OBJECTIVES: Development of diagnostic, therapeutic and preventive measures for breast cancer after cure of Hodgkin disease. STUDY TYPE: Presentation of 4 patients treated conjointly by the Radiotherapy and Gynaecology Surgery Departments of the Rennes University Hospital. RESULTS: Illustrations of difficult management of breast cancer at different stages of diagnosis and therapy. CONCLUSION: A past history of treated Hodgkin disease is a factor of risk for breast cancer and suggests the need for annual mammography screening 10 years after the end of treatment. Though more difficult, mastectomy is recommended over conservative radiosurgical treatment. The choice of drugs for adjuvant chemotherapy should rely on Hodgkin protocols and take into account heart function. Long-term carcinogenic effects of Hodgkin disease treatments requires modulation of the different treatment protocols as a function of stage, clinical and histological factors of prognosis and patient age.

In a serie of 759 patients treated for metastasized cancer of the breast, presence of an hepatic focus was observed in 29 percent of cases. Isolated hepatic metastases were found in 4 percent of cases while in 25 percent they were associated with other tissues. At the time of initial clinical staging, the difference between the hepatic metastases group and the other group stems from the much greater frequency of severity indices in the former group indicating a general and biological transformation of the metastatic tumor(s). At therapeutic staging, the slight effectiveness of medical therapies can be accounted for by the slight tolerance among patients with a secondary hepatic tumor(s). Lastly, it is interesting to note that progesterone receptor presence does not modify the prognosis in hepatic metastases cases.

Two hundred and twenty-three patients with disseminated breast cancer entered in a randomized trial: Group I: 130 patients were given a monthly 5 day- course of a cytotoxic chemotherapy protocol including Adriamycine, Vincristine, Cyclophosphamide, 5 Fluoro-uracile (A.V.L.F.); Group II: 93 patients were given alternatively the same program and a non cross resistant program including: VM 26, Mitomycine C, Methotrexate (V.M.M.). The patients of these groups were randomized into three subgroups: Subgroup O: chemotherapy alone; Subgroup N: chemotherapy + Tamoxifen (20 mg/m2/day); Subgroup NN: chemotherapy + Tamoxifen + Norethisterone (40 mg/m2/day). Objective response rates to cytotoxic chemotherapy were respectively of 65 per cent and 68 per cent in groups I and II of chemotherapy. Further more mean-duration of response and survival were not different. Objective response rates were comparable in the three subgroups of chemo-hormonotherapy. However, the survival was significantly better in the subgroup N (with Tamoxifen) when compared with the subgroup O (without hormonotherapy), and marginally better (p = 0,09) when compared with the NN subgroup (with Tamoxifen + Norethisterone).

Thirteen patients with malignant tumors were entered into a phase I trial with recombinant DNA human alpha 2 interferon (IFN alpha 2). The patients were given I.M. escalating doses of IFN alpha 2 ranging from 1-10(6) to 200-10(6) IU with a 72 hours washout between injections. In the majority of the patients, subjective symptoms were noted: fever, headache, chills, nausea, myalgias. Asthenia, anorexia, drowsiness appeared after the highest doses and disappeared without any sequellae. Leucopenia and thrombopenia were seen in 11 out of 13 patients. Hepatocellular toxicity was observed in 9 cases. Cardiac and vascular functions were not impaired by IFN alpha 2. The pharmacokinetic studies showed a maximum serum concentration between 4 and 6 hours after injection and the peak value was directly proportional to the dose. No neutralizing INF alpha 2 serum factor was detected during the treatment. The peak value for serum beta 2 microglobulin occurred 48 hours after and the N.K. activity was variably modified by IFN alpha 2 injections. A major clinical response was observed in 1 case, a minor response in 3 cases and a stabilisation of the disease in 4 cases.