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The presence of estrogen receptors in breast cancers is now accepted as a predictor of extended disease-free survival, but the relative value of progesterone receptors for this purpose has not been established. We have examined both receptors along with other risk factors in 189 patients receiving adjuvant therapy for Stage II breast cancer. The presence of either estrogen receptors or progesterone receptors was positively correlated with disease-free survival when analyzed separately, whether or not the adjuvant regimen included an endocrine component. However, when estrogen receptors and progesterone receptors were analyzed together in multivariate models, the presence of progesterone receptors was more significant than that of estrogen receptors for predicting time to recurrence, regardless of what other variables were included in the model. These data suggest that determination of the progesterone-receptor concentration is of equal or greater value than determination of the estrogen-receptor concentration for predicting the disease-free survival of patients with breast cancer. Future trials should include measurement of progesterone receptors.

We report an incidence of thrombosis of 17.6% in 159 patients treated with a five-drug chemotherapy regimen (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) for Stage IV breast carcinoma. Chi-squared analysis of risk factors for thrombosis (ambulatory status, obesity, family history, smoking, diabetes mellitus, hypertension, liver dysfunction, thrombocytosis, and previous endocrine therapy) showed no difference between the patients who had a thromboembolic event and those who did not.Statistical analysis revealed that a significantly higher incidence of thrombosis occurred during the chemotherapy regimen than when off this regimen (P < 0.05). Detailed coagulation studies donie prospectively on 10 patients receiving the five-drug chemotherapy regimen compared with 10 control patients showed a significantly elevated Factor VIII antigen:activity ratio in the group receiving the chemotherapy regimen compared with the control group and normals. These results implicate the chemotherapeutic regimen in the pathogenesis of the increased incidence of thrombosis. The pathophysiology of thrombosis in settings such as this awaits better in vitro tests defining the "hypercoagulable state." Cancer 54:1264-1268, 1984. N INCREASED INCIDENCE OF THROMBOSIS has longA been recognized inThe frequency of such a complication ranges from 5% to 10%4*5 compared to an incidence of 0. I% in the general population.6 The mechanisms inducing altered hemostasis in malignancy are extremely complex,' and the pathophysiology of this "hypercoagulability'" has not been well defined except in a handful of neoplasms.9-' 'We report an incidence of thrombosis of 17.6% in 159 patients treated with a five-drug chemotherapy regimen (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone [CMFW]) for Stage IV metastatic breast carcinoma. Statistical analysis implicated the chemotherapeutic regimen as cause of this increased incidence. Detailed coagulation studies showed changes that could be attributed to the regimen. Awareness of this striking association may lead to future prospective studies that could better define the pathophysiology of chemotherapy-associated hypercoagulability. Materials and MethodsA total of 189 patients with progressive metastatic breast cancer were treated with combination chemotherapy from 197 1 to 1980. Thirty patients were not evaluable because of inadequate clinical data (lost to follow-up, records incomplete). The remaining 159 patients were women with Stage IV breast cancer, none of whom had received previous chemotherapy. Thirty-three patients had received no previous therapy, whereas 128 had previously received endocrine therapy. The dominant sites of disease were bone (82 patients), liver (53), lung (48) and soft tissue (3 1). A modification of the regimen reported by Cooper was used.I3