Predicting breast cancer recurrence

Abstract

The prognostic value of 435 cytochemical, cytometrical, morphological, epidemiological, and clinical variables was analyzed in a prospective study of 179 breast cancer patients followed for five years after mastectomy. A variable reduction was obtained by first selecting variables correlated with recurrence rate in direct (Student's t test) or correlation analysis with consideration of the type of variable analyzed (nominal, interval, ordinal). The 20 variables most strongly correlated with recurrence were analyzed by logistic stepwise regression analysis in order to find out what combination of variables had most discriminatory power in predicting recurrence. It was found that axillary metastization as such was correlated with a combination of variables describing mitotic frequency, size of primary tumor and differentiation of the primary tumor (average cluster size in fine‐needle biopsies). It was also found that there was a strong time dependency in the predictive power of the variables, so that different variable combinations predicted the recurrence rate during the first 2.5 year period (size of axillary metastases and primary tumor, number of lymphocytes around the tumor, mitotic frequency, and degree of differentiation) compared with the second 2.5 year period (variance of DNA content among tumor cell nuclei, number of lymphocytes around the tumor, occurrence of multiple tumors in the operated breast and occurrence of breast cancer among relatives). While other factors previously shown to be correlated with risk of recurrence were also found to be positively correlated here, they were neither as highly predictive as, nor did they increase the predictive value of the above mentioned combined variables. The current study strongly emphasizes that, at the present time, studies of recurrence prediction in human breast cancer should be based on an optimal combination of a number of variables which, independently, influence the prognosis. Further, the current study indicates that prerequisite methods for predicting breast cancer recurrence exist today.

Inhibition of DNA Topoisomerases I and II, and Growth Inhibition of Breast Cancer MCF-7 Cells by Ouabain, Digoxin and Proscillaridin A

“…[4][5][6][7] Patients with breast cancer treated with digitalis have been found to have a lower death rate compared with those not treated with digitalis. [4][5][6][7] Five years after mastectomy the cancer recurrence rate in controls not given digitalis was 9.6-fold that of patients treated with digitalis. [4][5][6][7] Recently, digitalis and other cardiac glycosides in nontoxic concentrations have been shown to induce apoptosis in different malignant cell lines in vitro.…”

“…[1][2][3] Epidemiological studies have shown that digitalis has anti-cancer effects. [4][5][6][7] Patients with breast cancer treated with digitalis have been found to have a lower death rate compared with those not treated with digitalis. [4][5][6][7] Five years after mastectomy the cancer recurrence rate in controls not given digitalis was 9.6-fold that of patients treated with digitalis.…”

In situ hybridisation and S1 mapping show that the presence of infiltrating plasma cells is associated with poor prognosis in breast cancer

“…A review of earlier work (Underwood, 1974) reported that in 8 studies, five showed a correlation between cell infiltration and 'good' prognosis, whereas three were negative. Since that time there have been numerojis additional conflicting rerports of associations between infiltration and for example favourable prognosis (Black et al, 1975;Dawson et al, 1982;Stenkvist et al, 1982), and poor prognosis (Roses et al, 1982;Fisher et al, 1983). However, a consistent theme in more recent studies has been the association of lymphoplasmacytic infiltration and histological features of poor prognosis such as poor grade, nuclear pleomorphism, tumour necrosis and lymph node invasion by tumour (Black et al, 1975;Lauder et al, 1977;Fisher et al, 1983;von Kleist et al, 1987;Zuk & Walker, 1987 Schoorl et al, 1976;Hsu et al, 1981;Hurlimann & Soraga, 1985;Lwin et al, 1985;von Kleist et al, 1987;Zuk & Walker, 1987 (1985) report that B cells can represent up to 48% of the total number of T cells, whilst Zuk and Walker (1987) provide evidence that the proportion of B cells increase relative to T cells in carcinoma as opposed to benign breast, with an overall B:T cell ratio as high as 1:2.…”

Changes in Sodium Pump Expression Dictate the Effects of Ouabain on Cell Growth

“…Of particular significance are studies that indicate the beneficial effects of CTS therapy in women with breast cancer (25)(26)(27)(28)(29). Consistently, recent in vitro and in vivo studies have identified several new CTS compounds that exhibit anti-cancer activities (30 -32).…”