Summary.-In mice with a transplantable mammary carcinoma, treatment with the prostaglandin-synthesis inhibitors flurbiprofen or indomethacin produced various beneficial effects. Survival time after excision of the transplanted tumour was increased, particularly when the drugs were given with the chemotherapeutic agents methrotrexate and melphalan, and there were more disease-free survivors. The combined treatment with flurbiprofen also gave less tumour recurrence at the excision site. Flurbiprofen did not seem to alter the bioavailability of the chemotherapeutic agents.

Summary Prostaglandins may have both undesirable and desirable effects in malignant disease. Their possible roles in breast cancer were studied by examining the relationships between different variables and the amounts of prostaglandin-like material (PG-LM) extracted from 141 breast carcinomas. Univariate analysis indicates a direct correlation with patient age and menopausal status, with a greater yield from cancers of post-compared with pre-menopausal women. Tumours up to 2cm diameter yielded more PG-LM than those measuring >2-5cm. Although there was also a direct correlation with bone metastasis near to the time of surgery, this was because no positive bone scans occurred in patients whose tumours yielded little total PG-LM (<16ng PGE2 equivalents per g tissue). Since tumour PG-LM did not predict later spread to bone, and yields of > 16 ng g -' were similar in the positive and negative bone scan groups, tumour PG-LM appears to be unimportant for skeletal metastasis. There was no obvious relationship of tumour PG-LM to the grade of malignancy, tumour type, amounts of fibrous tissue (and therefore malignant cells), invasion of blood vessels and lymphatics or presence of plasma cells. Multivariate analysis indicates that disease-free survival is longest with an intermediate production of tumour total PG-LM. Of the 82 patients now dead, the cause was attributed to metastatic disease in 69 cases. No relationship of PG-LM to the length of survival was seen with univariate or multivariate analysis. However, when just the post-menopausal patients who died within the first 3 postoperative years were analysed, there was a highly significant inverse correlation between the tumour total PG-LM and the time to death. The reason(s) for these different findings on overall survival compared with just the patients who died are not understood, but the results may indicate that one or more other variables must co-exist with a high tumour PG-LM to hasten death.Many tumours can produce more prostaglandins (PGs) than the normal tissues in which they arise (Bennett, 1979(Bennett, , 1982(Bennett, , 1988. Similarly, more prostglandin-like material (PG-LM), assayed on rat gastric fundus which is most sensitive to PGE2, was extracted from homogenates of human mammary carcinomas than from benign tumours or macroscopically normal breast tissue (Bennet et al., 1977). Various PGs and related substances extracted from breast carcinomas were identified by Stamford et al. (1983) using gas chromatography-mass spectrometry; the products were arachidonate, 12-hydroxy-eicosatetraenoate (12-HETE), thromboxane B2, 15-keto-l 3,14-dihydro-TXB2, 6-keto-PGFJ,, 6,15-diketo-PGF1,,, 615-diketo-1 3,14-dihydro-PGF1,,, PGD2, PGE2 and PGF21,. Quantitative gas chromatography-mass spectrometry showed substantial amounts of 6-keto-PGF, . and some PGD2, PGE2 and PGF20,, with much higher yields of arachidonate (Stamford et al., 1986). It might be expected that these potent substances contribute to breast cancer, but the problem is complex because PGs have numerou...

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Analysis from a multicenter trial of the management of operable breast cancer now in its fifteenth year has confirmed earlier published results that there are no significant differences in survivai and distant recurrence between the two treatment groups ("watch policy" and radiotherapy). However, patients receiving prophylactic radiotherapy at the time of mastectomy continue to have a reduced risk of developing local recurrence as the first sign of treatment failure (p < 0.001). This increased risk is related to various known prognostic indicators such as tumor size and histological grade. Detailed analysis of local recurrence data has shown protection for the radiotherapy patients against recurrence in the chest wall and axiila but not in the supraclavicular area. The question of uncontrolled local disease persisting to death has also been addressed.The Cancer Research Campaign Trial for early breast cancer [I] randomized patients during the 5-year period 1970 to 1975, to one of two forms of treatment: simple mastectomy or simple mastectomy plus radiotherapy. Details of the design of the trial have been extensively discussed in previous articles [1, 2] and will not be mentioned further here. The aim of the trial was to compare mastectomy alone with the more radical treatment of mastectomy plus radiotherapy to the chest wall and all regional lymph nodes. In retrospect, one of the main drawbacks of the protocol was not having some form of axillary node histology available. However, at the time of design, the importance of