Prognostic and Predictive Value of HER2 Expression in Ductal Carcinoma In Situ: Results from the UK/ANZ DCIS Randomized Trial.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
03
04
2021
revised:
23
05
2021
accepted:
30
07
2021
pubmed:
13
8
2021
medline:
16
4
2022
entrez:
12
8
2021
Statut:
ppublish
Résumé
HER2 is overexpressed more frequently in ductal carcinoma in situ (DCIS) than in invasive breast cancer but its prognostic significance and predictive role for radiotherapy has not been clearly established. We investigated the prognostic and predictive value of HER2 overexpression in DCIS. HER2 expression was evaluated by IHC using the HercepTest™ in samples from UK/ANZ DCIS trial participants (n = 755) with IHC 3+ expression categorized as HER2 positive for primary analyses. Sensitivity analyses included HER2 categorization as negative (IHC 0,1+), equivocal (IHC 2+), and positive (IHC 3+) and analyses restricted to a nested case-control component where 181 cases (with recurrence) were matched to 362 controls by treatment arm and age. Two-hundred and forty-five (34.4%) of evaluable 713 samples [181 ipsilateral breast events (IBE)] were HER2 positive. HER2 overexpression was associated with significantly increased risk of IBE [HR = 2.29; 95% confidence interval (95% CI), 1.64-3.14; P < 0.0001] and in situ IBE (DCIS-IBE; HR = 2.90; 95% CI, 1.91-4.40; P < 0.0001), but not of invasive IBE (I-IBE; HR = 1.40; 95% CI, 0.81-2.42; P = 0.23; Pheterogeneity = 0.04). Inclusion of HER2 significantly improved [Δχ2 (1d.f.) 12.25; P = 0.0005] a prognostic model of clinicopathological and treatment variables, HER2 being an independent predictor of IBE (multivariate HR = 1.91; 95% CI, 1.33-2.76; P = 0.0004). Radiotherapy benefit in preventing DCIS-IBE was significantly greater (Pheterogeneity = 0.04) in HER2-positive DCIS (HR = 0.16; 95% CI, 0.07-0.41) compared with HER2-negative DCIS (HR = 0.58; 95% CI, 0.28-1.19). HER2 overexpression is associated with significantly increased risk of in situ recurrence and is also predictive of radiotherapy benefit, with greater reductions in in situ but not invasive recurrences in HER2-positive DCIS.
Identifiants
pubmed: 34380636
pii: 1078-0432.CCR-21-1239
doi: 10.1158/1078-0432.CCR-21-1239
pmc: PMC7612534
mid: EMS132480
doi:
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5317-5324Subventions
Organisme : Cancer Research UK
ID : A12061
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A16891
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C569/A12061
Pays : United Kingdom
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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