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HER2 overexpression and activation, and tamoxifen efficacy in receptor-positive early breast cancer.

AbstractOBJECTIVES:
Tamoxifen is a partial ER antagonist that is highly effective in the treatment of receptor positive breast cancer. It significantly reduces recurrence and improves survival in both pre- and postmenopausal women. Unfortunately, many ER+ positive tumors progress despite tamoxifen treatment and until now, no possibility exists to prospectively identify tamoxifen-resistant tumors. It has been suggested that that in HER2 over-expressing tumors, cross-talk via activated HER2 receptors is a key mechanisms by which tumors become tamoxifen-resistant.
METHODS:
We have therefore used immunohistochemistry to analyze the expression of HER2 and activated ptyr-1248 HER2 in 408 women of ER+, early breast cancer who had received at least 2 years of adjuvant tamoxifen. We then analyzed possible associations between HER2 and pHER2 expression, and prognostic parameters, and evaluated the effect of HER2 expression and survival.
RESULTS:
With HER2 being positive in 12 of 208 (2.9%) of ER+ positive tumors, HER2 overexpression was found to be considerably less common in ER+ tumors than what has been thought previously. The majority of HER2 overexpressing tumors, however, also expressed the activated receptor form (r = 0.664; P < 0.0001). Both HER2 and pHER2 are moderately correlated with Grading (r = 0.138; P = 0.0052 and r = 0.118; P = 0.0241, respectively) and nodal involvement (r = 0.163; P = 0.0018 and r = 0.134; P = 0.016, respectively), but neither HER2 nor its activated form are significant predictors of RFS, DFS, or OS.
CONCLUSIONS:
Taken together, we have demonstrated that in ER+ breast cancer, the HER2 receptor is commonly activated, but its low prevalence in ER+ tumors does not render it a useful prognostic parameter in tamoxifen-treated patients.
AuthorsChristian F Singer, Daphne Gschwantler-Kaulich, Anneliese Fink-Retter, Georg Pfeiler, Ingrid Walter, Gernot Hudelist, Samir Helmy, Anne-Catherine Spiess, Wolfgang Lamm, Ernst Kubista
JournalJournal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 135 Issue 6 Pg. 807-13 (Jun 2009) ISSN: 1432-1335 [Electronic] Germany
PMID19034514 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Receptors, Estrogen
  • Tamoxifen
  • Receptor, ErbB-2
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal (therapeutic use)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Female
  • Humans
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 (biosynthesis)
  • Receptors, Estrogen (biosynthesis)
  • Retrospective Studies
  • Survival Analysis
  • Tamoxifen (therapeutic use)
  • Time Factors
  • Treatment Outcome

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