Adjuvant chemo-immunotherapy in stage II carcinoma of the breast.

From July of 1974 to June of 1978, 131 patients with Stage II carcinoma of the breast were randomly assigned to one of three treatment arms in order to assess the efficacy of adding immunotherapy to adjuvant chemotherapy. All patients had metastases in the axillary lymph nodes, but no clinical evidence of systemic disease. Prognostic factors were relatively equally distributed among the three treatment arms. All patients received adjuvant chemotherapy consisting of cytoxan, methotrexate, and 5-fluorouracil (CMF). In addition, patients received adjuvant immunotherapy consisting of Bacille Calmette Guerin (BCG) or BCG plus a tumor cell vaccine. This vaccine was a mixture of allogeneic breast cancer cell lines grown in tissue culture. Fourteen patients receiving tumor cell vaccine developed hepatitis B, leading to the abandonment of this arm of the study. Side effects of chemotherapy were tolerable. No statistically significant difference could be demonstrated in recurrence rate or survival. However, the two groups receiving adjuvant chemo-immunotherapy had a slightly shorter time to recurrence and lower overall survival. The use of chemo-immunotherapy as administered in this study did not improve the clinical course of patients with Stage II breast cancer and was associated with significant morbidity.

Psychosocial implications of adjuvant chemotherapy. A two-year follow-up.

Thirty-five women, who had received adjuvant chemotherapy after surgery for Stage II breast carcinoma, were interviewed approximately 21 months after treatment ended. Patients were asked to describe any continuing psychosocial effects of adjuvant chemotherapy in five life areas. All patients had responded to similar interviews 2 1/2 years earlier, while they were receiving chemotherapy. A comparison of first and second interview ratings for disease-free patients indicated that significant improvements in quality of life were reported in four of the five life areas. However, patients did report some continuing disruption in general activity level. Forty-four percent of the patients reported long-term disruption in at least one area, and 56% described continuing physical problems related to chemotherapy. When asked what they would suggest to help other patients adjust to receiving adjuvant chemotherapy, over 50% of the respondents recommended "staying busy" and "getting information." The implications of these findings are discussed.

Systemic therapy for metastatic breast cancer.

The data reviewed in this conference suggest that initial therapeutic decisions for patients with metastic breast cancer be based on the presence or absence of an estrogen receptor in the tumor. Patients with estrogen receptor in their original primary breast cancer or in a subsequent metastitic lesion are candidates for hormonal manipulation, whereas patients lacking estrogen receptor in their tumor are treated for their metastic disease with nonhormonal chemotherapy. Nonhormonal therapy usually consists of a combination of cytotoxic drugs including cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Other programs of combination chemotherapy are under active study, especially programs that include nonspecific immune stimulation with Corynebacterium parvum or bacillus Calmette-Guérin (BCG). Inasmuch as patients with Stage II primary breast cancer frequently have "micrometastatic" disease, combination chemotherapy is also under study as an adjuvant to surgery. Preliminary results strongly support the use of such therapy.

Immunology and adjuvant chemoimmunotherapy of breast cancer.

Antibody against a breast carcinoma antigen was present in patients with breast carcinoma and other cancer more often (P less than .05) than in normal women. The incidence of antibody in women with breast carcinoma correlated with the presence or absence of gross tumor, and the titer of antibody paralleled the clinical course. These results suggest importance of a host-immune response to breast carcinoma. Fifty-seven patients with stage II carcinoma of the breast were entered into a prospective randomized adjuvant chemoimmunotherapy program of cyclophosphamide, methotrexate, and fluorouracil, and BCG vaccine +/- an irradiated allogeneic tumor cell vaccine. After 24 months of study, metastases occurred in two patients (3.5%) and a new primary carcinoma developed in the contralateral breast in two others, for an overall treatment failure rate of 7%. Adjuvant chemoimmunotherapy can delay early recurrence. Long-term follow-up is needed to assess the significance of these results.