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The addition of hormone therapy to tamoxifen does not prevent hot flashes in women at high risk for developing breast cancer

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Abstract

Tamoxifen significantly reduces the risk of developing breast cancer in women at increased-risk. The usefulness of tamoxifen has been limited by its side effect profile, especially its propensity to worsen vasomotor symptoms. Hormone therapy (HT) has long been utilized to reduce vasomotor symptoms in peri- and post-menopausal women. The aim of this study was to compare the incidence of hot flashes, weight gain and other side effects associated with taking tamoxifen alone versus tamoxifen in combination with HT in high-risk women. One hundred eighty high-risk women were enrolled into one of two parallel study cohorts to receive tamoxifen alone (93 women) or tamoxifen with HT (87 women). Women were monitored at baseline, 3 months and then yearly for assessments of menopausal symptoms and toxicities associated with tamoxifen alone versus tamoxifen plus HT. We also assessed for differences in menopausal symptoms and toxicities by type of HT (estrogen vs. estrogen and progestin combination). Hot flash scores increased at 3 months and at 1 year compared with baseline in women on tamoxifen alone as well as for women on HT. Women on tamoxifen with estrogen only replacement had the greatest increase in hot flash scores, although this was not significantly different than the increase seen with tamoxifen alone. About 47% of participants on tamoxifen gained weight and there was a strong trend towards less weight gain in women on the combination of tamoxifen and HT, most pronounced for those on tamoxifen with estrogen alone replacement therapy. The addition of HT to tamoxifen therapy does not ameliorate tamoxifen-induced vasomotor symptoms. Tamoxifen associated weight gain, however, may be lessened by the addition of HT.

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References

  1. Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467. doi:10.1016/S0140-6736(97)11423-4

    Google Scholar 

  2. Fisher B et al (1996) Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88(21):1529–1542. doi:10.1093/jnci/88.21.1529

    Article  CAS  PubMed  Google Scholar 

  3. Powles TJ et al (2007) Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 99(4):283–290. doi:10.1093/jnci/djk050

    Article  PubMed  CAS  Google Scholar 

  4. Cuzick J et al (2007) Long-term results of tamoxifen prophylaxis for breast cancer-96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 99(4):272–282. doi:10.1093/jnci/djk049

    Article  PubMed  CAS  Google Scholar 

  5. Fisher B et al (2005) Tamoxifen for the prevention of breast cancer: current status of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 97(22):1652–1662

    Article  PubMed  CAS  Google Scholar 

  6. Veronesi U et al (1998) Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian tamoxifen prevention study. Lancet 352(9122):93–97. doi:10.1016/S0140-6736(98)85011-3

    Article  PubMed  CAS  Google Scholar 

  7. Gail MH et al (1989) Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81(24):1879–1886. doi:10.1093/jnci/81.24.1879

    Article  PubMed  CAS  Google Scholar 

  8. Fisher B et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 Study. J Natl Cancer Inst 90(18):1371–1388. doi:10.1093/jnci/90.18.1371

    Article  PubMed  CAS  Google Scholar 

  9. Day R et al (1999) Health-related quality of life and tamoxifen in breast cancer prevention: a report from the national surgical adjuvant breast and bowel project P-1 study. J Clin Oncol 17(9):2659–2669

    PubMed  CAS  Google Scholar 

  10. Powles T et al (1998) Interim analysis of the incidence of breast cancer in the royal Marsden hospital tamoxifen randomised chemoprevention trial. Lancet 352(9122):98–101. doi:10.1016/S0140-6736(98)85012-5

    Article  PubMed  CAS  Google Scholar 

  11. Chang J et al (1996) The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomised, controlled tamoxifen prevention study. Ann Oncol 7(7):671–675

    PubMed  CAS  Google Scholar 

  12. Port ER et al (2001) Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol 8(7):580–585. doi:10.1007/s10434-001-0580-9

    Article  PubMed  CAS  Google Scholar 

  13. NIH (2005) NIH state-of-the-science conference statement on management of menopause-related symptoms. NIH Consens State Sci Statements 22(1):1–38

    Google Scholar 

  14. Maclennan AH et al (2004) Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 18(4):CD002978

    Google Scholar 

  15. Sestak I et al (2006) Influence of hormone replacement therapy on tamoxifen-induced vasomotor symptoms. J Clin Oncol 24(24):3991–3996. doi:10.1200/JCO.2005.04.3745

    Article  PubMed  CAS  Google Scholar 

  16. Kimmick GG et al (2006) Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J 12(2):114–122. doi:10.1111/j.1075-122X.2006.00218.x

    Article  PubMed  Google Scholar 

  17. Loprinzi CL et al (2000) Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 356(9247):2059–2063. doi:10.1016/S0140-6736(00)03403-6

    Article  PubMed  CAS  Google Scholar 

  18. Loprinzi CL et al (2002) Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 20(6):1578–1583. doi:10.1200/JCO.20.6.1578

