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PubMed1990

Body size and breast cancer prognosis: a critical review of the evidence.

There is currently controversy about the effect of body size on the prognosis of patients with breast cancer. In order to clarify the prognostic importance of body size, and to determine whether the effect varies across subgroups of patients, a critical appraisal of the published literature was undertaken. Thirteen cohort studies and one case-control study were identified that examined the prognostic effect of body size. Methodologic standards were developed that reflected those features of study design considered most important in studies of prognosis in breast cancer, and were independently applied to each report by each of the authors. When the effects of methodologic differences among the studies were controlled, a modest prognostic effect of body size was identified. This effect appeared to be greatest in postmenopausal women, in those with little or no involvement of axillary nodes, and to be independent of other prognostic factors. Additional investigation is recommended to determine the prognostic effects of body size in postmenopausal women with axillary node negative breast cancer and in women receiving systemic adjuvant therapy, and to determine the pathophysiological basis for these effects. Intervention studies to determine the effects of altering body size may also be indicated.

Body Constitution↗

PubMed2006

The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis.

INTRODUCTION: Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help to predict breast cancer prognosis. METHODS: MMP-2, MMP-14 and TIMP-2 expression has been evaluated by 35S mRNA in situ hybridization on paraffin material of 539 breast cancers without distant metastasis at diagnosis and with a median follow-up of 9.2 years. RESULTS: MMP-2 and MMP-14 mRNA was detected primarily in reactive stromal cells whereas TIMP-2 mRNA was expressed by both stromal and cancer cells. Of the three molecules, an adjusted Cox model revealed that high MMP-14 mRNA (> or = 10% cells) alone predicted a significantly shorter overall survival (p = 0.031) when adjusted for clinical factors (tumor size and number of involved lymph nodes). Prognostic significance was lost when further adjusted for Her-2/neu and urokinase-type plasminogen activator (p = 0.284). Furthermore, when all three components were analyzed together, the survival was worst for patients with high MMP-2/high MMP-14/low TIMP-2 (5 year survival = 60%) and best with low MMP-2/low MMP-14/high TIMP-2 (5 year survival = 74%), but the difference did not reach statistical significance (p = 0.3285). CONCLUSION: Of the MMP-14/TIMP-2/MMP-2 complex, MMP-14 was the factor most significantly associated with the outcome of breast cancer and was an independent factor of poor overall survival when adjusted for clinical prognostic factors, but not for certain ancillary markers.

Adult↗

PubMed1991

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2026

Deep learning-based multimodal pathogenomics integration for precision cancer prognosis.

BACKGROUND: Recent studies have revealed valuable prognostic insights in haematoxylin and eosin (H&E)-stained histological sections and transcriptomic profiles, suggesting potential applications in machine learning. However, existing methods lack sufficient intra- and inter-modal interactions, and face challenges in clinical validation due to incomplete multimodal data. METHODS: We proposed PathoGems (PathoGenomics-based integrative survival prediction), a weakly-supervised, interpretable multimodal learning framework that integrates histology and genomic profiles for precise cancer prognosis prediction. To evaluate the robustness of PathoGems, we initially curated a dataset of 1965 cases across four cohorts from The Cancer Genome Atlas (TCGA), including breast, colorectal, glioblastoma, and esophageal cancers. For external validation, PathoGems was further evaluated on four independent cohorts, consisting of 76 breast cancer and 41 esophageal squamous cell carcinoma cases from Zhejiang Cancer Hospital, as well as 102 colorectal cancer and 58 glioblastoma cases from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). RESULTS: PathoGems effectively stratified patients into favorable and unfavorable risk groups, revealing significant differences in histological patterns, genomic features, and overall survival (log-rank test, p < 0.05). Moreover, the model’s predictions are further supported by visualization and transcriptomic analysis, enhancing interpretability and reliability. CONCLUSIONS: By fusing histological and clinicogenomic multimodal models, PathoGems will provide a solid foundation for developing an innovative tool that aids clinicians in making informed decisions and selection personalized treatment strategies for cancer patients.

Humans↗

PubMed2006

Whole genome expression analysis for biologic rational pathway modeling: application in cancer prognosis and therapy prediction.

