The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review.
BACKGROUND
Tamoxifen therapy for patients with breast carcinoma is perceived as an independent risk factor for venous thromboembolic events (VTE), but the risk associated with other adjuvant therapies is less well recognized.


METHODS
The authors conducted a computerized PubMed literature search for English-language articles published between January 1966 and December 2003. Studies were analyzed with regard to trial design, breast carcinoma staging, adjuvant agent, definition of VTE outcomes, method of VTE case ascertainment, and the presence of concomitant VTE risk factors.


RESULTS
Accurate determination of VTE rates was impaired by the universal lack of routine assessments for asymptomatic VTE. Therefore, only the risk of symptomatic VTE could be derived. The risk of VTE was increased twofold to threefold during tamoxifen or raloxifene use for breast carcinoma chemoprevention. It remains unknown whether the risk is increased further in women with inherited hypercoagulable states. In the setting of early-stage breast carcinoma, the risk of VTE is increased both with tamoxifen use and anastrozole use. Such risk appeared to be lower, albeit not negligible, with anastrozole. Significant methodologic limitations of all available studies in women with advanced-stage breast carcinoma precluded determination of the true VTE risk associated with different adjuvant hormonal agents and made it nearly impossible to compare the risk between different drugs.


CONCLUSIONS
All agents used for breast carcinoma chemoprevention and adjuvant therapy appear to increase the risk of VTE. Available data were insufficient to support any assumptions that newer hormonal forms of hormone manipulation are safer than tamoxifen in women with advanced breast carcinoma.
Section of Hematology and Coagulation Medicine, Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. sdeitcher@nuvelo.com
Steven R
SR
Deitcher
Marcelo P V
MP
Gomes
D000328:Adult; D017677:Age Distribution; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D018570:Risk Assessment; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000453:epidemiology
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen