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

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

doi:10.1038/s41416-020-1023-3

Abstract

BackgroundOestrogen 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.MethodsIn 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.ResultsER 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).ConclusionThe 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.

Highlights

Oestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value
High nuclear grade was observed in 60% of cases (388/643), while comedo necrosis was present in approximately two thirds of cases (64%). 300 (47%) patients were treated by breast conserving surgery (BCS), while one third of them received RT (100/300)
This constellation of observed features could be a reflection of the presence of a wellestablished screen programme throughout the period of the study that led to increasing detection of ductal carcinoma in situ (DCIS) of small size and low grade and decease rate of high-risk DCIS 31,32

Summary

Introduction

Oestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value. Conclusion: The strong correlation between DCIS and invasive recurrences ER status and the clinical impact of ET justify discussion of the use of ET in ER-positive DCIS treated by breast conserving surgery. A woman in her 40s or 50s treated with breast conserving surgery (BCS) who subsequently died following DCIS would normally develop an initial local invasive recurrence, subsequently metastatic disease before eventually dying of BC. RT may be omitted for women at low risk of recurrence, clinical and pathological features have not reliably identified patients at low risk of LR following BCS alone, leading to variability in treatment and outcomes of women with DCIS 15. We used a large retrospective cohort of DCIS treated in a single institution to address the outcome of ER-positive DCIS, especially invasive recurrence to consider the utility of routine ER testing in these patients. We have reviewed the randomised studies reporting on adjuvant ET and clinical outcomes of DCIS

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Conclusion