Breast cancer: Relationship between the size of the primary tumour and the probability of metastatic dissemination

Koscielny, Serge; Tubiana, M; Lê, Monique G.; Valleron, Alain‐Jacques; Mouriesse, H; Contesso, G.; Sarrazin, D.

doi:10.1038/bjc.1984.112

Cited by 332 publications

(203 citation statements)

References 10 publications

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“…Distribution of the threshold volume In a previous paper (Koscielny et al, 1984), independence was assumed between the volume at diagnosis VIT and VOT. Under this assumption, the threshold volume (VOT) distribution was estimated from the relationship between the cumulated proportion (p) of metastases at long term and the logarithm of the tumour volume (VIT) at treatment.…”

Section: Resultsmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 93%

“…For a given tumour, the volume of the primary tumour at which the first metastasis is initiated is noted VOT. This volume is the 'threshold volume' (Koscielny et al, 1984 (Koscielny et al, 1984 …”

Section: Methodsmentioning

confidence: 99%

“…We consider only the patients in whom the clinical size of the primary tumour was assessed: 2,648 patients out of 2,918. We gave in a previous paper (Koscielny et al, 1984) all pertinent infor- …”

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confidence: 99%

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A simulation model of the natural history of human breast cancer

Koscielny¹,

Tubiana²,

Valleron³

1985

Br J Cancer

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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...

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Section: Resultsmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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A simulation model of the natural history of human breast cancer

Koscielny¹,

Tubiana²,

Valleron³

1985

Br J Cancer

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“…The models of Retsky and co-workers are the most similar in spirit to ours, in that they incorporate the dormancy-followed-by-rapid-growth phenomenon revealed by Folkman's work. Although the simulation models in [23]- [27] are more complicated than our model, and in some cases are based on a clever statistical analysis of a wealth of data (e.g., [28]), these studies do not compare different multimodal treatments.…”

Section: Introductionmentioning

confidence: 99%

Analysis and comparison of multimodal cancer treatments

Beil¹,

Wein

2001

Mathematical Medicine and Biology

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We analyze the sequence in which the three most commonly prescribed cancer treatments -surgery (S), chemotherapy (C) and radiotherapy (R) -should be administered. A system of ordinary differential equations is formulated that captures the various local and systemic effects of the three modes of treatment, as well as the first-order effects of the interrelationship between the primary tumor and the distant metastatic tumors, including primary tumor shedding and the primary tumor's effect on the rate of angiogenesis in the metastatic tumors.Under a set of stated assumptions on the parameter values, we find the exact cancer cure probability (subject to toxicity constraints) for the six permutation schedules (i.e., SCR, CSR, CRS, SRC, RSC, RCS) and for two novel schedules, SRCR and RSCR, that apply radiotherapy in disjoint, optimally-timed portions. We show analytically that SRCR and RSCR are the two best-performing (i.e., highest cure probability) schedules among the eight considered. Further, SRCR is shown to be optimal among all possible schedules, provided a modest condition is satisfied on the delay of initial angiogenesis experienced by the patient's dormant tumors.

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Therapeutic Effect of Sentinel Lymphadenectomy in T1 Breast Cancer

1998

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To evaluate whether the tumor status of the sentinel lymph node (SN) would alter the systemic adjuvant therapy administered to patients with T1 breast cancer. Design and Patients: Consecutive breast cancer patients (tumors Յ 2 cm) who underwent successful sentinel lymphadenectomy. Main Outcome Measures: Metastatic tumor in the SN, primary tumor size, recommendations for systemic adjuvant therapy before and after histopathologic evaluation of the SN, and actual systemic adjuvant therapy received by the patient. Results: Of 142 total patients, 14 had T1a tumors; 35, T1b; and 93, T1c. Recommendations for systemic adjuvant therapy were initially determined solely by primary tumor characteristics and menopausal status. These recommendations were compared with recommendations for systemic adjuvant therapy based on tumor characteristics, menopausal status, and SN status; and then were compared with actual systemic adjuvant therapy re

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Breast cancer: Relationship between the size of the primary tumour and the probability of metastatic dissemination

Cited by 332 publications

References 10 publications

A simulation model of the natural history of human breast cancer

A simulation model of the natural history of human breast cancer

Analysis and comparison of multimodal cancer treatments

Therapeutic Effect of Sentinel Lymphadenectomy in T1 Breast Cancer

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