Patterns of biomarker expression in patients treated with primary endocrine therapy – a unique insight using core needle biopsy tissue microarray

Parks, R. M.; Albanghali, M. A.; Syed, B. M.; Green, A. R.; Ellis, I. O.; Cheung, K. L.

Abstract

© 2020, The Author(s). Purpose: Prediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET. Methods: Over 37years (1973–2010), 1758 older (≥ 70years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into ‘low’ or ‘high’ based on breast cancer-specific survival (BCSS). Results: From the panel of biomarkers, multivariate analysis showed:High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6months, as opposed to progressive disease.High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression.High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS. Expression of other biomarkers did not show any significant correlation. Conclusions: In addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.

Citation

Parks, R. M., Albanghali, M. A., Syed, B. M., Green, A. R., Ellis, I. O., & Cheung, K. L. (2021). Patterns of biomarker expression in patients treated with primary endocrine therapy – a unique insight using core needle biopsy tissue microarray. Breast Cancer Research and Treatment, 185(3), 647-655. https://doi.org/10.1007/s10549-020-06023-4

• Journal Article Type: Article
• Acceptance Date: Nov 13, 2020
• Online Publication Date: Nov 23, 2020
• Publication Date: 2021-02
• Deposit Date: Nov 16, 2020
• Publicly Available Date: Nov 23, 2020
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 185
• Issue: 3
• Pages: 647-655
• DOI: https://doi.org/10.1007/s10549-020-06023-4
• Keywords: Core needle biopsy, Tissue microarray, Primary breast cancer, Older women,Primary endocrine therapy
• Public URL: https://nottingham-repository.worktribe.com/output/5047581
• Publisher URL: https://link.springer.com/article/10.1007/s10549-020-06023-4
• Additional Information: Received: 14 September 2020; Accepted: 13 November 2020; First Online: 23 November 2020; : ; : The authors declare that they have no conflict of interest.; : All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Nottingham Research and Development committee. The title of the application was ‘Development of a molecular genetic classification of breast cancer;’ project registration number: ‘03HI01’, ethics committee number: C1080301. Informed consent from individual participants was not required as part of this study.