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PubMed2006

Clinical and pathological factors predictive of lymph node status in women with screen-detected breast cancer.

Two thousand one hundred and thirty five asymptomatic invasive breast cancers detected through screening mammography were analysed to identify predictors of lymph node involvement. Multivariable analysis indicated that predictors included larger tumour diameter, an infiltrating ductal or lobular histological type, multifocal disease, a palpable lesion, and a younger age at diagnosis. An association also was found between nodal involvement and the presence of an extensive in situ component (EIC). Grade was associated with nodal involvement as a univariate predictor. It would be more accurate for screening assessment clinics to use models for predicting nodal status that were customised to their own experience rather than generic models developed in other settings that related predominantly to symptomatic cancer. These models could assist clinical decision-making on axillary node dissection and give guidance to pathologists on numbers of tissue sections to examine.

Adenocarcinoma↗
PubMed1998

Prediction of excess risk of long-term cardiac mortality after radiotherapy of stage I breast cancer.

BACKGROUND AND PURPOSE: Excess cardiac mortality has been reported in long-term follow up of breast cancer patients. Due to these findings it has been emphasized that radiotherapy techniques should be designed to minimize cardiac dose. The present study aims to provide risk figures of long-term excess cardiac mortality following radiotherapy for stage I breast cancer patients, using the relative seriality model. The impact of different modifications of the conventional irradiation technique on the calculated risk value is also analyzed. MATERIAL AND METHODS: One hundred consecutive left-sided stage I breast cancer patients were selected. All patients were treated with post-operative radiotherapy, using tangential 6 MV photon beams. The dose planning of each patient was done by means of a three-dimensional dose planning system. The prescribed mean tumor dose was 50 Gy, 2 Gy/fraction, 5 days a week. For each dose plan the differential heart and myocardium dose-volume histogram (DVH) were calculated. The excess risk of late cardiac mortality was predicted for each patient with the relative seriality model, using a parameter set previously determined. Different methods to decrease the risk of excess cardiac mortality (conventional collimation vs. multileaf collimation (MLC), partial blocking of the target in order to spare the heart and finally a general fluence modulation method) were analyzed. RESULTS AND CONCLUSIONS: The mean value of the calculated excess risk was 1.8%, having the heart as organ at risk, and 2.1% having the myocardium as organ at risk. However, a subgroup of patients where the risk increased up to about 9% (heart) and 12% (myocardium) was found. The risk could be substantially decreased either using an extended blocking of the target or applying the general fluence modulation method.

Breast Neoplasms↗
PubMed2006

Dissemination of adjuvant multiagent chemotherapy and tamoxifen for breast cancer in the United States using estrogen receptor information: 1975-1999.

BACKGROUND: Clinical trials have shown tamoxifen to be effective only in women with estrogen receptor (ER)-positive tumors. In a previous model, trends in the utilization of adjuvant therapy were modeled only as a function of age and stage of the disease and not ER status. In this paper, we integrate this previous estimate on the use of adjuvant systemic therapy for breast cancer in the United States with information on ER status from the Patterns of Care (POC) data to estimate the dissemination of adjuvant therapy for women with different ER-status tumors. We also summarize efficacy of adjuvant systemic therapy reported in the overviews of early breast cancer clinical trials. These two inputs, dissemination and efficacy, are key pieces for models that investigate the effect of breast cancer adjuvant therapy on the decline of U.S. breast cancer mortality. METHODS: The adjustments to the previous models are calculated using the POC data on 7116 women with breast cancer diagnosed from 1987 to 1991 and in 1995 who were randomly selected from the Surveillance, and Epidemiology, and End Results (SEER) program registries. The POC data provide more accurate information on treatment and clinical variables (e.g., ER status) than the SEER data because medical records are reabstracted and further verified with treating physicians. RESULTS: Use of multiagent chemotherapy is higher for younger women (<50 years) and for women whose tumors were shown to be ER negative or borderline. The use of tamoxifen is higher among older women and women with ER-positive tumors. After 1980 the combined use of multiagent chemotherapy and tamoxifen for women diagnosed with breast cancer at ages 69 or younger increased more for women whose tumors were ER status positive or unknown than ER status negative. Older women (>69 years) seem to receive almost exclusively tamoxifen irrespective of ER status, except for a small percentage of those with more advanced stages (II- and II+/IIIA) who also receive multiagent chemotherapy. DISCUSSION: The estimated dissemination trends by ER status, based on modeling the POC data, reveal that treatment strategies with demonstrated efficacy in clinical trials have been adopted into practice. The dissemination and efficacy are the two factors necessary to input into models to determine the population impact of these therapies on U.S. breast cancer mortality. The largest decline in mortality would be expected for younger women (<60 years) with ER-positive tumors or whose tumors are of unknown status because of the largest efficacy and dissemination of adjuvant therapy in this group.

