Receptor conversion impacts outcomes of different molecular subtypes of primary breast cancer

Abstract

Background: Although the conversion of clinically used breast cancer biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) between primary tumors and metastatic lesions is well recognized, data on whether receptor conversion has an effect on therapy management and survival in patients with metastatic breast cancer is limited. This study aimed to investigate the clinical implications of receptor conversion throughout tumor progression.

Methods: In total, 2450 patients diagnosed with metastatic breast cancer in Tianjin Medical University Cancer Institute and Hospital were analyzed and 426 female patients with available biopsy results from both primary and metastatic sites were included in this study. We investigated the alteration of ER, PR and HER2 during breast cancer progression and evaluated the therapy management and prognostic value of receptor conversion.

Results: The conversion rates of ER, PR, and HER2 between primary tumors and metastasis were 21.1% (McNemar's test p < 0.001), 33.2% (p < 0.001), and 11.6% (p = 0.868), respectively. Evaluation of ER, PR, and HER2 status in multiple consecutive metastases revealed a change in 19.1% (p > 0.05), 23.5% (p = 0.021), and 9.8% (p > 0.05) of patients, respectively. Adjuvant therapy (chemotherapy/endocrine therapy) was related to hormone receptor conversion (p < 0.05). A statistically significant differential survival associated with hormone receptor (ER/PR) conversion (log-rank p < 0.05) was observed. In the multivariate analysis, ER conversion was an independent influence factor of survival (p < 0.05). Molecular typing conversion in primary and metastatic lesions also had a significant effect on survival (p < 0.05). We found that changing treatment based on the receptor conversion could affect clinical outcomes (p < 0.05).

Conclusions: Our findings indicated that receptor conversion during breast tumor progression had a significant effect on survival. Most importantly, our findings proved that patients with receptor conversion benefited from a change in therapy.

Keywords: breast cancer; metastasis; outcomes; primary tumor; receptor conversion; therapy.

Figure 1.

Disease-free survival stratified by hormone receptor status in primary tumor and metastasis. (a) Estrogen receptor status in primary and metastatic sites. (b) Progesterone receptor status in primary and metastatic sites.

Figure 2.

Overall survival analysis for hormone receptor and molecular typing conversion. (a) ER status in primary and metastatic sites. (b) PR status in primary and metastatic sites. (c) Molecular typing in primary and metastatic sites.

Figure 3.

Progression-free survival stratified by hormone receptor conversion and first-line endocrine therapy. (a), (b) First-line endocrine therapy based on hormone receptor conversion. (c), (d) First-line endocrine therapy based on ER conversion.