Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five-drug chemotherapy regimen

Abstract

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

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer

“…This study supports previously published data on the frequency of VTE in breast cancer chemotherapy, with a rate of 17% in advanced breast cancer (Goodnough et al, 1984) and 8% (Weiss et al, 1981;Levine et al, 1988;von Tempelhoff et al, 1996) in early breast cancer patients receiving adjuvant therapy.…”

“…In early breast cancer, VTE occurs in 5 -10% of patients receiving chemotherapy (Weiss et al, 1981;Levine et al, 1988;von Tempelhoff et al, 1996), with a mortality of 0.2 -0.5% (Weiss et al, 1981;Clahsen et al, 1994). Venous thromboembolism rises to approximately 18% in advanced breast cancer (Goodnough et al, 1984), with a mortality of 9%. Approximately two-thirds of all VTEs occur within 3 months of commencing chemotherapy (von Tempelhoff et al, 1996;Seward et al 1999); however, despite this, thromboprophylaxis is rarely used (Kirwan et al, 2003).…”

When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data

“…Previously, in relatively small cohorts of women receiving chemotherapy for breast cancer, risks of VTE have ranged from 5.5% to 8.0% among women with locoregional disease 5,23,24 and from 4.4% to 17.7% in women with metastatic disease. 23,25,26 By using data on 2773 women undergoing chemotherapy for breast cancer, we reported a risk of VTE that was the equivalent of 5% to 6% per year during chemotherapy and in the month after therapy (3.7% of women undergoing chemotherapy developed a VTE either during treatment or in the 3 months after completion of treatment). The risk during therapy was 6.6 times higher than in the same women before therapy when adjusted for other treatment factors.…”

Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients

“…In early breast cancer, VTE occurs in 5 -10% of patients receiving chemotherapy (Weiss et al, 1981;Levine et al, 1988;von Tempelhoff et al, 1996), and it rises up to 18% in advanced breast cancer with 9% mortality (Goodnough et al, 1984;Kirwan et al, 2008).…”