Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

Abstract

Abstract. In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1. 36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics

“…Between primary and metastatic breast cancer, a meta-analysis of 39 studies showed a total discordance rate of 10.3% for HER2, 19.3% for ER, and 30.9% for PR 9 . Similar findings were confirmed by two other recent reports 38 , 39 , showing HER2 discordance rate of 8.5% and 10%. Most recently, a study with matched primary and metastatic tumors showed 24.6% and 36.9% discordance based on receptor status and PAM50, respectively 10 .…”

Impact of molecular subtypes on metastatic behavior and overall survival in patients with metastatic breast cancer: A single‑center study combined with a large cohort study based on the Surveillance, Epidemiology and End Results database

“…The goal of the present study was to explore the possible impact of molecular subtypes on metastatic behavior and OS in a single-center study combined with a large cohort study from the SEER database. Monitoring the biological behavior of breast cancer may benefit a patient by allowing for the implementation of a personalized treatment strategy ( 22 ).…”

Hormone Receptor Expression in Multicentric/Multifocal versus Unifocal Breast Cancer: Especially the VDR Determines the Outcome Related to Focality

“…We are currently moving toward the era of personalized treatment, which is why knowledge regarding TNM stage and histopathological grading alone, although it supplies independent prognostic information, is inadequate for optimum patient treatment. Consequently, molecular biomarkers, such as ER and PR status, can provide prognostic information and additionally predict the response to therapy, and they have therefore become the center of research [7,33,34,35,36,37,38,39,40,41,42].…”