Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 1107–1118 | Cite as

Clinical and biomarker predictors of side effects from tamoxifen

  • Wendy Lorizio
  • Alan H. B. Wu
  • Mary S. Beattie
  • Hope Rugo
  • Simone Tchu
  • Karla Kerlikowske
  • Elad Ziv


Tamoxifen decreases breast cancer recurrence, mortality, and breast cancer risk in high-risk women. Despite these proven benefits, tamoxifen use is often limited due to side effects. We identified predictors of tamoxifen-induced side effects based on clinical variables and serum tamoxifen metabolite biomarkers in a cross-sectional study of patients taking tamoxifen. We enrolled 241 women and collected data on demographics, tamoxifen use and side effects, as well as potential clinical and serum predictors. We used logistic regression models and adjusted for age, body mass index, ethnicity, education, prior post-menopausal hormone therapy (HT), tamoxifen duration, and endoxifen levels to identify factors associated with side effects. Common tamoxifen attributed side effects were hot flashes (64%), vaginal dryness (35%), sleep problems (36%), weight gain (6%), and depression, irritability or mood swings (6%). In multi-variate models, tamoxifen duration, age, prior post-menopausal HT, and endoxifen levels all predicted side effects. Women who had been on tamoxifen for >12 months were less likely to report side effects (OR 0.15, 95% CI 0.04–0.58) or severe side effects (OR 0.05, 95% CI 0.005–0.58) compared to women on tamoxifen for <12 months. Compared to women younger than 50, women who were age 60–70 and older than 70 were less likely to report side effects (OR 0.22, 95% CI 0.03–1.35; OR 0.13, 95% CI 0.01–0.99; respectively). Women who previously took post-menopausal HT were more likely to report severe side effects. Women with higher endoxifen levels were more likely to report side effects (OR 1.67, 95% CI 1.01–2.77 per standard deviation increase in endoxifen). Clinicians should consider closely monitoring adherence in women taking tamoxifen, especially in younger women, and women who previously took HT. The association between endoxifen levels and side effects is consistent with the data that suggest that endoxifen is the most highly active metabolite of tamoxifen.


Tamoxifen Side effects Predictors Biomarkers Endoxifen Breast cancer treatment 



This work was supported by the National Institute of General Medical Sciences (NIGMS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Award T32 GM007546, University of California San Francisco, Clinical Pharmacology Fellowship Training Program (W. Lorizio); California Breast Cancer Research Program (CBCRP) Grant 14OB-0166 (E. Ziv); National Cancer Institute (NCI) Grant P50 CA58207 funded UCSF Breast SPORE; the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS) National Institutes of Health/National Cancer Institute (NIH/NCI) Grant P01 CA130818-02A1 (M. S. Beattie), and materials and instrumentation for the AmpliChip CYP450 Test were donated by Roche Molecular Systems, Inc. We thank Viktoriya Krepkiy (Ziv Lab) for helping with participants and administrative support.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Wendy Lorizio
    • 1
    • 2
    • 3
    • 10
  • Alan H. B. Wu
    • 4
    • 11
  • Mary S. Beattie
    • 1
    • 3
    • 5
    • 6
    • 12
  • Hope Rugo
    • 3
    • 7
    • 13
  • Simone Tchu
    • 8
    • 11
  • Karla Kerlikowske
    • 9
    • 14
  • Elad Ziv
    • 1
    • 3
    • 5
    • 6
    • 10
  1. 1.Division of General Internal Medicine, Department of MedicineUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Division of Clinical Pharmacology and Experimental Therapeutics, Department of MedicineUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Helen Diller Family Comprehensive Cancer CenterUniversity of California San FranciscoSan FranciscoUSA
  4. 4.Department of Laboratory MedicineUniversity of California San FranciscoSan FranciscoUSA
  5. 5.Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoUSA
  6. 6.Institute for Human GeneticsUniversity of California San FranciscoSan FranciscoUSA
  7. 7.Division of Hematology and Oncology, Department of MedicineUniversity of California San FranciscoSan FranciscoUSA
  8. 8.Department of Biopharmaceutical SciencesUniversity of California San FranciscoSan FranciscoUSA
  9. 9.Division of General Internal MedicineSan Francisco Veterans Affairs Medical CenterSan FranciscoUSA
  10. 10.UCSF Helen Diller Family Cancer Research BuildingSan FranciscoUSA
  11. 11.San Francisco General HospitalSan FranciscoUSA
  12. 12.UCSF Medical Center at Mount ZionSan FranciscoUSA
  13. 13.UCSF Medical Center at Mount ZionSan FranciscoUSA
  14. 14.Department of Medicine and Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoUSA

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