André‐Pascal Sappino

PURPOSE: No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients. PATIENTS AND METHODS: We reviewed clinical files of 407 breast cancer patients aged >/= 80 years recorded at the Geneva Cancer Registry between 1989 and 1999. Patient and tumor characteristics, general health status, comorbidity, treatment, and cause of death were considered. We evaluated determinants of treatment by logistic regression and effect of treatment on mortality by Cox model, accounting for prognostic factors. RESULTS: Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. CONCLUSION: Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patient's health status, but also should offer the best chance of cure.

To assess the postulated correlation between plasminogen activators (PAs) and malignancy, we determined the mRNA content for urokinase-type (u-PA) and tissue-type (t-PA) enzymes in a prospective series of 29 primary lung and 27 primary breast carcinomas. Dot blots of total RNAs were hybridized with appropriate cRNA probes under conditions that allow quantitative measurement of the mRNA level for each PA. Most tumors (43 of 56) had a u-PA mRNA content higher than the mean + 1 SD of nonmalignant tissue counterparts. A large, 4- to 20-fold, increase in u-PA mRNA content was demonstrated in 14 of 29 lung carcinomas and in 10 of 27 breast carcinomas. A statistically significant correlation (Fisher's test, P = 0.007) was found between elevated u-PA mRNA content in lung carcinomas and the presence of regional lymph node metastases. These results are consistent with a role for u-PA in tumor invasiveness and metastatic propensity and may have important prognostic and therapeutic implications.

Hypertrophic scars and Dupuytren's disease are characterized by the presence of modified fibroblasts or myofibroblasts which are allegedly responsible for tissue retraction and excessive connective tissue production. gamma-Interferon, a cytokine produced by T-helper lymphocytes, has been shown to decrease fibroblast replication, alpha-smooth-muscle actin (the actin isoform characterizing myofibroblasts) expression, and collagen production. We have investigated in an open pilot study the possibility that intralesional injections of gamma-interferon exert a beneficial effect on the evolution of hypertrophic scars and Dupuytren's disease. In the 14 selected patients, gamma-interferon decreased the symptoms and the size of the lesions of both diseases; in hypertrophic scars, immunofluorescence examination showed that alpha-smooth-muscle actin expression also was decreased in myofibroblasts. Moreover, in fibroblasts cultured from 4 patients with hypertrophic scars, gamma-interferon decreased replication and alpha-smooth-muscle actin expression in vitro. Our results suggest that gamma-interferon could represent a useful adjunct to the nonsurgical therapy of hypertrophic scars and Dupuytren's disease. Larger controlled clinical studies, however, should test the validity of these preliminary observations.