Reappraisal of estrogen receptor negativity in Indian breast cancer

Abstract

761 Background: The incidence of estrogen receptor negative (ER negative) invasive breast carcinoma is reported to be as high as 67.6% in India, as compared to 30–33% in the western literature. It is not clear whether the high incidence among Indians is due to genetic differences between the two populations (“true ER negative status”), or an artefact (“false ER negative status”) from the use of suboptimal manual immunohistochemistry techniques. Accurate ER estimation is critical as patients with false ER negative tumors are often denied the benefits of hormonal therapy. Methods: We used automated immunohistochemistry to re-evaluate the ER status in 246 Indian patients with invasive breast carcinomas previously reported as ER negative by manual immunohistochemistry. Tumour blocks used for this study were the same that were used for the manual assay. The automated technique utilized different reagents (all US FDA approved for diagnostic immunohistochemistry) and staining protocols from those used in the manual assays. The “Quick” score method of assessment was used to assess the range of immunostaining. Results: Of the 246 previously ER negative tumors, 99 (40.24%) were found to be ER positive, and 147 (59.76%) tumors remained ER negative (Quick Score 0). Thirty-four of these 99 ER positive tumors (34.3%) had Quick Scores of 6 and 7 (“strong ER expression”) and 55 (55.55%) had Quick Scores between 1 and 5 (“moderate and low ER expression”). Conclusions: Our results indicate that the high incidence of ER negative breast cancer reported from India is most likely due to the use of suboptimal manual assays, rather than true genetic differences. ER expression in breast cancer among Indian women may be much higher than previously believed. Plausible reasons for increased sensitivity in ER detection in the current study include methods of antigen retrieval, differences in reagents, and automation. Optimal antigen retrieval could be the most critical reason for improved detection. Optimal immunohistochemical demonstration of ER is of critical importance. Patients with false ER negative tumours are denied hormonal therapy. Hormonal therapy is more suited in cost and management than chemotherapy in a limited resource country like India No significant financial relationships to disclose.