Cyclic and Hochschild homology of one relator algebras via the X complex of Cuntz and Quillen

In der vorliegenden Arbeit benutzen wir den Zugang von Cuntz und Quillen, um die zyklische Homologie von Algebren mit einer einzigen definierenden Relation (1-R-Algebren) zu untersuchen. Wir zeigen für solche Algebren, dass die I-adische Filtrierung des X-Komplexes der dazugehörenden gemischten freien Erweiterung eine spezielle Form hat. Wir folgern daraus, dass in Dimensionen größer als 3 die zyklische Homologie solcher Algebren einfach periodisch ist. Für vier konkrete Beispiele (die irrationale Drehungsalgebra, die Weyl Algebra, ihre Modifikation mit einem invertierbaren Erzeuger und die Algebra der Laurent Polynome in zwei Variablen) bestimmen wir mit Hilfe des X-Komplexes vollständig die zyklische und Hochschildsche Homologie. Wir zeigen auch, dass jede 1-R-Algebra eine freie Auflösung der Länge 2 besitzt, und schreiben solche Auflösungen für konkrete Beispiele auf. Schließlich konstruieren wir einen 2-Zusammenhang auf der irrationalen Drehungsalgebra

Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis

Background: Chemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients. Methods: Based on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients. Results: Median time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks. Overall higher RTDI was correlated with a shorter TTDP (log-rank p = 0.0525 for 85% RTDI cut-off). Proportional hazards assumption was violated, there was an early drop in the TTDP-curve for the high RTDI group. It was explained by the fact that patients with primary disease progression (PDP) do have a high RTDI per definition. Excluding those 114 patients with PDP the negative correlation between RTDI and TTDP vanished. However, non-PDP patients with RTDI-cut-off levels <85% showed a shorter OS than patients with higher RTDI levels (p = 0.0086). Conclusions: Optimizing RTDI above 85% appears to improve long-term outcome of MBC patients receiving first-line chemotherapy. Lowering RTDI had no negative influence on short term outcome like OR and TTDP

Clinical feasibility of (neo)adjuvant taxane-based chemotherapy in older patients: analysis of >4,500 patients from four German randomized breast cancer trials

Introduction Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients. Methods Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (60 years, between 60 and 64 years, and 64 years) with primary breast cancer received taxane-based chemotherapy. Results Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged 60 years to 65.5% in patients aged 64 years (P<0.001), and neutropenia increased from 46.9% to 57.4% (P<0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age. Conclusions The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo) adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens

Characterization of Hormone Receptor and HER2 Status in Breast Cancer Using Mass Spectrometry Imaging

Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers. In this study, the proteomic content of 1191 human breast cancer samples was characterized by mass spectrometry imaging and the epithelial regions were employed to train and test machine-learning models to characterize the individual receptor status and to classify TNBC. The classification models presented yielded high accuracies for estrogen and progesterone receptors and over 95% accuracy for classification of TNBC. Analysis of the molecular features revealed that vimentin overexpression is associated with TNBC, supported by immunohistochemistry validation, revealing a new potential target for diagnosis and treatment

Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto

Background: The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear. Methods: We analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy. Results: After a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease. In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3–4; HR 1.63, 95% CI 1.08–2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64–4.04, p &lt; 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32–3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89–7.64, p &lt; 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28–12.44, p &lt; 0.001). Conclusions: Especially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P &lt; 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR- or G3, and 17.8 % in ILC/HR-/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P &lt; 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P &lt; 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours