Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: An international tamoxifen exemestane adjuvant multinational trial analysis

Research output: Contribution to journalArticlepeer-review


  • Duveken B.Y. Fontein
  • Caroline Seynaeve
  • Peyman Hadji
  • Elysée T.M. Hille
  • Willemien Van De Water
  • Hein Putter
  • Elma Meershoek Klein Kranenbarg
  • Annette Hasenburg
  • Robert J. Paridaens
  • Jean Michel Vannetzel
  • Christos Markopoulos
  • Yasuo Hozumi
  • John M.S. Bartlett
  • Stephen E. Jones
  • Johan W.R. Nortier
  • Cornelis J.H. Van De Velde

Colleges, School and Institutes

External organisations

  • Leiden University Medical Center - LUMC
  • Erasmus University Medical Center
  • Philipps-Universitat Marburg
  • University Hospital
  • Leuven Cancer Institute
  • Institut du Sein Henri Hartmann
  • Athens University Medical School
  • Jichi Medical University
  • University of Edinburgh, The
  • US Oncology Research


Purpose: Specific adverse events (AEs) associated with endocrine therapy and related to depletion or blocking of circulating estrogens may be related to treatment efficacy. We investigated the relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Patients and Methods: Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were considered. Patients who did not start or who discontinued their allocated therapy and/or had an event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and time-dependent multivariate Cox proportional hazards models assessed survival differences up to 5 years from the start of treatment. Results: A total of 9,325 patients were included. Patients with specific AEs (v nonspecific or no AEs) had better DFS and OS (multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749 [95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation. Conclusion: Certain specific AEs are associated with superior survival outcomes and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy.


Original languageEnglish
Pages (from-to)2257-2264
Number of pages8
JournalJournal of Clinical Oncology
Issue number18
Publication statusPublished - 20 Jun 2013

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