Prognostic significance of estrogen, progesterone and HER2 receptors’ status conversion following neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from a tertiary Cancer Center in Saudi Arabia

Background The prognostic impact of neoadjuvant chemotherapy (NAC) on the receptor expression status in patients with locally advanced breast cancer (LABC) is still not fully understood. We aimed to evaluate the changes in hormone (estrogen and progesterone) receptor (HR) and human epidermal growth factor receptor 2 (HER2) status post-NAC and their correlation with survival. Methods Patients with LABC who have received NAC between 2008 and 2015 and have been followed up till December 2019 at the Oncology Center, King Saud University, KSA were analyzed retrospectively. biomarker analysis of ER, PR & HER2 were done using immunohistochemistry (IHC) and Fluorescent in situ hybridization. Results Ninety-one patients fulfilled the inclusion criteria. HR status changed in 21(23.1%) patients, with a significant difference between patients with stable receptors and those with any receptor conversion; p = 0.000. Five (5.5%) initially HER2 negative tumors became HER2 positive and 10 (11%) initially HER2 positive tumors became HER2 negative after NAC. The difference in HER2 expression level before and after NAC was not statistically significant (p = 0.302). Univariate analysis relating patients’ characteristics and 10-years disease-free survival (DFS) showed only significant correlations with the expressions of ER, PR, and any receptor conversion, (ER and/or PR) p< 0.001, p< 0.001, and p = 0.001; respectively. In the univariate analysis, none of the clinicopathological features showed a significant correlation with the OS except for the molecular subtypes P<0.001. Conclusions Patients with LABC have significant changes in the ER and PR receptor status following NAC. Post-NAC expressions change of ER and PR (ER and/or PR) are correlated to DFS. Retesting of the hormone receptors should be considered after NAC in Saudi patients with LABC.

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

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.

Prognostic Value and Influence of Receptor Conversion on Treatment Regimen in Metastatic Breast Cancer at the First Time of Recurrence

<b><i>Purpose:</i></b> At the first time of metastatic breast cancer recurrence, conversion of the receptors status may occur between primary lesions and metastatic lesions, including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Whether the decision of the treatment regimen is based on the primary receptor status or that of metastatic lesions is still unclear. <b><i>Methods:</i></b> This study enrolled 411 female patients with a diagnosis of metastatic breast cancer at the first time of recurrence to explore the influence of receptor conversion on prognosis prediction and treatment regimen of patients with metastatic breast cancer. <b><i>Results:</i></b> ER and PR changes from negative to positive are both prognostic factors for patients with breast cancer. Patients receiving endocrine therapy showed a better survival after recurrence than those using chemotherapy alone in the ER or PR Prim– Met+ subgroup. Patients in the HER2 Prim– Met+ subgroup using HER2-targeted therapy in multilines showed a post-recurrence survival advantage. In the bone re-biopsy subgroup, the PR change from positive to negative appeared to be more frequent than at other re-biopsy sites. <b><i>Conclusions:</i></b> Patients with metastatic breast cancer should perform re-biopsy to clarify the receptor status of the first metastatic lesions, which may provide clinicians valuable evidence to conduct treatments with higher precision.