    Article  PubMed  CAS  Google Scholar 

  19. Borges S et al (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80(1):61–74. doi:10.1016/j.clpt.2006.03.013

    Article  PubMed  CAS  Google Scholar 

  20. Kroenke CH et al (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7):1370–1378. doi:10.1200/JCO.2005.01.079

    Article  PubMed  Google Scholar 

  21. Huang Z et al (1997) Dual effects of weight and weight gain on breast cancer risk. JAMA 278(17):1407–1411. doi:10.1001/jama.278.17.1407

    Article  PubMed  CAS  Google Scholar 

  22. Goodwin PJ et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51. doi:10.1200/JCO.20.1.42

    Article  PubMed  CAS  Google Scholar 

  23. Chlebowski RT, Aiello E, McTiernan A (2002) Weight loss in breast cancer patient management. J Clin Oncol 20(4):1128–1143. doi:10.1200/JCO.20.4.1128

    Article  PubMed  Google Scholar 

  24. Shumaker SA et al (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289(20):2651–2662. doi:10.1001/jama.289.20.2651

    Article  PubMed  CAS  Google Scholar 

  25. Shumaker SA et al (2004) Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291(24):2947–2958. doi:10.1001/jama.291.24.2947

    Article  PubMed  CAS  Google Scholar 

  26. Wassertheil-Smoller S et al (2003) Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 289(20):2673–2684. doi:10.1001/jama.289.20.2673

    Article  PubMed  CAS  Google Scholar 

  27. Anderson GL et al (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291(14):1701–1712. doi:10.1001/jama.291.14.1775

    Article  PubMed  CAS  Google Scholar 

  28. Rossouw JE et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333. doi:10.1001/jama.288.3.321

    Article  PubMed  CAS  Google Scholar 

  29. Sloan JA et al (2001) Methodologic lessons learned from hot flash studies. J Clin Oncol 19(23):4280–4290

    PubMed  CAS  Google Scholar 

  30. Maunsell E et al (2000) A brief pain diary for ambulatory patients with advanced cancer: acceptability and validity. Cancer 88(10):2387–2397. doi:10.1002/(SICI)1097-0142(20000515)88:10<2387::AID-CNCR25>3.0.CO;2-P

    Article  PubMed  CAS  Google Scholar 

  31. Duncan AJ, Sedlacek SM, Holmes FA, Vukelja SJ, Wilkes ST, O’Shaughnessy JA (2002) No difference in menopausal symptoms and severity of hot flashes comparing combined hormone replacement therapy plus tamoxifen to tamoxifen alone in peri- or post-menopausal women at high risk for developing breast cancer. In 25th annual San Antonio breast cancer symposium. Kluwer, San Antonio

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Acknowledgments

This work was funded in part by a research grant to US Oncology from Astra Zeneca.

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Authors and Affiliations

  1. Baylor Sammons Cancer Center, 3535 Worth St, suite 600, Dallas, TX, 75246, USA

    Cynthia R. Osborne, Anita Duncan & Joyce A. O’Shaughnessy

  2. Texas Oncology, P.A., Dallas, TX, USA

    Cynthia R. Osborne, Frankie Holmes, Svetislava Vukelja, Michael Kasper, Sharon Wilks & Joyce A. O’Shaughnessy

  3. US Oncology, Houston, TX, USA

    Cynthia R. Osborne, Scot Sedlacek, Devchand Paul, Frankie Holmes, Svetislava Vukelja, Michael Kasper, Sharon Wilks, Andrew Schneider, Richard McGee, Wally G. Meyer & Joyce A. O’Shaughnessy

  4. Rocky Mountain Cancer Center, Denver, CO, USA

    Scot Sedlacek & Devchand Paul

  5. Cancer Center of South Texas, McAllen, TX, USA

    Sharon Wilks

  6. South Florida Cancer Center, Lake Worth, FL, USA

    Andrew Schneider

  7. Puget Sound Cancer Center, Edmonds, WA, USA

    Richard McGee

  8. Tyler Cancer Center, Tyler, TX, USA

    Svetislava Vukelja

  9. Texas Oncology, Houston, TX, USA

    Frankie Holmes

Authors
  1. Cynthia R. Osborne
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  2. Anita Duncan
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Corresponding author

Correspondence to Cynthia R. Osborne.

Appendix: Hot flash scoring

Appendix: Hot flash scoring

See Tables 5 and 6.

Table 5 Average number of hot flashes in a 24 h period experienced over the past week
Full size table
Table 6 Intensity of hot flashes experienced in the past week
Full size table

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Osborne, C.R., Duncan, A., Sedlacek, S. et al. The addition of hormone therapy to tamoxifen does not prevent hot flashes in women at high risk for developing breast cancer. Breast Cancer Res Treat 116, 521–527 (2009). https://doi.org/10.1007/s10549-008-0284-y

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  • DOI: https://doi.org/10.1007/s10549-008-0284-y

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