Aged↗
PubMed2005

Discovery of highly differentiative gene groups from microarray gene expression data using the gene club approach.

MOTIVATION: It is commonly believed that suitable analysis of microarray gene expression profile data can lead to better understanding of diseases, and better ways to diagnose and treat diseases. To achieve those goals, it is of interest to discover the gene interaction networks, and perhaps even pathways, underlying given diseases from such data. In this paper, we consider methods for efficiently discovering highly differentiative gene groups (HDGG), which may provide insights on gene interaction networks. HDGGs are groups of genes which completely or nearly completely characterize the diseased or normal tissues. Discovering HDGGs is challenging, due to the high dimensionality of the data. RESULTS: Our methods are based on the novel concept of gene clubs. A gene club consists of a set of genes having high potential to be interactive with each other. The methods can (i) efficiently discover signature HDGGs which completely characterize the diseased and the normal tissues respectively, (ii) find strongest or near strongest HDGGs containing any given gene, and (iii) find much stronger HDGGs than previous methods. As part of the experimental evaluation, the methods are applied to colon, prostate, ovarian, and breast cancer, and leukemia and so on. Some of the genes in the extracted signature HDGGs have known biological functions, and some have attracted little attention in biology and medicine. We hope that appropriate study on them can lead to medical breakthroughs. Some HDGGs for colon and prostate cancers are listed here. The website listed below contains HDGGs for the other cancers. AVAILABILITY: HDGG is implemented in C++ and runs on Unix or Windows platform. The code is available at: http://www.cs.wright.edu/~gdong/hdgg/.

Algorithms↗
PubMed1983

Geographic patterns and trends of liver, biliary tract and pancreas cancer mortality in Slovakia.

The age-adjusted mortality rates and trends of primary liver cancer in Slovakia showed during the investigated decade 1968-1977 small reduction in males, accompanied with statistically significant decline in females. The slightly increasing trends of mortality from the cancer of gallbladder and extrahepatic bile ducts were not significant while the growing rates and upward trends of mortality from pancreatic malignant neoplasms were statistically significant for both sexes. Geographic distribution of standardized mortality rates from these cancer sites displayed various differences within the districts of Slovakia during the whole investigated period. The need for further descriptive and analytical studies of these less common cancer sites of the alimentary system using more detailed and classified data on incidence and mortality is stressed.

Biliary Tract Neoplasms↗
PubMed1992

[Prostatic carcinoma: the importance of echographic monitoring of gland volume after radiotherapy].

Prostatic volume modifications were retrospectively analyzed by means of serial endorectal US in 50 patients affected with prostatic adenocarcinoma previously submitted to external radiotherapy. A progressive reduction in glandular volume (of low, medium, and high grade) was observed in 48/50 patients respectively within 3 months, between 3 and 6 months, and 6-9 months after treatment. After 9 months only lesser modifications were observed. A statistically significant correlation (p less than 0.05) was found between volume decrease percentage and histologic grading of the tumor, but not with its stage. Within the groups of patients affected with similar-grade neoplasms, a statistically significant difference (p less than 0.05) was observed, relative to the decrease rate of prostatic volume, between the patients with complete response and those with partial or no response. US monitoring of prostatic volume after radiotherapy, if correlated with histologic grading, can yield early predictive elements as to treatment outcome, thus contributing to select non-responsive patients to submit to biopsy and, if necessary, to therapeutic alternatives or combinations. Longer-term studies are needed to prove its effectiveness, to prognostic purposes, in the single patient.

Adenocarcinoma↗
PubMed2000

p53 protein detection by the western blotting technique in normal and neoplastic specimens of human endometrium.

The aim of the study was to investigate p53 protein expression by the Western blotting technique (estimated by integrated optical density - IOD) in normal (n = 13) and neoplastic (n = 40) human endometrial tissues as well as in a case of uterine carcinosarcoma and in a specimen of the botryoid sarcoma of the uterine cervix. p53 protein levels were correlated with patients' age as well as with conventionally used clinicopathological features of the endometrial neoplasm. A statistically significant difference was noted in p53 levels in the nuclear, but not in the cytoplasmatic, fraction between the normal endometria and endometrial cancer tissues (P < 0.0001). In the neoplastic endometria, nuclear p53 protein expression was higher than in cytoplasmatic fraction, and the difference was significant (P < 0.05). Higher nuclear p53 protein levels correlated with advanced histological grading of endometrioid endometrial carcinomas, but no relationship was noted between p53 protein expression and patients' age, clinical stage, histological type or depth of myometrial invasion. A case of uterine carcinosarcoma and a specimen of a botryoid sarcoma of the uterine cervix expressed nuclear p53 oncoprotein (57 IOD and 89 IOD, respectively). In conclusion, we found a statistically higher nuclear p53 levels in malignant as compared to normal human endometrial specimens by the Western blotting technique. Although there were no significant differences between p53 expression and clinicopathological features of the neoplasm (except poor histological grading), further studies are necessary to evaluate the influence of p53 nuclear/cytoplasmatic levels on the clinical outcome of Polish patients suffering from endometrial cancer.

Age Factors↗
PubMed1995

The Henrietta Banting Breast Centre database: a model for clinical research utilizing a hospital-based inception cohort.

The cohort study design has been used successfully in clinical cancer research. Cohorts, however, are valuable only if they produce results which are valid and generalizable. Some hospital-based inception cohorts satisfy both these requirements and may thus be useful research tools. The development of one such hospital-based cohort, the Henrietta Banting Breast Centre database, is described. This cohort is composed of 1097 women diagnosed with primary breast cancer at Women's College Hospital, Toronto, from January 1977 through December 1986. Details of diagnostic procedures, pathology, treatment, dates and sites of recurrence, and date of death are available on 96% of women. By comparison with published series and with the Ontario Cancer Registry, we have demonstrated validity and generalizability. A major advantage is the ready availability of paraffin tissue blocks on virtually all cases, facilitating analyses of the prognostic importance of specific biologic variables and immunocytochemical hormone assays. Other completed studies and future uses of the cohort are described.

Breast Neoplasms↗
PubMed2003

Linear regression and two-class classification with gene expression data.

MOTIVATION: Using gene expression data to classify (or predict) tumor types has received much research attention recently. Due to some special features of gene expression data, several new methods have been proposed, including the weighted voting scheme of Golub et al., the compound covariate method of Hedenfalk et al. (originally proposed by Tukey), and the shrunken centroids method of Tibshirani et al. These methods look different and are more or less ad hoc. RESULTS: We point out a close connection of the three methods with a linear regression model. Casting the classification problem in the general framework of linear regression naturally leads to new alternatives, such as partial least squares (PLS) methods and penalized PLS (PPLS) methods. Using two real data sets, we show the competitive performance of our new methods when compared with the other three methods.

Algorithms↗
PubMed2002

The use of models in the estimation of disease epidemiology.

OBJECTIVE: To explore the usefulness of incidence-prevalence-mortality (IPM) models in improving estimates of disease epidemiology. METHODS: Two artificial and four empirical data sets (for breast, prostate, colorectal, and stomach cancer) were employed in IPM models. FINDINGS: The internally consistent artificial data sets could be reproduced virtually identically by the models. Our estimates often differed considerably from the empirical data sets, especially for breast and prostate cancer and for older ages. Only for stomach cancer did the estimates approximate to the data, except at older ages. CONCLUSION: There is evidence that the discrepancies between model estimates and observations are caused both by data inaccuracies and past trends in incidence or mortality. Because IPM models cannot distinguish these effects, their use in improving disease estimates becomes complicated. Expert opinion is indispensable in assessing whether the use of these models improves data quality or, inappropriately, removes the effect of trends.

Adolescent↗
PubMed2005

Positron emission tomography elucidates transport system and tumor proliferation in meningiomas.

To test the in vivo transport system and tumor proliferation of meningiomas, in comparison with gliomas, 25 patients with meningiomas and 8 gliomas underwent quantitative kinetic analysis of ([18F])fluoro-2-deoxy-D-glucose (FDG) - positron emission tomography (PET) imaging and immunohistochemical study. Kinetic analysis was obtained by calculation of the rate constants: K1 (ml/g/min), which represents the transport of FDG from plasma to tissue; k2 (min(-1)), which demonstrates the transport back from tissue to plasma; and k3 (min(-1)), an indicator of glucose metabolism, using Gjedde's plot methods in a three-compartment model. Surgical specimens were evaluated by means of three different methods: i) immunoreactivity to vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1), representing the permeability of tumor vessels; ii) immunostaining for von Willebrand Factor (vWF), reflecting vascular surface areas of arterioles; and iii) the MIB-1 labeling index (MIB-1 LI), representing the proliferative potential. K1 was higher in meningiomas than in gliomas and was higher in atypical than in benign meningiomas. k3 was correlated with MIB-1 LI in meningiomas, but not in gliomas. Immunohistochemically, meningiomas were less reactive to VEGF or Glut-1 than gliomas but atypical meningiomas stained more intensely than benign meningiomas. The vascular surface area was significantly larger in meningiomas than in gliomas and atypical meningiomas had high values for both permeability and surface area than benign meningiomas. High values for K1 and k3 indicate the aggressive proliferation of meningiomas and, in atypical meningiomas, the synergistic interaction of the high permeability and the large surface area yielded conditions conducive to glucose metabolism and tumor proliferation. Evaluation of K1 and k3 facilitates to predict the tumor aggressiveness and to optimize the surgical management.

Adult↗