Stroke risk and tamoxifen therapy for breast cancer

J Natl Cancer Inst. 2004 Oct 20;96(20):1528-36. doi: 10.1093/jnci/djh285.


Background: Tamoxifen, which is used widely to treat, and increasingly to prevent, breast cancer, has been associated with increased risk of stroke. We assessed the impact of tamoxifen treatment for breast cancer on the risk of stroke, considering dose, duration, and recency of use of tamoxifen and known stroke risk factors.

Methods: We conducted a nested case-control study of stroke after breast cancer among female Los Angeles County residents enrolled in a large health maintenance organization when diagnosed with breast cancer between January 1, 1980, and July 1, 2000. We obtained information on breast cancer treatment and stroke risk factors through medical record review and telephone interviews. The association (odds ratio [OR] and 95% confidence interval [CI]) between tamoxifen and stroke risk was determined by using a conditional logistic regression model, adjusting for menopausal status and history of hypertension and diabetes. All statistical tests were two-sided.

Results: Of 11 045 women with breast cancer, 179 met stroke eligibility criteria and were individually matched to two stroke-free control subjects with breast cancer on age and year of breast cancer diagnosis. The mean age at breast cancer diagnosis was 66.6 years (standard deviation [SD] = 12.3 years), and the mean at-risk period (i.e., the time between breast cancer diagnosis and first stroke or comparable time period for control subjects) was 5.7 years (SD = 4.5 years). Tamoxifen use was not associated with risk of stroke, either overall (OR = 1.0, 95% CI = 0.6 to 1.6) or in subgroups defined by duration, dose, or recency of use. Chemotherapy, but not a specific chemotherapy regimen, was associated with an increased risk of stroke, regardless of tamoxifen use (no tamoxifen use, OR = 2.8, 95% CI = 1.3 to 6.3; tamoxifen use OR = 2.2, 95% CI = 1.2 to 4.1).

Conclusions: Tamoxifen use is not associated with increased stroke risk. Further exploration of possible increased stroke risk following chemotherapy treatment for breast cancer is needed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / prevention & control
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Case-Control Studies
  • Estrogen Antagonists / administration & dosage
  • Estrogen Antagonists / adverse effects
  • Female
  • Humans
  • Logistic Models
  • Los Angeles
  • Middle Aged
  • Odds Ratio
  • Patient Selection
  • Risk Assessment
  • Risk Factors
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Stroke / chemically induced*
  • Tamoxifen / administration & dosage*
  • Tamoxifen / adverse effects*


  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Selective Estrogen Receptor Modulators
  • Tamoxifen