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. 2021 May 15;27(10):2861-2867.
doi: 10.1158/1078-0432.CCR-20-4635. Epub 2021 Mar 16.

Prognostic Value of ER and PgR Expression and the Impact of Multi-clonal Expression for Recurrence in Ductal Carcinoma in situ: Results from the UK/ANZ DCIS Trial

Mangesh A Thorat  1   2   3 , Pauline M Levey  4 , J Louise Jones  5 , Sarah E Pinder  2   6 , Nigel J Bundred  7   8 , Ian S Fentiman, Jack Cuzick  9
Affiliations

Prognostic Value of ER and PgR Expression and the Impact of Multi-clonal Expression for Recurrence in Ductal Carcinoma in situ: Results from the UK/ANZ DCIS Trial

Mangesh A Thorat et al. Clin Cancer Res. .

Abstract

Purpose: The prognostic value of estrogen receptor (ER)/progesterone receptor (PgR) expression in ductal carcinoma in situ (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS.

Experimental design: Formalin-fixed paraffin embedded tissues were collected from UK/ANZ DCIS trial participants (n = 755), and ER/PgR expression was evaluated by IHC in 181 cases (with recurrence) matched to 362 controls by treatment arm and age. Assays were scored by the Allred method and by a newly devised clonal method-analyses categorizing multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed.

Results: ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared with DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of in situ IBE [OR 4.99; 95% confidence interval (CI), 2.66-9.36; P < 0.0001], but the risk of invasive IBE was not significantly higher (OR 1.72; 95% CI, 0.84-3.53; P = 0.14), P heterogeneity = 0.03. ER was an independent predictor in multivariate analyses (OR 2.66; 95% CI, 1.53-4.61). PgR status did not add to the prognostic information provided by ER.

Conclusions: ER expression is a strong predictor of ipsilateral recurrence risk in DCIS. ER-positive DCIS with distinct ER-negative clones has a recurrence risk similar to ER-negative DCIS. ER should be routinely assessed in DCIS, and ER scoring should take clonality of expression into account.

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Conflict of interest statement

Declaration of interests: The authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1. Kaplan-Meier survival plots* for IBE by ER expression in DCIS, ER multi-clonal cases plotted as a separate category.
* Plots weighted for control sampling in the BSS1 using NestedCohort (20,21) package.
See this image and copyright information in PMC

References

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