<p>The Prognostic Impact of Hormonal Receptor and HER-2 Expression Discordance in Metastatic Breast Cancer Patients</p>

Abstract

These authors contributed equally to this work Background: Hormone receptor (HR) and human epidermal growth factor receptor (HER2) discordance between primary and metastatic breast cancer lesions is common. However, its impact on long-term survival remains unclear. We aimed to determine the prognostic value of this discordance in patients with metastaticf breast cancer (MBC). Methods: A total of 270 patients with MBC who were underwent re-biopsy of progressive metastases at Zhejiang Cancer Hospital from January 1, 2012 to December 31, 2015 with patients consent and then review their primary tumors pathological findings. The HR and HER2 status in both primary and progressive metastatic lesions was determined by immunohistochemistry and/or fluorescence in situ hybridization. The discordance rates were correlated with the clinicopathologic characteristics, metastatic lesions, salvage treatment, and survival analysis in this population. Results: A total of 142 (52.6%) MBC patients were diagnosed with discordant HR and HER2 status. Alterations in estrogen receptor (ER), progesterone receptor (PR), and HER2 status were observed in 20.70%, 37.78%, and 11.48% cases, respectively. Chemotherapy (P=0.0192) and endocrine therapy (P=0.048) significantly affected the conversion of HR status. Endocrine therapy was positively correlated with PR discordance (P=0.002), while ER discordance was associated with adjuvant chemotherapy (P=0.031). Survival analysis showed that ER status alterations between primary and metastatic lesions were associated with overall survival (P=0.002). The clinical prognosis was significantly worse with HR losses than with persistent HR positivity (P=0.023). In Cox multivariate analysis, the loss of HR expression and conversion to triple negative were independent prognostic indicators. Conclusion: Discordance in HR status between primary and metastatic lesions may impact the prognosis of MBC, and HR conversion has independent prognostic value.

Profile and outcome of receptor conversion in breast cancer metastases: a nation‐wide multicenter epidemiological study

“…breast cancer patients. 9,10,[18][19][20][21] However, they conducted the opposite results. Hoefnagel et al 9 found that HR conversion from positive in the primary breast cancer to negative in metastases was associated with poor prognosis in a retrospective study.…”

“…Although receptor status, including ER, PR and HER2, of the primary breast tumors is related to prognosis of breast cancer patients, little information is yet available on whether survival is influenced by receptor conversion in breast cancer metastases. Several studies investigated the association between the receptor conversion and the prognosis of breast cancer patients 9,10,18‐21 . However, they conducted the opposite results.…”

PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects

“…Yang Z et al, conducted a study that included 142 patients with metastatic breast cancer, detecting alterations in estrogen receptor (ER), progesterone receptor (PR), and HER2 status as follows: 20.70%, 37.78%, and 11.48%, respectively [ 159 ].…”

The lingering mysteries of metastatic recurrence in breast cancer

“…Typically, but not always, such alterations are associated with progression on ET therapy. Multiple independent studies have in fact reported significant HR discordance rates between primary breast tumours and matched metastatic lesions [134][135][136][137][138][139][140] (Fig. 4, part II), highlighting several issues.…”