Breast cancer, prostaglandins and patient survival

Abstract

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...

Fatty Acid Metabolites in Rapidly Proliferating Breast Cancer

“…To clarify the roles of the oxygenases in breast cancer, levels of their metabolites need to be defined and, similar to their parent enzymes, related to factors in the disease that alter survival. Radioimmunoassay studies conducted >20 years ago found that PG-like material in breast cancer was associated with an increase, no change, or a decrease in survival [29] and that PGE-like material was unrelated to tumor grade, estrogen receptors, node metastasis, or survival [30], [31], [32]. Perhaps because of these results and the need for fresh, specially processed tissues for study, newer measurement methods that unambiguously identify the metabolites of the COs and also the LOs in this disease are lacking.…”

Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways

“…The relevance of prostaglandins in breast cancer was studied by Bennett and Rolland more than 20 years ago-they found raised prostaglandin levels in breast cancer tissue and indicated that prostaglandin production may serve as a prognostic marker. [6][7][8] Both COX-2 mRNA and protein levels were found to be raised in human breast cancer, 9 10 which was associated with decreased survival. 11 12 The application of NSAIDs was markedly associated with reduced development and progression of colonic tumours in patients with familial adenomatous polyposis (FAP), 13 14 whereas the data obtained on breast cancer are conflicting.…”

Regulation of interleukin-12 gene expression and its anti-tumor activities by prostaglandin E2 derived from mammary carcinomas

“…Numerous studies have demonstrated that PGs are important regulators of macrophages [16][17][18][19][20]. PGs produced by tumor cells or tumor-associated host cells (macrophages, endothelial cells, and stromal cells) have long been considered to play a stimulating role in the progression and metastasis of a variety of animal and human tumors [21][22][23][24]. The production and release of PGE 2 by tumors, in particular, have been associated with general suppression of immune responses.…”