The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ

Miligy, Islam M; Toss, Michael S; Shiino, Sho; Oni, Georgette; Syed, Binafsha M; Khout, Hazem; Tan, Quing; Green, Andrew R.; Macmillan, R. Douglas; Robertson, John F. R.; Rakha, Emad A

Abstract

Background: Oestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value. In this study, we investigated the value of ER expression in ductal carcinoma in situ (DCIS) in terms of outcome and the impact on ET decision. Methods: In total, 643 pure DCIS, diagnosed at Nottingham University Hospitals, were assessed for ER. Clinicopathological data were correlated against ER status, together with assessment of recurrence rate. Results: ER positivity was observed in 74% (475/643) of cases. ER positivity was associated with clinicopathological variables of good prognosis; however, outcome analysis revealed that ER status was not associated with local recurrence. In the intermediate- and high-grade ER-positive DCIS, 58% (11/19) and 63% (15/24) of the recurrences were invasive, respectively, comprising 7% and 6% of all ER-positive DCIS, respectively. Invasive recurrence in low-grade DCIS was infrequent (2%), and none of these patients died of BC. The ER status of the recurrent invasive tumours matched the primary DCIS ER status (94% in ipsilateral and 90% of contralateral recurrence). Conclusion: The strong correlation between DCIS and invasive recurrence ER status and the clinical impact of ET justify discussion of the use of ET in ER-positive DCIS treated by breast-conserving surgery. The excellent outcome of low-grade DCIS, which was almost always ER-positive, does not, in the opinion of authors, justify the use of risk-reducing ET. Therefore, the decision on ET for DCIS should be personalised and consider grade, ER status and other characteristics.

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2020
• Online Publication Date: Aug 10, 2020
• Publication Date: Nov 10, 2020
• Deposit Date: Jul 8, 2020
• Publicly Available Date: Feb 11, 2021
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Peer Reviewed: Peer Reviewed
• Volume: 123
• Issue: 10
• Pages: 1513-1520
• DOI: https://doi.org/10.1038/s41416-020-1023-3
• Keywords: DCIS; Oestrogen Receptors; nuclear grade; tumour recurrence; endocrine therapy Running title: Significance of ER expression in DCIS 2
• Public URL: https://nottingham-repository.worktribe.com/output/4757099
• Publisher URL: https://www.nature.com/articles/s41416-020-1023-3
• Additional Information: Received: 26 March 2020; Revised: 7 July 2020; Accepted: 22 July 2020; First Online: 10 August 2020; : This work obtained ethics approval by the North West-Greater Manchester Central Research Ethics Committee under the title: Nottingham Health Science Biobank (NHSB), reference number 15/NW/0685. All patients included were consented to participate in the study and to use their materials in research. All samples from Nottingham used in this study were pseudo-anonymised and stored in compliance with the UK Human Tissue Act. The study was performed in accordance with the Declaration of Helsinki.; : Not applicable.; : The authors confirm that data that have been used are available on reasonable request.; : The authors declare no competing interests.; : Not applicable.