We used multiple regression models to assess the influence of disease stage at diagnosis on the 5-year relative survival of 4,478 patients diagnosed with breast cancer in 1990 -1992. The cases were representative samples from 17 population-based cancer registries in 6 European countries (Estonia, France, Italy, Netherlands, Spain and UK) that were combined into 9 regional groups based on similar survival. Five-year relative survival was 79% overall, varying from 98% for early, node-negative (T1N0M0) tumours; 87% for large, node-negative (T2-3N0M0) tumours; 76% for node-positive (T1-3N؉M0) tumours and 55% for locally advanced (T4NxM0) tumours to 18% for metastatic (M1) tumours and 69% for tumours of unspecified stage. There was considerable variation across Europe in relative survival within each disease stage, but this was least marked for early nodenegative tumours. Overall 5-year relative survival was highest in the French group of Bas-Rhin, Cô te d'Or, Hé rault and Isè re (86%), and lowest in Estonia (66%). These geographic groups were characterised by the highest and lowest percentages of women with early stage disease (T1N0M0: 39% and 9%, respectively). The French, Dutch and Italian groups had the highest percentage of operated cases. The number of axillary nodes examined, a factor influencing nodal status, was highest in Italy and Spain. After adjusting for TNM stage and the number of nodes examined, survival differences were greatly reduced, indicating that for these women, diagnosed with breast cancer in Europe during 1990 -1992, the survival differences were mainly due to differences in stage at diagnosis. However, in 3 regional groups, the relative risks of death remained high even after these adjustments, suggesting less than optimal treatment. Screening for breast cancer did not seem to affect the survival patterns once stage had been taken into account.

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To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.

SummaryThe variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.

No abstract