / Ursachen und Therapie von uterinen Blutungsstörungen.

Bleeding disorders are one of the most frequent gynecological problems. The causes of bleeding disorders, and their frequency in particular, vary depending on the age of the woman affected. In premenopause and perimenopause, the most frequent causes are hormonal, in up to 90 % of cases, as well as organic changes in the uterus such as myomas, adenomyosis uteri, or endometrial polyps, in up to 70 % of cases. Coagulation defects cause increased bleeding, particularly in girls and young women, with no other recognizable cause. The treatment of bleeding disorders is causally based, although if the woman does not wish to have children, the therapeutic algorithm in many cases leads to similar symptomatic measures. The following therapeutic approaches, listed in order of increasing efficacy, are mainly used in the treatment of increased bleeding: gestagen, estrogen-gestagen combination, levonorgestrel (Mirena) and endometrial ablation or myoma enucleation, with comparable success rates, and finally hysterectomy. Embolization of the uterine artery in myomas or adenomyosis uteri, nonsteroidal anti-inflammatory drugs, and antifibrinolytic agents represent alternatives that may be useful in individual cases. The paper provides an overview of the various causes, useful diagnostic measures, and treatment options in uterine bleeding disorders.

[Suspicion for intraabdominal adhesions -- is open laparoscopy the gold standard?]. / Verdacht auf intraabdominelle Verwachsungen -- ist die offene Laparoskopie der Königsweg?

Laparoscopy is used for most surgical procedures in gynaecology. In general complications are rare. However, one of the most critical steps is the initial laparoscopic entry into the peritoneal cavity. According to the literature serious complications occur in approximately 1-2/1 000 cases. Whereas major vascular injuries are mainly recognised immediately, delayed recognition of bowel injuries is frequent. Complication rates of different entry procedures used in gynaecological laparoscopy are similar even in high risk patients (intraperitoneal adhesions, obesity). Utilising an open - instead a closed - entry (either by Veress needle or first trocar) technique or alternativ entry positions are suggested by some authors. This review presents data available in the literature and highlights that open laparoscopy is no gold standard.

[Vaginal foreign body -- cause for a rectovaginal fistula]. / Vaginaler Fremdkörper als Ursache einer rektovaginalen Fistel.

A case of 56-year-old patient is presented with the diagnosis "carcinoma of the cervix". She suffered from brown, bad smelling vaginal discharge since half a year without any pain. Three weeks before she had noticed a postmenopausal bleeding. At the examination under anaesthesia with cysto- and rectoscopy we saw a rectovaginal fistula. In the vagina a white plastic object was found which could not be removed. Some days later a hysterectomy with extraction of the foreign body (aerosol cap) was done and the fistula was treated together with the surgeons. There was no evidence of a carcinoma. The patient suffers from multiple sclerosis since 20 years. On asking she told us that the foreign body was in place since about two years. She was not willing to relate any other information.

[Ipsilateral breast tumor recurrence after conservative breast cancer surgery -- diagnosis and therapy]. / Lokalrezidive nach brusterhaltender Therapie des Mammakarzinoms -- Diagnostik und Therapie.

In spite of the fact that breast cancer is a systemic disease, local control plays an important role in its management. While surgical, radiotherapeutic and systemic therapy of primary breast cancer are performed according to widely accepted guidelines, the management of ipsilateral breast tumor relapse (IBTR) is still a matter of individualised concepts because of the lack of randomised studies. IBTR represents a significant medical problem, since the recurrence rate is 5-15 % after 5 years and 20-25 % after 10 years. Incidence is higher in younger patients, in tumors with an extensive intraductal component, positive tumor margins, axillary lymph node metastases, negative steroid hormone receptors and high proliferative activity. Distant metastases after IBTR occur more often if the interval between primary diagnosis and IBTR is short (e. g. less than 4 years). Diagnosis of IBTR include breast palpation, mammography and breast ultrasound. In addition breast MRI can be used to further differentiate between benign and malignant lesions after breast conservation. Standard therapy in this setting remains mastectomy. Breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Breast irradiation after secondary breast-conservation can be carried out in some cases. Some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. The heterogeneous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients.

Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions.

Dynamic enhanced magnetic resonance (MR) mammography and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) of the breast were directly compared preoperatively in suspicious breast lesions. Forty-two breast lesions in 40 patients were examined with a three-dimensional dynamic MR imaging series and FDG-PET. The MR and PET examinations were evaluated separately and the results were compared with the histological findings. The sensitivity and specificity of each method were calculated. The diagnostic value of both modalities as single diagnostic tool and in combination was investigated. Nineteen malignant and 23 benign breast lesions were proven histologically. Magnetic resonance mammography and FDG-PET showed a sensitivity of 89 and 63%, respectively. The specificity was 74 and 91%, respectively. The combination of both imaging methods decreased the not-required biopsies from 55 to 17%. Only one false-negative finding-a patient pre-treated with chemotherapy-was observed in both methods. The combination of MR mammography and FDG-PET can help to decrease biopsies of benign breast lesions. Because of their high cost, these modalities should only be used in problematic cases to either rule out or to demonstrate malignancy. The best diagnostic strategy is achieved using MR mammography first. If the diagnosis is still questionable, FDG-PET can be performed.

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

[Feather--data acquisition in gynaecology and obstetrics]. / Feather - Datenerfassung in der Gynäkologie und Geburtshilfe.

Nowadays many types of medical documentation are based on computer facilities. Unfortunately, this involves the considerable disadvantage that almost every single department and specialty has its own software programs, with the physician having to learn a whole range of different programs. In addition, data sometimes have to be entered twice - since although open interfaces are often available, the elaborate programming required to transfer data from outside programs makes the financial costs too high. Since 1995 the University's of Frankfurt am Main Department of Gynecology and Obstetrics has therefore developed a consistent program of its own under Windows NT for in-patient facilities, as well as for some outpatient services. The program does not aim to achieve everything that is technically possible, but focuses primarily on user requirements. In addition to the general requirements for medical documentation in gynecology and obstetrics, the program can also handle perinatal inquiries and gynecological quality control (QSmed [Qualitätssicherung in der Medizin] of the BQS [Bundesgeschäftsstelle Qualitätssicherung]).

Molecular classification of breast cancer patients by gene expression profiling.

For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of node-positive tumours (14 of 16). In this subgroup there was a disproportionate number of patients who had already developed distant metastases at the time of diagnosis (25% in this subgroup, compared with 5% among the rest of the samples). Taken together, the use of these differentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence.

Rates and causes of disagreement in interpretation of full-field digital mammography and film-screen mammography in a diagnostic setting.

OBJECTIVE: This study was performed to determine the rates and causes of disagreements in interpretation between full-field digital mammography and film-screen mammography in a diagnostic setting. SUBJECTS AND METHODS: Patients undergoing diagnostic mammography were invited to participate in the digital mammography study. Three views, selected by the radiologist interpreting the film-screen mammography, were obtained in both film-screen mammography and digital mammography. Radiologists independently assigned a Breast Imaging Reporting and Data System (BI-RADS) category to the film-screen mammography and the digital mammography images. The BI-RADS categories were grouped into the general categories of agreement, partial agreement, or disagreement. A third and different radiologist reviewed all cases of disagreement, reached a decision as to management, and determined the primary cause of disagreement. RESULTS: Six radiologists reviewed digital mammography and film-screen mammography diagnostic images in a total of 1147 breasts in 692 patients. Agreement between digital mammography and final film-screen mammography assessment was present in 937 breasts (82%), partial agreement in 159 (14%), and disagreement in 51 (4%), for a kappa value of 0.29. The primary causes of disagreement were differences in management approach of the radiologists (52%), information derived from sonography or additional film-screen mammograms (34%), and technical differences between the two mammographic techniques (10%). CONCLUSION: Significant disagreement between film-screen mammography and digital mammography affecting follow-up management was present in only 4% of breasts. The most frequent cause of disagreement in interpretation was a difference in management approach between radiologists (interobserver variability). This source of variability was larger than that due to differences in lesion visibility between film-screen mammography and digital mammography.