Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer (MBC)

Abstract

764 Background: Overexpression of the HER2 receptor protein predicts a worse prognosis and higher metastatic risk in patients (pts) with breast cancer. HER2 positivity also has a strong predictive value for the clinical benefit of trastuzumab (Herceptin, H). The aim of this study was to assess the incidence of HER2 and ER/PR overexpression in patients with newly diagnosed metastatic breast cancer (MBC) and to compare the characteristics and outcomes of pts with HER2-positive and HER2-negative disease. Methods: From June 2000 to November 2001, 96 centres in France participated in a prospective epidemiological study including 741 consecutive pts with newly diagnosed MBC. HER2 and hormonal receptor overexpression was assessed by immunohistochemistry (IHC). Results: Of the 699 evaluable pts aged 25 to 83 (median 54.6) years, 67% were postmenopausal. Tumour characteristics: 29.6% were HER2 3+ by IHC; 61.4% were ER+, and 66.6% either ER+ or PR+. Notably, 22.4% of ER+ and 21.3% of PR+ tumours were also HER2 IHC 3+; furthermore, 23% of ER+ and PR+ tumours showed IHC 3+ staining for HER2. HER2 overexpression was more frequent in invasive ductal carcinoma than in invasive lobular carcinoma (32.1% vs 16.5%; p=0.0033, OR=2.4), and was associated with a shorter time to relapse (p=0.0294). Tumour grade: 92% were SBR grade 2 or 3. 70% had nodal involvement and 32% relapsed within 6 months of MBC diagnosis. However, HER2 overexpression was associated with neither SBR grade nor nodal involvement. Conclusions: These findings confirm that initial HER2 overexpression at presentation is frequent in MBC (close to 30% as assessed by IHC 3+ staining) and is associated with a shorter time to relapse than HER2-negative disease. Importantly, nearly a quarter (22.4%) of ER+ tumours in MBC were also HER2+. This significant group of patients could possibly benefit from the addition of trastuzumab to their treatment. No significant financial relationships to disclose.

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