Data on development of the Wistar rat skeleton at the end of gestation.

Data presented gives detailed information on bone development and ossification grade of Wistar rat fetuses close to parturition (Gestation days 21-23). Focus lies on the representation of the ossification status of an individual and options to summarize the data without loss of information. Moreover the body weight development and food consumption data of the dams and non-pregnant females is included. For further interpretation please refer to the related article "The ossification status of Wistar rat fetuses at the end of gestation" (1).

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study.

BACKGROUND: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. METHODS: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. RESULTS: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. CONCLUSIONS: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. TRIAL REGISTRATION: Clinical Trials Number: CFEM345DDE19.

The ossification status of Wistar rat fetuses at the end of gestation.

We present a comprehensive description of spontaneous skeletal development of Wistar rat fetuses close to parturition. Fetuses were collected on the day of expected parturition and one and two days before (Gestation Days 21-23) and skeletal development state was examined. Data is presented on an individual fetal basis to allow insights in developmental patterns. The distal parts of the limbs and the cervical and caudal vertebral column were identified as areas of the greatest developmental difference in the examined time frame. Extensive knowledge of the ossification process in individual fetuses allows a better resolution of deviations from normal and gives valuable information for the grading of delayed maturation and structural deviations. The data base is helpful to overcome the bottleneck of coincident occurrence of low incidences of skeletal abnormalities in the dose groups and the control group complicating risk assessment of test articles.

Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the Munich Cancer Registry.

PURPOSE: Systemic therapies (ATHs) in early breast cancer have improved the survival of breast cancer (BC) patients in recent decades. The magnitude of the changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and in the metastasis (MET) pattern will be described. PATIENT AND METHODS: We analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and 11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients will be divided into four time periods to identify relationships between BC and METs. Survival was estimated using Kaplan-Meier curves, and Cox proportional hazards models were used to explore the impact of the BC subtype and MET status on survival with the time periods as surrogate markers for ATH evolution. RESULTS: During the observation period, 5-year relative survival has improved from 80.3 to 93.6% with an adjusted hazard ratio of 0.54 (P < 0.0001). Successful implementation of ATH has changed the MET pattern. The percentage of liver and CNS METs has more than doubled, the rate of lung METs remains stable, and the rate of bone METs has been reduced by approximately 50%. MFS has been prolonged with a hazard ratio 0.75 (P < 0.0001), but PMS has declined (hazard ratio 1.36; P < 0.0001); however, effects of adjuvant and palliative treatments cannot be separated. These results do not contradict improvements in advanced BC and do not suggest alterations of MET tumour biology by ATH. CONCLUSIONS: Over the past three decades, ATHs have dramatically improved patient survival after BC diagnosis-most likely, by eradicating prevalent micro-METs; as a result, the MET pattern has changed. Eradicating only a portion of the first METs results in delaying the onset of subsequent MET, which leads to an apparently paradoxical effect: an extension of the MET-free interval and a reduction in PMS.

Survival of de novo stage IV breast cancer patients over three decades.

BACKGROUND: De novo stage IV breast cancer patients (BCIV) depict a clinical picture not influenced by adjuvant therapy. Therefore, the time-dependent impact of changes in diagnostics and treatments on progression and survival can best be evaluated in this subgroup. METHODS: BCIV patients from 1978 to 2013 registered in the Munich Cancer Registry were divided into four periods, and the trends were analysed. Survival was estimated by Kaplan-Meier methods, and prognostic factors were fitted with Cox proportional hazard models. RESULTS: Between 1978 and 2013, 88,759 patients were diagnosed with 92,807 cases of invasive and non-invasive BC. Of these patients, 4756 patients had distant metastases (MET) at diagnosis. The 5-year survival rate improved from 17.4 to 24.7%, while the pattern of metastases did not change. Improved staging diagnostics, a screening programme and primary systemic therapy changed the composition of prognostic strata. Patients with a similar composition as the 1978-1987 cohort exhibited a median survival difference of 13 months; however, neither univariate nor multivariate analysis showed a survival effect for the four periods as a surrogate indicator for changing treatments. HER2+ patients have with 27.6 months a slightly longer survival than all other BCIV patients. CONCLUSIONS: Survival of de novo BCIV has only modestly improved since the late 1970s, partially masked by changing distributions of prognostic factors due to changes in diagnostics.

Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. METHODS: The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. RESULTS: Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. CONCLUSIONS: This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. METHODS: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. RESULTS: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. CONCLUSION: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Influence of gender and body hemisphere on the occurrence of wavy ribs: An analysis of spontaneous skeletal abnormalities in Wistar rat fetuses.

The differentiation of background findings from anomalies relevant for the safety evaluation of a future drug is a major task in the interpretation of developmental toxicity studies. The anomaly wavy rib often occurs in litters exposed to the test substance, but is also frequently present in control litters. Therefore, the relevance of this finding for risk assessment is under discussion. We characterized the skeletal morphology of fetuses with wavy ribs from our background data. Differences in the incidence of wavy ribs between the genders, with approximately twice as many male fetuses having wavy ribs, compared to females, and an overrepresentation of the right body hemisphere were observed. Affected fetuses often occurred clustered in single litters. The presented data might be useful for differentiation of spontaneously occurring wavy ribs from abnormal patterns induced by a test substance.

Effect of conductivity changes on the stability of electric signal waveforms in dwarf stonebashers (Mormyridae; Pollimyrus castelnaui, P. marianne).

The dwarf stonebasher sibling species Pollimyrus castelnaui and P. marianne use differences in the electric organ discharges (EODs) for species recognition. As EOD waveforms are affected by water conductivity changes, the reliability of species recognition might be impeded due to natural variability in the environment. EODs of P. castelnaui (N = 8) and P. marianne (N = 8) under high (250 microS/cm) and low (25 microS/cm) conductivity were recorded and compared. Local peaks of the EODs of both species were significantly and predictably modified due to the conductivity change but species-specific differences were always recognizable. The duration of the EODs was not influenced by the conductivity change. Temperature alterations modified the duration in a linear relationship, allowing the determination of Q(10) values (1.6 for P. castelnaui's and 1.7 for P. marianne's EODs). As the species-specific differences are not masked by conductivity effects, EOD discrimination seems to be a reliable species recognition mechanism under natural circumstances.

Mitochondrial markers in the ant Leptothorax rugatulus reveal the population genetic consequences of female philopatry at different hierarchical levels.

Leptothorax rugatulus, an abundant North American ant, displays a conspicuous queen size polymorphism that is related to alternative reproductive tactics. Large queens participate mainly in mating flights and found new colonies independent of their mother colony. In contrast, small queens do not found new colonies independently, but seek readoption into their natal nest which results in multiple-queen colonies (polygyny). Populations differ strongly in the ratio of small to large queens, the prevalent reproductive tactic and colony social structure, according to ecological parameters such as nest site stability and population density. This study compares the genetic structure of two strongly differing populations within the same mountain range. Data from microsatellites and mitochondrial DNA give no evidence for alien reproductives in polygynous colonies. The incidence of alien workers in colonies (as determined by mitochondrial haplotype) was low and did not differ between monogynous and polygynous colonies. We found significant population viscosity (isolation-by-distance) at the mitochondrial level in only the predominantly polygynous population, which supports the theoretical prediction that female philopatry leads to mtDNA-specific population structure. Nuclear and mitochondrial genetic diversity was similar in both populations. The genetic differentiation between the two investigated populations was moderate at the mitochondrial level, but not significantly different from zero when measured with microsatellites, which corroborates limited dispersal of females (but not males) at a larger scale.