Increased mortality in HER2 positive, oestrogen receptor positive invasive breast cancer: a population-based study

Abstract

Background: This study assessed the impact of human epidermal growth factor receptor 2 (HER2) status on the outcomes in an unselected population of breast cancer patients who did not receive HER2-targeted therapy.

Methods: HER2 status by immunohistochemistry and fluorescence in situ hybridisation was compared with clinicopathological data, overall survival (OS) and disease-free survival (DFS) for all patients presenting with breast cancer over 3 years.

Results: In 865 patients (median follow up 6.02 years), HER2 positivity was identified in 13.3% of all cancers and was associated with higher tumour grade (P<10(-8)), lymphovascular invasion (P<0.001) and axillary nodal metastasis (P=0.003). There was a negative association with oestrogen-receptor (ER) and progesterone-receptor expression (P<10(-8)), but the majority (57%) of HER2+tumours were ER+HER2 positivity was associated with poorer OS (P=0.0046) and DFS (P=0.0001) confined to the lymph node-positive (LN+) and ER+ subgroups.

Conclusion: HER2-positive cancers were less common in this population-based cohort than most selected series. The association of HER2 positivity with poor prognosis was confined to the ER+ and LN+ subgroups. The survival deficit for the 7.5% of patients with ER+/HER2+ cancer compared with ER+/HER2- patients points to a significant subgroup of women who may not (currently) be considered for HER2-directed therapy.

Figure 1

CONSORT diagram of patient and tumour groups. ^a35 patients had 2 tumours, 4 patients had 3 tumours. ^bTwo patients in this group had two tumours, each. HER2, human epidermal growth factor receptor 2; LN, lymph node.

Figure 2

Kaplan–Meier plots of overall survival for HER2 status, (A) lymph node positive, (B) lymph node negative. (C) ER+, (D) ER–. HER2, human epidermal growth factor receptor 2; ER, oestrogen receptor.