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer genes including those for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase-type plasminogen activator (PLAU), and plasminogen activator inhibitor-1 (SERPINE1). As such, semi-quantitative expression data provide an almost completely comprehensive background of biological knowledge that can be applied to cancer diagnostics. In clinical terms, expression profiling may be able to provide significant information regarding (i) the identification of high-risk patients requiring aggressive chemotherapy; (ii) the pathway control of therapy predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv) additional support for decisions about switching therapy; (v) target discovery; and (vi) the prediction of the course of new therapies in clinical trials. In conclusion, whole genome expression analysis might be able to determine important genes related to cancer progression and adjuvant chemotherapy resistance, especially in the context of new approaches involving primary systemic chemotherapy. In this review, we will survey the current progress in whole genome expression analyses for cancer prognosis and prediction. Special emphasis is given to the approach of combining biostatistical analysis of expression data with knowledge of biochemical and genetic pathways.

Cluster Analysis↗

PubMed1990

[Interferon-producing capacity in patients with prostate cancer: prognosis value].

The interferon (IFN)-alpha and -gamma producing capacities were measured in 47 patients with prostatic cancer by the whole blood method. The mean IFN-alpha producing capacity in prostatic cancer patients was 3,657 IU/ml, which indicated a significantly (P less than 0.005) lower value than that in healthy male control aged 50 years or more (mean value, 4,988 IU/ml), while the IFN-gamma producing capacity was almost normal. The IFN-alpha and -gamma producing capacities in patients with stage D disease was decreased as compared with that in patients with stage A, B or C. The higher the grade of the diseases, the lower the IFN producing capacity tended to be. In patients with prostatic cancer, the prognosis was worse in low IFN producing capacity group than in normal or high IFN producing capacity group. These results suggest that the measurement of IFN producing capacity is useful for the estimation of the prognosis of patients with prostatic cancer, and that the IFN producing capacity may be a factor which decides the prognosis.

Aged↗

PubMed1992

Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE-3 in breast-cancer prognosis.

Taking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE-3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE-3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin-embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to Kaplan-Meier univariate and Cox proportional-hazards multi-variate analysis. Additionally, traditional prognostic variables for breast-cancer prognosis (grade of differentiation, age, tumor size, axillary-lymph-node involvement and estrogen receptors) were subjected to identical analyses. In uni-variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi-variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary-node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni-variate and multi-variate level. A multi-variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary-node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub-populations of patients with infiltrating breast carcinoma with defined risk functions.

Adolescent↗

PubMed2006

Stage II colon cancer prognosis prediction by tumor gene expression profiling.

PURPOSE: This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated. PATIENTS AND METHODS: Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes. RESULTS: The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy. CONCLUSION: Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

Aged↗

PubMed1996

Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis.

The prognostic significance of p53 gene abnormalities was investigated in 919 primary breast-cancer patients. p53 expression and tumour-cell proliferation fraction determined by MIB-1 count, p53 exon 5 and 6 mutations and HER-2/neu oncogene amplification were detected by immunohistochemistry, PCR-SSCP and slot-blot hybridization, respectively. Increased MIB-1 count, p53 expression, HER-2/neu oncogene amplification and p53 mutations were detected in 33%, 29%, 10% and 8% of tumours, respectively. Statistically significant associations were observed between p53 expression or MIB-1 count and age below 50 years, high-grade tumours, medullary carcinomas, and absence of hormone receptors. p53 mutations were associated with increased MIB-1 count, HER-2/neu oncogene amplification and absence of hormone receptors, but not with age, tumour size or grade, histological subtype, or the number of axillary nodes involved. After a median follow-up of 66 months, p53 expression was observed to be associated with significant increases in risk of both relapse and death from breast cancer, but not after adjusting for the effect of other parameters. In these analyses, MIB-1 count, and not HER-2/neu oncogene amplification, was an independent predictor of prognosis. In node-negative patients, only p53 exon 5 and 6 mutations and MIB-1 count were associated with a statistically significant increase in risk of death from breast cancer, independent of tumour size and ER concentration. We conclude that tumour-cell proliferation fraction, as measured by MIB-1 count, is the most useful parameter of breast-cancer prognosis, with the exception of ER, tumour size and the number of axillary nodes involved.

Adult↗

PubMed1994

Breast cancer prognosis. I. Prognostic factors in patients with node-negative (N0) breast cancer.

Predictors of breast cancer survival were investigated among 196 node-negative (N0) breast cancer patients treated at the Department of Surgery of the University Hospital for Tumors in Zagreb between 1969-1988. Selected prognostic factors included patient age, delay in treatment, tumor size, histologic grade of malignancy, estrogen receptor status, progesterone receptor status, tumor site, and type of surgical treatment. Among these predictors, only tumor size (p < 0.001) and pathohistologic grade of malignancy (p < 0.001) caused significant differences in 5-year overall survival rates (T1-92.1%, T2-89.8%, T3-64.1% and T4-45.4%; grade I-95.0%; II-80.6%; III-63.6%). The authors conclude that among eight selected clinical characteristics, only tumor size and pathohistological malignancy grade can serve as helpful predictors in determination of the probability of 5-year overall survival among node-negative breast cancer patients.

