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

Abstract

OBJECTIVES:

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.

• Authors: Christian F Singer, Daphne Gschwantler-Kaulich, Anneliese Fink-Retter, Georg Pfeiler, Ingrid Walter, Gernot Hudelist, Samir Helmy, Anne-Catherine Spiess, Wolfgang Lamm, Ernst Kubista
• Journal: Journal 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
• PMID: 19034514 (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