Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low.
Breast Cancer Res
; 25(1): 34, 2023 03 30.
Article
en En
| MEDLINE
| ID: mdl-36998014
ABSTRACT
BACKGROUND:
HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear.METHODS:
We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2low) and 94 HER2-negtive (HER2neg) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2neg vs. HER2low, 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples.RESULTS:
Compared with HER2neg TNBC, HER2low TNBC patients exhibited malignant clinical features with larger tumor size (P = 0.04), more lymph nodes involvement (P = 0.02), higher histological grade of lesions (P < 0.001), higher Ki67 status (P < 0.01), and a worse prognosis (P < 0.001; HR [CI 95%] = 3.44 [2.10-5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2low TNBC but not in HER2neg TNBC patients. ScRNA-seq revealed that HER2low TNBC which showed more metabolically active and aggressive hallmarks, while HER2neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglobulin-related genes (IGHG1, IGHG4, IGKC, IGLC2); this was further confirmed by immunofluorescence in clinical TNBC samples. Furthermore, HER2low and HER2neg TNBC exhibited distinct tumor evolutionary characteristics. Moreover, HER2neg TNBC revealed a potentially more active immune microenvironment than HER2low TNBC, as evidenced by positively active regulation of macrophage polarization, abundant CD8+ effector T cells, enriched diversity of T-cell receptors and higher levels of immunotherapy-targeted markers, which contributed to achieve immunotherapeutic response.CONCLUSIONS:
This study suggests that HER2low TNBC patients harbor more malignant clinical behavior and aggressive tumor biological properties than the HER2neg phenotype. The heterogeneity of HER2 may be a non-negligible factor in the clinical management of TNBC patients. Our data provide new insights into the development of a more refined classification and tailored therapeutic strategies for TNBC patients.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Neoplasias de la Mama Triple Negativas
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Breast Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
China