Adult↗

PubMed1989

Concurrent radiation therapy, cis-platinum, and mitomycin C in patients with poor prognosis cancer of the cervix: a pilot study.

Nineteen patients with poor prognosis squamous cell cancer of the cervix were treated with concurrent radiation therapy (RT) and chemotherapy between February 1986 and July 1988. Treatment consisted of intravenous Mitomycin C 10 mg/m2 on days 1 and 43 and cis-platinum 50 mg/m2 on days 1, 22, and 43. All patients received external RT (5,000 cGy in 28 fractions) and brachytherapy (6,000 cGy to point A.) Additionally, patients with paraaortic lymph node involvement received 4,000 cGy paraaortic RT. The toxicity of this regimen was assessed using Southwest Oncology Group criteria. Toxicity was acceptable and did not significantly delay RT. In addition, complete pelvic response was noted in 18 of 19 (95%) patients within month of completion of therapy and maintained despite distant metastases. At the time of this report, 14 of the 19 patients are alive 9-22 months after initiation of treatment. Chemotherapy with cis-platinum and Mitomycin C concurrently with RT is feasible in patients with locally advanced cervical cancer. Further follow-up of our patients is required to determine whether this regimen will have a favorable impact on survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Systematic review of microsatellite instability and colorectal cancer prognosis.

PURPOSE: A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies. METHODS: Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principal outcome measure was the HR. Data from eligible studies were pooled using standard techniques. RESULTS: Thirty-two eligible studies reported survival in a total of 7,642 cases, including 1,277 with MSI. There was no evidence of publication bias. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI, 0.59 to 0.71; heterogeneity P = .16; I(2) = 20%). This benefit was maintained restricting analyses to clinical trial patients (HR = 0.69; 95% CI, 0.56 to 0.85) and patients with locally advanced CRC (HR = 0.67; 95% CI, 0.58 to 0.78). In patients treated with adjuvant fluorouracil (FU) CRCs with MSI had a better prognosis (HR = 0.72; 95% CI, 0.61 to 0.84). However, while data are limited, tumors with MSI derived no benefit from adjuvant FU (HR = 1.24; 95% CI, 0.72 to 2.14). CONCLUSION: CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.

Colorectal Neoplasms↗

PubMed2007

Can biomarkers help us understand the nutritional and lifestyle factors important in cancer prognosis?

In attempting to discover the causes of cancer, investigators have recognized that biomarkers can confirm biological plausibility, enhance relative risks, and serve as surrogate endpoints in observational and intervention studies. In the arena of cancer survival, the potential value of biomarkers is increasingly appreciated. A broad range of histological, cellular, and molecular markers have been identified among persons diagnosed with cancer. Molecular and cellular markers are being used to stage disease, predict prognosis, and target therapeutic interventions. Biomarkers in survivors can also help us to understand factors that influence prognosis by both elucidating pertinent biological pathways and sharpening risk estimates. However, as in the case of incident cancer, the use of biomarkers as surrogate endpoints postdiagnosis is problematic because of the potential existence of alternative pathways to recurrence and death that bypass the surrogate endpoint. In evaluating potential surrogates, an understanding of the causal structure underlying the interrelations of exposures, surrogate, and recurrence or death is essential. Three questions can help to shed light on this structure: 1) What is the relation of the surrogate endpoint to recurrence or death? 2) What is the relation of the intervention (or exposure) to the surrogate? 3) To what extent does the surrogate endpoint mediate the relation between intervention (exposure) and recurrence or death? To address these questions, it is imperative to integrate biomarker studies into ongoing pharmacotherapeutic and lifestyle intervention studies with recurrence or mortality as explicit endpoints.

Biomarkers, Tumor↗

PubMed1983

[Hormone receptors and breast cancer prognosis].

Estradiol and progesterone assays in breast cancer have been developed for ten years and their clinical significance investigated in primary and metastatic tumors. The presence of estradiol and/or progesterone receptor is not related to the extension of the disease, the age of the patient or hormonal status. It seems to be related to the grade of histological differentiation. 1) Clear relationship exists between the presence of estradiol receptor and hormone dependency. 2) Estrogen receptor positive tumors demonstrate a more favorable outcome than the estrogen receptor negative one. According to recent data the presence of progesterone receptor is a better criteria than ER for long term pronostic.

Breast Neoplasms↗

PubMed1995

Influence of prior and subsequent pregnancy on breast cancer prognosis.

