Cell proliferation and its relationship to clinical features and relapse in breast cancers

Gentili, Carla; Sanfilippo, Ornella; Silvestrini, Rosella

doi:10.1002/1097-0142(19810815)48:4<974::aid-cncr2820480420>3.0.co;2-#

Cited by 149 publications

(41 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We supposed that the probability of metastasis is related to the tumour doubling time (as shown by several clinical data) (Tubiana et al, 1981Gentilli et al, 1981;Meyer et al, 1983). In other words, there exists a correlation (R2) between tumour doubling time (DT) and the threshold volume (VOT) (thus, VIT was taken at random, then DT conditionally to VIT, then VOT conditionally to DT).…”

Section: Resultsmentioning

confidence: 99%

A simulation model of the natural history of human breast cancer

Koscielny¹,

Tubiana²,

Valleron³

1985

Br J Cancer

View full text Add to dashboard Cite

Summary In order to assess the time at which the distant metastases were initiated, a model has been developed to simulate the natural history of human breast cancer. The metastasis appearance curves were fitted to those observed for tumours of various sizes among the 2648 patients treated at the Institut Gustave Roussy from 1954 to 1972. The model assumes that metastases are initiated when the tumour reaches a threshold volume (distribution of this volume was estimated in a previous article). Two With exponential growth, it was necessary to introduce correlations to obtain a satisfactory fit of the metastases appearance curves: between the tumour volume at diagnosis and the doubling time (RI = -0.3), and between the tumour volume at metastasis initiation and the doubling time (R2=0.3). The growth duration of the metastases before their detection was found to equal about 18 metastases doubling times at detection and the mean ratio between the doubling time of a tumour and its metastases equal to 2.2.With Gompertzian growth, it was impossible to adjust satisfactorily the proportions of metastases at diagnosis as a function of the primary tumour volume. However, when we ignore this, the best fit was obtained when the duration of metastases growth before detection was about the same as for exponential growth.With either growth pattern, the model predicts that the proportion of patients with metastases would be reduced by -30% if the primary tumours were treated 12 months earlier. This prediction is consistent with the results of the screening programs for breast cancer.In a previous article we studied the relationship between the size of the primary tumour at initial treatment and the incidence of distant metastases during the course of the disease. The data showed that the primary tumour at the time of metastasis initiation is, on the average, only slightly smaller than at the time of tumour diagnosis (Koscielny et al., 1984).This conclusion conflicts with the predictions of previous models of the natural history of breast cancer. Igot & Legal (1968), and later Breuer (1976) assumed that metastases grow exponentially from the time of origin and they extrapolated metastases growth curves backwards in order to determine when the metastases contained one single cell. Assuming identical growth rates for both primary tumours and metastases, they concluded that metastasis commences very early in the development of the primary.This divergence can be explained by the following hypotheses: (a) the number of cells necessary for Correspondence: S. Koscielny. Received 1 January 1985; and in revised form, 11 June 1985. metastasis initiation is much greater than one. (b) the metastasis growth rate is more rapid than the primary tumour one. (c) tumour growth is not exponential.The model proposed in this paper was developed in order to assess the time at which the distant metastases were initiated, taking into account the clinical data, particularly the relationship between primary tumour size and the metastases appearanc...

show abstract

Section: Resultsmentioning

confidence: 99%

A simulation model of the natural history of human breast cancer

Koscielny¹,

Tubiana²,

Valleron³

1985

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…2). Since thymidine-labelling index has been shown to be of prognostic importance in early breast cancer (12,20,271, it would be of interest to do DNA flow cytometry using the blocks taken from tumors which had previously been studied using this technique.…”

Section: Clinical Applicationmentioning

confidence: 99%

Application of DNA flow cytometry to paraffin‐embedded archival material for the study of aneuploidy and its clinical significance

1985

View full text Add to dashboard Cite

By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin‐embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease‐free survival. This influence of DNA content on disease‐free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more turnor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors.

show abstract

“…The measurement of SPF is of considerable clinical interest, as it has been shown in many tumors that prognosis is significantly correlated to the SPF (5, 7,13,15,16,20,29,30).…”

Section: Introductionmentioning

confidence: 99%

Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

et al. 1988

View full text Add to dashboard Cite

The "H-thymidine labeling index (TLI) and the percentage of cells in the S-phase have been determined by autoradiography and by flow cytometry, (FCM), respectively, in six malignant tumors of human origin transplanted on athymic nude mice. The Dean and Jett model and the graphical model were used to determine the percent of S-phase cells by FCM. Cell cycle analysis was performed using 1) no correction for background; 2) an algebraic function for background correction; and 3) an exponential function for background subtraction. Each of these three data sets was evaluated using both the Dean and Jett model and a graphical model for the evaluation of DNA histograms. The S-phase fractions (SPF) were compared to the corresponding labeling index results.SPF without background correction were 1.54 times higher than the TLI. SPF, after correction using the algebraic model, were 1.29-fold higher than the TLI, whereas SPF obtained after background subtraction according to the exponential model were only 1.05-fold higher than the TLI. Student's t-test revealed significant differences between the mean TLI values (16.

show abstract

Cell proliferation and its relationship to clinical features and relapse in breast cancers

Cited by 149 publications

References 17 publications

A simulation model of the natural history of human breast cancer

A simulation model of the natural history of human breast cancer

Application of DNA flow cytometry to paraffin‐embedded archival material for the study of aneuploidy and its clinical significance

Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

Contact Info

Product

Resources

About