TY - JOUR
T1 - Prognostic value of ER and PgR expression and the impact of multi-clonal expression for recurrence in ductal carcinoma in situ
T2 - Results from the UK/ANZ DCIS trial
AU - Thorat, Mangesh A.
AU - Levey, Pauline M.
AU - Louise Jones, J.
AU - Pinder, Sarah E.
AU - Bundred, Nigel J.
AU - Fentiman, Ian S.
AU - Cuzick, Jack
N1 - Funding Information:
M.A. Thorat reports grants from Cancer Research UK and Breast Cancer Research Foundation during the conduct of the study and nonfinancial support from Roche outside the submitted work. S.E. Pinder reports grants from Cancer Research UK and the Australian National Health and Medical Research Council during the conduct of the study. J. Cuzick reports grants from Cancer Research UK and Breast Cancer Research Foundation during the conduct of the study. No disclosures were reported by the other authors.
Funding Information:
This work was supported by Amar Ahmad for help with analyses using Nested-Cohort package (version 1.1-3) in R. This work was funded by Cancer Research UK grants: C569/A12061 (to J. Cuzick, M.A. Thorat) and C569/A16891 (to J. Cuzick, M.A. Thorat).
Publisher Copyright:
© American Association for Cancer Research.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - 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 ¼ 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 ¼ 0.14), Pheterogeneity ¼ 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.
AB - 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 ¼ 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 ¼ 0.14), Pheterogeneity ¼ 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.
UR - http://www.scopus.com/inward/record.url?scp=85106279888&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-4635
DO - 10.1158/1078-0432.CCR-20-4635
M3 - Article
AN - SCOPUS:85106279888
SN - 1078-0432
VL - 27
SP - 2861
EP - 2867
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -
