Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers
ABSTRACT Introduction Triple‐Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype, in which targeting the Trophoblast cell‐surface antigen‐2 (Trop‐2), using antibody‐drug conjugates (ADC), results in significant clinical improvement. However, clinicopathological correlations with Tro...
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Wiley
2025-03-01
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| Online Access: | https://doi.org/10.1002/cam4.70615 |
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| author | William Jacot Marie‐Christine Chateau Simon Thezenas Séverine Guiu Nelly Firmin Virginie Lafont Gwendal Lazennec Charles Theillet Florence Boissière‐Michot |
| author_facet | William Jacot Marie‐Christine Chateau Simon Thezenas Séverine Guiu Nelly Firmin Virginie Lafont Gwendal Lazennec Charles Theillet Florence Boissière‐Michot |
| author_sort | William Jacot |
| collection | DOAJ |
| description | ABSTRACT Introduction Triple‐Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype, in which targeting the Trophoblast cell‐surface antigen‐2 (Trop‐2), using antibody‐drug conjugates (ADC), results in significant clinical improvement. However, clinicopathological correlations with Trop‐2 protein expression levels remain limited in TNBC patients. Methods Here we assessed by immunohistochemistry (IHC) using the mouse monoclonal anti‐Trop‐2 antibody (Enzo, Cat. ENZ‐ABS380) cell membrane Trop‐2 expression levels and classified them in 3 H‐Score classes, low (< 100), moderate (100–200), and strong (> 200). We also evaluated potential associations with clinicopathological variables including basal‐like and molecular apocrine phenotypes, immune infiltrate characteristics, PTEN and PIK3CA alterations in a large retrospective series of 228 nonmetastatic TNBC patients. Results Trop‐2 expression was evaluated as low, moderate and strong in 12.3%, 28.9%, and 58.8% of the cases respectively. Only 3 tumors showed no Trop‐2 expression. Interestingly, Trop‐2 expression was not associated with classical breast cancer clinicopathological variables, HER2 levels or molecular subtype, neither did we observe an association with relapse‐free survival. Only a marginal association with pT1 tumors was observed, which tended to express increased levels of Trop‐2 protein. In order to determine possible fluctuations of Trop‐2 protein expression levels during the course of the disease, we studied a second independent cohort of 18 TNBC comprised of serial tissue samples (diagnostic biopsies, surgical resection specimens and corresponding patients‐derived xenografts (PDX)). Trop‐2 levels remained globally stable between cognate tumor samples with only one exception corresponding to a Trop‐2‐negative tumor giving rise to a Trop‐2‐positive PDX. Conclusions As Trop‐2 expression appears nearly constant and independent of classical TNBC variables and outcome, association of anti‐Trop‐2 therapies with other targeted therapies can be evaluated without reducing the population in specific TNBC subgroups. |
| format | Article |
| id | doaj-art-6d497cd0529e4f55a79cafe84f00a8a5 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-6d497cd0529e4f55a79cafe84f00a8a52025-08-20T02:52:48ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70615Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging BiomarkersWilliam Jacot0Marie‐Christine Chateau1Simon Thezenas2Séverine Guiu3Nelly Firmin4Virginie Lafont5Gwendal Lazennec6Charles Theillet7Florence Boissière‐Michot8Department of Medical Oncology Montpellier Cancer Institute Val d'Aurelle Montpellier FranceTranslational Research Unit Montpellier Cancer Institute Val d'Aurelle Montpellier FranceBiometrics Unit, Institut du Cancer Montpellier (ICM) Université de Montpellier Montpellier FranceDepartment of Medical Oncology Montpellier Cancer Institute Val d'Aurelle Montpellier FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) Montpellier FranceMontpellier University Montpellier FranceCNRS UMR9005, Sys2Diag, Alcen Montpellier FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) Montpellier FranceTranslational Research Unit Montpellier Cancer Institute Val d'Aurelle Montpellier FranceABSTRACT Introduction Triple‐Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype, in which targeting the Trophoblast cell‐surface antigen‐2 (Trop‐2), using antibody‐drug conjugates (ADC), results in significant clinical improvement. However, clinicopathological correlations with Trop‐2 protein expression levels remain limited in TNBC patients. Methods Here we assessed by immunohistochemistry (IHC) using the mouse monoclonal anti‐Trop‐2 antibody (Enzo, Cat. ENZ‐ABS380) cell membrane Trop‐2 expression levels and classified them in 3 H‐Score classes, low (< 100), moderate (100–200), and strong (> 200). We also evaluated potential associations with clinicopathological variables including basal‐like and molecular apocrine phenotypes, immune infiltrate characteristics, PTEN and PIK3CA alterations in a large retrospective series of 228 nonmetastatic TNBC patients. Results Trop‐2 expression was evaluated as low, moderate and strong in 12.3%, 28.9%, and 58.8% of the cases respectively. Only 3 tumors showed no Trop‐2 expression. Interestingly, Trop‐2 expression was not associated with classical breast cancer clinicopathological variables, HER2 levels or molecular subtype, neither did we observe an association with relapse‐free survival. Only a marginal association with pT1 tumors was observed, which tended to express increased levels of Trop‐2 protein. In order to determine possible fluctuations of Trop‐2 protein expression levels during the course of the disease, we studied a second independent cohort of 18 TNBC comprised of serial tissue samples (diagnostic biopsies, surgical resection specimens and corresponding patients‐derived xenografts (PDX)). Trop‐2 levels remained globally stable between cognate tumor samples with only one exception corresponding to a Trop‐2‐negative tumor giving rise to a Trop‐2‐positive PDX. Conclusions As Trop‐2 expression appears nearly constant and independent of classical TNBC variables and outcome, association of anti‐Trop‐2 therapies with other targeted therapies can be evaluated without reducing the population in specific TNBC subgroups.https://doi.org/10.1002/cam4.70615basal‐likeexpressionmolecular apocrineprognosistriple‐negative breast cancerTrop‐2 |
| spellingShingle | William Jacot Marie‐Christine Chateau Simon Thezenas Séverine Guiu Nelly Firmin Virginie Lafont Gwendal Lazennec Charles Theillet Florence Boissière‐Michot Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers Cancer Medicine basal‐like expression molecular apocrine prognosis triple‐negative breast cancer Trop‐2 |
| title | Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers |
| title_full | Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers |
| title_fullStr | Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers |
| title_full_unstemmed | Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers |
| title_short | Prognostic Value of Trop‐2 Expression in Nonmetastatic Triple‐Negative Breast Cancer and Correlation With Emerging Biomarkers |
| title_sort | prognostic value of trop 2 expression in nonmetastatic triple negative breast cancer and correlation with emerging biomarkers |
| topic | basal‐like expression molecular apocrine prognosis triple‐negative breast cancer Trop‐2 |
| url | https://doi.org/10.1002/cam4.70615 |
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