Breast cancer: are long-term and intermittent endocrine therapies equally effective?

PURPOSE In breast cancer (BC), the duration of endocrine adjuvant therapies (AT) has been extended continuously up to 10~years. We present an alternative explanation for the effect, which could enable shorter treatments. METHOD The relevant literature on chemoprevention and (neo-)adjuvant therapy was reviewed. Data for initiation and growth of primary and contralateral BCs and their metastases (MET) were considered. Also, population-based data from the Munich Cancer Registry for MET-free survival, time trends of MET patterns, and survival achieved by improved ATs are used to estimate all events in the long-term follow-up. RESULTS Extended ATs (EAT) that continue after 1, 2, or 5~years reduce mortality only slightly. The effect is delayed, occurring more than 5~years after extension. EATs does not affect the prognosis of 1stBCs, they preventively eradicate contralateral 2ndBCs and thus their future life-threatening METs. Because chemoprevention can eradicate BCs from the smallest clusters to almost detectable BCs, ATs can be temporarily suspended without imposing harm. Results equal to EATs can be achieved by short-term ATs of the 1stBC and by repeated neo-ATs targeted at the indefinitely developing 2ndBCs. Considering this potential in de-escalation, a 70-80% reduction of overtreatment seems possible. CONCLUSION Knowledge of initiation and growth of tumors with known effects of neo-ATs suggest that intermittent endocrine ATs may achieve the same results as EATs but with improved quality of life and survival because of fewer side effects and better compliance. The challenge for developments of repeated ATs becomes: how short is short enough

Changes in prognostic and therapeutic parameters in prostate cancer from an epidemiological view over 20 years

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The study objective was to examine changes in prognosis and treatment of prostate cancer patients over 20 years and to evaluate their impact on survival. &lt;b&gt;&lt;i&gt;Patients and Methods:&lt;/i&gt;&lt;/b&gt; 38,861 prostate cancer patients diagnosed between 1990 and 2010 and living in the catchment area of the Munich Cancer Registry were analysed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Pre-therapeutic prostate-specific antigen (PSA) testing increased substantially in the early 1990s. A shift from capsule-exceeding tumours to capsule-limited tumours also took place especially in the 1990s. The proportion of radical prostatectomy increased continuously over the last 20 years from 20% to almost 50% whereas hormone therapy decreased from 55% to 18%. Radiation therapy and transurethral resection of the prostate increased slightly from about 5% to 10%. The 5- and 10-year relative survival rates increased from 92% to 97% and from 86% to 92%, respectively. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; 2 reasons may account for the rise in survival rates over 20 years: First, the establishment of widely used PSA testing resulted in a shift towards more favourable T categories due to the detection of many additional small tumours as well as the noticeable change in initial treatment strategy towards more radical prostatectomies. The second factor that likely increased survival was improvements in the therapies themselves.</jats:p

Colonoscopy and polypectomy: beside age, size of polyps main factor for long-term risk of colorectal cancer in a screening population

PURPOSE Despite national and international guideline recommendations, few studies have been conducted to estimate the impact of colonoscopy screening on long-term colorectal cancer incidence. Aim of this study was to determine the long-term impact of a full colonoscopy with polypectomy on colorectal cancer incidence in a large screening population. METHODS In this prospective observational cohort study, a total of 10,947 colonoscopy screening participants from within the scope of the Munich Cancer Registry were consecutively recruited from participating gastroenterology practices and their subsequent colorectal cancer incidence assessed. Predictive factors associated with colorectal cancer were also evaluated in univariate and multivariate analyses. RESULTS After a median follow-up of 14.24~years (95% CI 14.21-14.25), 93 colorectal cancer cases were observed. This is equivalent to a truncated age-standardized rate of 69.0 (95{\%} CI 43.3-94.7) for male and 43.4 (95{\%} CI 29.4-57.5) for female participants ($\geq$ 50~years at colonoscopy). The ratio of this observed to the expected rate from cancer registry data showed a 67{\%} decrease in colorectal cancer incidence in the male and 65{\%} in the female participants (p {\textless} 0.0001). In multivariate analysis of screening patients, age at screening (p {\textless} 0.0001) was the main predictive factor for colorectal cancer. In the subgroup with positive polyp findings, age (p {\textless} 0.0001) and the polyp size (p = 0.0002) were associated with colorectal cancer. CONCLUSION These results underline the significance of a full colonoscopy screening combined with polypectomy in reducing the total disease burden of colorectal cancer