PURPOSE AND METHODS: The prognostic influence of pregnancies 5 years before (n = 173) and after (n = 50) breast cancer diagnosis was investigated in 2,119 women less than 50 years of age with a primary operable breast cancer. The main end point was distant metastasis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In the analyses of the effect of pregnancy after diagnosis of breast cancer, a Cox model with a time-dependent covariate was applied. RESULTS: Women with a pregnancy before diagnosis had slightly larger tumors than the control group. However, they did not differ with respect to nodal status and estrogen receptor (ER) status. There was no evidence that women with a pregnancy during the 5-year period preceding breast cancer diagnosis had a worse prognosis compared with women without pregnancy during the same period. Similarly, there was no evidence that women with a pregnancy after breast cancer diagnosis had a worse prognosis. CONCLUSION: The hormonal changes associated with pregnancy thus seem to have little, if any, influence on the prognosis of breast cancer. In the present study, at least, there was no indication of a worse prognosis. In fact, the relative hazard for women who became pregnant after diagnosis of breast cancer in comparison with women without a subsequent pregnancy was 0.48 (P = .14), which suggested a possible decreased risk of distant dissemination.

Adult↗

PubMed1994

Breast cancer prognosis. II. Prognostic factors in patients with node-positive (N1-3) breast cancer.

Predictors of breast cancer survival were investigated among 282 node-positive (N1-3) breast cancer patients treated at the Department of Surgery of the University Hospital for Tumors in Zagreb between 1969-1988. Selected prognostic factors included patient age, delay in treatment, tumor size, type of lymph-node affection, pathohistological grade of malignancy, estrogen receptor status, progesterone receptor status, tumor site, and type of surgical treatment. Among these predictors, only tumor size (p < 0.001), type of lymph-node affection (p < 0.001), malignancy grade (p < 0.001), and progesterone receptor status (p < 0.001) revealed a significant impact on a 5-year overall survival rates (T1-100%, T2-64.5%, T3-54.5% and T4-23.7%; N1-60.2%, N2-20.8%, N3-30.3%; grade I-85.5%, II-59.4%, III-30.5%; PgR+ 63.8%, PgR--26.4%). The authors conclude that among nine selected characteristics, only tumor size, type of lymph-node affection, pathohistological malignancy grade, and progesterone receptor status can be helpful predictors in the determination of the probability of 5-year overall survival among node-positive breast cancer patients.

Adult↗

PubMed1989

Body size and breast cancer prognosis: a statistical explanation of the discrepancies.

A historical cohort of 68 female breast cancer patients from one institution who were enrolled in a multicenter randomized controlled trial between 1971 and 1973 were followed up to the beginning of 1986. Weight and height at the time of mastectomy were transformed into two indices of body size, namely the Quetelet Index and a weight to "ideal weight" ratio. These two indices were analyzed for their relation with overall and disease-free survival, while controlling for the effect of several potential confounding variables. While neither index was linearly related to the hazard of death or recurrence, a significant quadratic (curvilinear) relation was found for both indices and both hazards. In all cases the hazard function was concave up, indicating that not only overweight but also underweight status is predictive of an unfavorable prognosis of breast cancer. This finding offers a possible explanation for the discrepancies among previous studies on this topic.

Adult↗

PubMed2006

[Maxillary sinus cancers: Prognosis and quality of life: a retrospective study of 22 cases].

OBJECTIVES: Maxillary sinus cancer is uncommon. We present a study of 22 cases of patients managed at the Nantes University Hospital for maxillary sinus cancer during the time period 1989-2002. MATERIALS AND METHODS: Clinical and oncological characteristics of the tumors were evaluated. Treatment and results were evaluated in association with the patients' quality of life, estimated with a questionnaire survey sent to surviving patients. RESULTS: Carcinomas predominated (68%). The TNM classification was: T2: 45.5%, T3: 45.5% and T4: 9%. 89% of necks were N0 and 9% were N1. Treatment course (determined after imaging) was surgical removal of the tumor by total maxillectomy: 77.5%; partial maxillectomy: 22.5%, associated with post-operative radiotherapy. Esthetic consequences and disabilities of patients assessed by the questionnaire pointed out that 68% of them were complaining of poor quality of life. Global survival at 12 months was 63%, 20% at 24 months and 9% at 5 years. There were no statistically significant differences between specific survivals according to T-stage nor according to histological features. The difference was significant when surgical removal of the tumour was large according to post-operative histology. CONCLUSION: Authors conclude that maxillary sinus cancers exhibit poor prognosis, and focus on the necessity of quality of life assessment.

Aged↗