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Does loss of hormonal receptors influence the pathophysiological characteristics of the HER-2 breast cancer phenotype?

BACKGROUND: Some breast carcinomas (BC) of the HER-2 type respond poorly to endocrine therapy, indicating that hormonal receptor (HR) status possibly impacts the biological criteria of this tumor class. The aim of this study was to compare the clinicopathological characteristics of HR-positive and HR-negative tumors occurring in HER-2 and non-HER-2 BC.

METHODS: Tissue microarray sections from 336 primary invasive BC specimens were stained immunohistochemically with antibodies against HER-2, ER, and PR. Proliferation was assessed using Ki67 and the P53 status was identified.

RESULTS: The HER-2 phenotype was identified in 42/336 (12.5%) specimens, while 293/336 (87.5%) were of the non-HER-2 phenotype. In the non-HER-2 group, 103/293 (35%) were HR-negative tumors. HR negativity was significantly associated with higher tumor grades (P < 0.0001), higher proliferation rates (P < 0.0001), presence of necrosis (P < 0.0001), and with a higher P53 expression (P < 0.0001). There were no differences in patient age, tumor size, LN status, or presence of vascular invasion (VI) between the HR-negative and HR-positive groups. In the HER-2 group, 16/42 (38%) had HR-negative tumors. No significant difference in clinicopathological characteristics, except for tumor grade, was detected between the HR-positive and HR-negative tumors in this group.

CONCLUSION: Loss of HR does not influence the biological features of HER-2 BC. This finding may indicate that some tumors will 'biologically' move from being HER-2-positive/HR-positive tumors to behaving more like HER-2-positive/HR-negative tumors even when ER are present on the cell surface. Further studies are needed to explore this hypothesis and to identify the subset of tumors that will benefit from endocrine therapy.

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