Risk of contralateral second primary breast cancer according to hormone receptor status in Germany

Introduction: Hormone receptor (HR) status has become an established target in treatment strategies of breast cancer. Population-based estimates of contralateral breast cancer (CBC) incidence by HR subtype in particular are limited. The aim of this study was to provide detailed data on CBC incidence for Germany. Methods: Invasive breast cancer data were extracted on 49,804 women yielding 594 second primaries from the cancer registries of the Federal States of Brandenburg and Saarland and the area of Munich for the period from 1998 to 2007. Multiple imputation was used on missing values for HR status. We estimated standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Results: SIR estimates of CBC among women diagnosed with an invasive first primary breast cancer (FBC) of any HR subtype ranged from 1.0 to 1.5 in the three registries. Pooling three registries' data, the SIR of HR-positive CBC was 0.7 (95% CI: 0.6 to 0.8) among women with HR-positive FBC. For those women with HR-negative FBC, the SIR of HR-negative CBC was 8.9 (95% CI: 7.1 to 11.1). Among women with FBC diagnosed before the age of 50 years, incidence of CBC was increased, especially for HR-negative FBC (SIR: 9.2; 95% CI: 7.1 to 11.9). Conclusions: HR status of the first primary and age at first diagnosis is relevant for predicting risk of CBC. Particularly, patients with HR-negative FBC had elevated risks

Risk of contralateral second primary breast cancer according to hormone receptor status in Germany

Introduction: Hormone receptor (HR) status has become an established target in treatment strategies of breast cancer. Population-based estimates of contralateral breast cancer (CBC) incidence by HR subtype in particular are limited. The aim of this study was to provide detailed data on CBC incidence for Germany. Methods: Invasive breast cancer data were extracted on 49,804 women yielding 594 second primaries from the cancer registries of the Federal States of Brandenburg and Saarland and the area of Munich for the period from 1998 to 2007. Multiple imputation was used on missing values for HR status. We estimated standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Results: SIR estimates of CBC among women diagnosed with an invasive first primary breast cancer (FBC) of any HR subtype ranged from 1.0 to 1.5 in the three registries. Pooling three registries' data, the SIR of HR-positive CBC was 0.7 (95% CI: 0.6 to 0.8) among women with HR-positive FBC. For those women with HR-negative FBC, the SIR of HR-negative CBC was 8.9 (95% CI: 7.1 to 11.1). Among women with FBC diagnosed before the age of 50 years, incidence of CBC was increased, especially for HR-negative FBC (SIR: 9.2; 95% CI: 7.1 to 11.9). Conclusions: HR status of the first primary and age at first diagnosis is relevant for predicting risk of CBC. Particularly, patients with HR-negative FBC had elevated risks

Distinct expression patterns of VEGFR 1-3 in gastroenteropancreatic neuroendocrine neoplasms: supporting clinical relevance, but not a prognostic factor

