The prognosis of breast cancer patients in relation to the oestrogen receptor status of both primary disease and involved nodes

Abstract

Summary Nodal involvement is accepted as the best single marker of prognosis in breast cancer. However, there is little information on the sub-division of node-positive patients according to the oestrogen receptor status of the nodal tissue. We have previously reported (Eur. J. Ca. 1987, 23, 31) that, in almost all cases, involved nodes are only oestrogen receptor positive (ER+) Collaborative Group, 1988) and, in many countries, nodeinvolved, premenopausal patients are all treated with firstline chemotherapy. Information which argues against such blanket treatment, comes from the multi-centre (GROCTA) study (Boccardo et al., 1990) in Italy. This showed that node positive, oestrogen receptor positive breast cancer patients have both improved disease-free and total survival when treated with hormone-plus-chemotherapy or hormone therapy alone, when compared with chemotherapy alone. These data suggest that hormone therapy has a positive advantage even in the therapy of premenopausal, node-positive patients. To further explore the biological implications of these observations, we now report follow up on a group of 74 breast cancer patients with node-involved disease, on whom full receptor data is available. Patients and methodsA study was set up of 74 consecutive breast cancer patients who, on presentation to the Cancer Hospital in Palermo, were found to have involved axillary nodes, but no other confirmed overt metastases. Both N-l (n = 66) and N-2 (n = 8) patients were included. All patients underwent Pateymodified radical mastectomy. The mean number of nodes from each patient that was pathologically examined was 13 ± 7 (range 4-33 -only seven patients had less than ten nodes examined) and the mean number of histologically involved nodes was 7.8 ± 7. The proportion of nodes investigated that were found to contain malignant cells was similar in all three groups of patients (see later for details) being 54% for those HS + +, 59% for (+ -) and 62% for (--). Of the eight patients with N-2 nodes, four had (--) primaries, three (+ -) and one (+ +).Oestrogen receptor content was determined immediately on the fresh tissue in both a single, involved node (randomly selected by the pathologist from those nodes which were histologically malignant) and in three different parts of each primary (designated central, intermediate and peripheral). In eight cases, three separate nodes were assayed in order to establish the consistency of receptor status. Receptor assay was carried out using our standard seven point Scatchard plot analysis over the range 1-10 x 10-I0 M 3H-oestradiol, with non-specific binding being calculated using competition with 100-fold diethyl stilbestrol at two concentrations of oestradiol (Leake & Habib, 1987).

Biological characteristics of breast cancer at the primary tumour and the involved lymph nodes

“…The authors showed that primary tumours which were uniformly receptor positive mostly (27/29) gave rise to receptor‐positive nodes, whereas heterogeneous primaries most likely (17/20) gave rise to receptor‐negative nodes. In another study by Castagnetta et al (19), among 30 patients with uniformly positive ER across the primary biopsy, 28 had uniformly positive and two had completely negative nodes for ER. Among 24 patients with heterogeneous (+/–) primaries for ER, three had uniformly positive, seven had heterogeneous and 14 had completely negative lymph nodes.…”

Phorbol diester 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) up‐regulates the expression of estrogen receptors in human THP‐1 leukemia cells

“…Accordingly, unstimulated THP-1 cells were found to be ER negative by ICA. The signi®-cance of type I ER stems from the original de®nition of biochemical and functional features relevant to distinct sites of estrogen binding [Clark and Peck, 1979] and, more is illustrated by its discriminant value in the prognosis and treatment of both breast and endometrial cancer patients [Castagnetta et al, 1987a[Castagnetta et al, , 1992. We report that the phorbol diester TPA induces the appearance of type I ER in the soluble fraction of THP-1 cells and increases nuclear type I ER content.…”

Estrogen regulates cytokine production and apoptosis in PMA‐differentiated, macrophage‐like U937 cells

“…This is worth noting since, in our own and other's experience, type I receptors only can be considered functional. In particular, the significance of type I ER stems from the original definition of biochemical and functional features relevant to distinct sites of estrogen binding [Clark and Peck, 1979] and, more, is illustrated by its discriminant value in the prognosis and treatment of both breast and endometrial cancer patients [Castagnetta et al, 1987[Castagnetta et al, , 1992. Therefore, this PMA-induced change in both ER and AR status may suggest that the effects of sex steroids, notably estrogens, on cytokine production in PMA-differentiated U937 cells could be related to the increase of type I nuclear receptor and/or be combined to additional, non-receptorial mechanisms.…”