The relationship between oestrogen receptor (RE) content of primary breast cancer and subsequent prognosis was examined with regard to nodal status. It was found that, within a particular nodal group, patients with tumours containing fully functional RE experienced a longer disease-free interval than those with RE- disease. An earlier observation that RE- primary disease gave rise to distant metastases as first site of recurrence more frequently than did RE+ disease, was not sustained. However, patients with RE+ primary disease had a much reduced chance of dying from cancer within a 3-year period.

This paper is aimed at investigating how metastatic tumour growth influenced the haemostatic system of the host. Blood platelet count, blood fibrinogen level, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) were determined at various intervals during growth and metastasis of a murine fibrosarcoma (mFS6) or one of its sublines with different metastatic capacity. Progressive thrombocytopenia and increase in fibrinogen level were observed during development of the tumour in all the animal groups studied, irrespective of the metastatic potential of the various sublines. No significant changes were observed in the PT or APTT values. These data support the concept that primary rather than metastatic growth influences the haemostatic system of tumour-bearing animals.

Female C3H/HeJ mice bearing intramuscularly transplanted KHT sarcomas were treated with a single dose of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, 30 mg/kg, i.p.) alone or in combination with a single dose of misonidazole (MISO, 1.0 mg/g, i.p.) or its desmethylated metabolite Ro-05-9963 (2.0 mg/g, i.p.). The effectiveness of drug therapy was assessed by a tumour growth-delay assay (i.e. measuring the median time required for tumours to grow to treatment size x 4). The relative efficacy of administering the nitroimidazoles in various schedules ranging from 12 h before to 12 h after BCNU administration also was evaluated. Untreated control KHT tumours grew to the initial size x 4 in a median time of 4 days. No significant growth delay was seen in mice treated with either nitroimidazole alone, whilst treatment with BCNU alone produced a median growth delay of 7 days. Combination chemotherapy with 9963 administration 3 h after BCNU significantly increased the median tumour growth delay to 9 days. However, no significant growth delay was produced in any of the other combinations of these agents. The median growth delay was significantly reduced to 5 days when MISO was administered 3 h before BCNU, whereas MISO administered simultaneously 3,6, or 12 h after BCNU significantly enhanced delays ( 9 days). These results indicate that both MISO and 0063 may be combined with conventional therapeutic agents, in this particular case a nitrosourea, to produce an enhanced tumour response. The production of such a response appears to be nitroimidazole as well as schedule dependent.

Attempts were made to induce immunity to 5 spontaneous rat sarcomas transplanted into syngeneic recipients. Rats were immunized by surgical removal of growing tumour transplants or by treatment with attenuated tumour, followed by challenge with tumour cells in suspension. Two tumours wee apparently not immunogenic, but a low level of immunity was induced against 2, and weak evidence of immunity was observed with another. Induced immunity was individually specific rather than cross-reactive. It is concluded that, contrary to some reports, some spontaneous animal tumours are immunogenic in the strain of origin.

An assay system is described in which effector cells added along with suitable target cells inhibit, in a quantitative fashion, the subsequent uptake of 3H-thymidine by those target cells. Effector cells active in this assay, using embryonic fibroblast cells as targets, develop spontaneously in cultures of mouse lymphoid cells, but are apparently different from those described earlier by investigators of activity in cytotoxic assays. Further evidence is presented to show the development of spleen-derived effector cells with cytostatic activity (for embryonic fibroblast target cells) in mice during the course of normal pregnancy, or growth of spontaneously appearing mammary adenocarcinomas. Indeed, such effector cells can also be found within the growing solid mass itself. Different populations of tumour cells isolated from a solid tumour apparently differ in their susceptibility to growth inhibition by tumour-bearer-derived cytostatic effector cells, a phenomenon which may be related to metastatic spread of tumour cells.

The concentration of cellular oestrogen receptor (RE) was measured in both the soluble and nuclear-pellet fractions of biopsies from 1,000 breast cancers. Data suggest that functional steroid RE is always in equilibrium between the soluble and nuclear fractions. However, biopsies from only one-third of patients contained detectable amounts of high-affinity RE in both fractions. Thirty patients out of 42 (71%) whose biopsies contained RE in both fractions, showed objective remission after receiving some form of hormonal manipulation as sole treatment. Response rates in the other categories ranged from 9% for those whose biopsies contained no detectable RE to 24% for those who displayed soluble RE alone. The presence of RE in both fractions of primary disease, whereas RE-negativity was maintained during progression from primary to secondary disease. Other aspects of RE status in relation to stage of disease are analysed.