| Autor: |
Ju, Jie, Du, Feng, Gao, Song-Lin, Si, Yi-Ran, Hu, Nan-Lin, Liu, Dong-Xu, Wang, Xue, Yue, Jian, Zheng, Fang-Chao, Kang, Yi-Kun, Yang, Zi-Xuan, Ma, Fei, Xu, Bing-He, Yuan, Peng |
| Zdroj: |
Breast Cancer Research & Treatment; Jul2022, Vol. 194 Issue 2, p221-230, 10p |
| Abstrakt: |
Background: Hormone receptor-positive and human epidermal growth factor receptor 2-positive (HR+/HER2+ breast cancer comprise approximately 5–10% of all invasive breast cancers. However, the lack of knowledge regarding the complexity of tumor heterogeneity in HR+/HER2+ disease remains a barrier to more accurate therapies. This study aimed to describe the tumor heterogeneity of HR+/HER2+ breast cancer and to establish a novel indicator to identify the HER2-enriched subtype in patients with HR+/HER2+ breast cancer. Methods: First of all, a comprehensive analysis was performed on HR+/HER2+ breast cancer samples from the TCGA (n = 141) and METABRIC (n = 104) databases. We determined the distribution of PAM50 intrinsic subtypes within the two cohorts and compared the somatic mutational profile and RNA expression features between HER2-enriched and non-HER2-enriched subtypes. From this, we constructed a novel marker termed rH/E, which was calculated as ERBB2 expression quantity/(ESR1 expression quantity + 1). Secondly, we performed multiplex immunofluorescence (mIF) to evaluate HER2 and estrogen receptor (ER) expression simultaneously in the third cohort, enrolling 43 cases of early HR+/HER2+ breast cancer from Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). When using mIF, rH/E was adjusted to prH/E, which was calculated as HER2-positive cells%/(ER-positive cells + 1)%. Results: All four main intrinsic subtypes were identified in HR+/HER2+ breast cancer, of which the luminal B subtype was the most common, followed by the HER2-enriched and luminal A subtypes. Significantly increased TP53 and ERBB3 and decreased PIK3CA somatic mutation frequency were observed in the HER2-enriched subtype compared with the non-HER2-enriched subtype. In addition, the HER2-enriched subtype was characterized by significantly higher ERBB2 and lower ESR1 expression. We then constructed a marker termed rH/E to reflect the relative expression of ERBB2 to ESR1 in each patient. rH/E discriminates the HER2-enriched subtype from the better than the expression of ERBB2 or ESR1 alone. In the CAMS cohort, we observed four subtypes of tumor cells: ER+/HER2−, ER+/HER2+, ER−/HER2+, and ER−/HER2−. Tumor cell diversity was common, with 86% of patients having all four subtypes of tumor cells. Moreover, prH/E showed a significant prognostic association in the CAMS cohort. Conclusions: This study furthers our understanding of the complexity of tumor heterogeneity in HR+/HER2+ breast cancer, and suggests that the combined analysis of ERBB2 and ESR1 expression may contribute to identifying patients with specific subtypes in this population. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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