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are an increasing tumor entity. Since many patients are diagnosed at an advanced stage, treatment is still challenging and dependent on many tumor and patient specific factors. Therefore, the aim of the present study was to elucidate the expression rates and the prognostic value of vascular endothelial growth factor receptor (VEGFR) 1-3 in GEP-NENs. A potential association to immune checkpoint markers was further investigated. Material and Methods: The expression levels of VEGFR 1-3 were analyzed by immunohistochemistry and correlated with the expression of the checkpoint markers PD-1 and PD-L1. Furthermore, the tumor samples of 249 GEP-NEN patients were studied and correlated with overall survival rates and clinicopathological features. Kaplan–Meier analyses and the log rank test were used for survival analyses. Categorical variables were compared by the χ2 test. Results: The most common primary tumor site was the small intestine (50.6%), followed by the pancreas (25.7%). VEGFR 1 was highly expressed in 59%, VEGFR 2 in 6.4%, and VEGFR 3 in 61.8% of the analyzed samples. The expression of VEGFR 1-3 was not significantly associated with survival rates. Pancreatic NENs had the highest expression of VEGFR 1 and 3 in 80% of the cases. VEGFR 1-3 positivity correlated with the expression levels of immune checkpoint markers. Discussion: VEGFR 1-3 show a distinct expression pattern in different subgroups of neuroendocrine neoplasias indicating a conceivable target. Moreover, there was a substantial association between VEGFRs andimmune checkpoint markers. Taken together, anti-VEGFR therapy represents a promising therapeutic approach in GEP-NEN patients and should be addressed in future studies

Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma

(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS

Use of Multicenter Data in a Large Cancer Registry for Evaluation of Outcome and Implementation of Novel Concepts

Large clinical cancer registries (CCRs) in Germany shall be strengthened by the German Social Code Book V (SGB V) and implemented until the end of 2017. There are currently several large cancer registries that support clinical data for outcome analysis and knowledge acquisition. The various examples of the Munich Cancer Registry outlined in this paper present many-sided possibilities using and analyzing registry data. The main objective of population-based cancer registration within a defined area and the performance of outcomes research is to provide feedback regarding the results to the broad public, the reporting doctors, and the scientific community. These tasks determine principles of operation and data usage by CCRs. Each clinical department delivers its own findings and applied therapy. The compilation of these data in CCRs provides information on patient progress through the regional network of medical care and delivers meaningful information on the course of oncological diseases. Successful implementation of CCRs allows for presenting the statistical outcomes of health-care delivery, improving the quality of care within the region, accelerating the process of implementing innovative therapies, and generating new hypotheses as a stimulus for research activities

Patients with colorectal cancer and brain metastasis: The relevance of extracranial metastatic patterns predicting time intervals to first occurrence of intracranial metastasis and survival

To investigate the predictive impact of extracranial metastatic patterns on course of disease and survival in patients with colorectal cancer (CRC) and brain metastasis (BM). A total of 228 patients (134 male [59%], 94 female [41%]) with histologically proven CRC and BM were classified into different groups according to extracranial metastatic patterns. Time intervals to metastatic events and survival times from initial CRC diagnosis, extracranial and intracranial metastasis were analyzed. Extracranial organs mostly affected were liver (102 of 228 [44.7%]) and lung (96 of 228 [42.1%]). Liver and lung metastasis were detected in 31 patients (13.6%). Calculated over the entire course of disease, patients with lung metastasis showed longer OS than patients with liver metastasis or patients without lung metastasis (43.9 vs. 34.6 [p=0.002] vs. 35.0 months [p=0.002]). From the date of initial CRC diagnosis, lung metastasis occurred later in CRC history than liver metastasis (24.3 vs. 7.5 months). Once lung metastasis was diagnosed BM occurred faster than in patients with liver metastasis (15.8 vs. 26.0 months; Δ 10.2 months). Accordingly, OS from the diagnosis of liver metastasis was longer than from lung metastasis (27.1 vs. 19.6 months [p=0.08]). Once BM was present patients with lung metastasis lived longer than patients with liver metastasis (3.8 vs. 1.1 months [p=0.028]). Shortest survival times in all survival categories analyzed revealed patients with concurrent liver and lung metastasis. Patients with CRC and BM form a heterogenous cohort where EM to liver or lung predict survival

Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P <.001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.Peer reviewe