Clinically Used Breast Cancer Markers Such As Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Are Unstable Throughout Tumor Progression

Abstract

PURPOSE To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. PATIENTS AND METHODS The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. CONCLUSION Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.

Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils

“…There has been a general belief that this is also a natural cause of breast cancer progression in humans. Evidence shows that this is not the case; the majority of ER þ primary breast cancers maintain ER expression in metastases, and nearly a third gain ER expression in metastatic lesions (37). This underscores the importance of understanding estrogendependent mechanisms of breast cancer progression as a prerequisite for finding novel therapeutic targets.…”

Breast Cancer With Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis

“…The prognostic impact of discordance between expression of receptors in the primary and metastatic tumors is not clear. A retrospective study by Lindström et al showed that discordant cases have worse survival [36], whereas a prospective trial by Amir et al failed to demonstrate adverse effects on clinical outcome [37]. In our study, 4 of 18 patients with an HR-positive primary tumor changed to HR-negative status in the BM, whereas 7 of 17 patients with an HR-negative primary tumor changed to HRpositive status in the BM; loss or gain of HR expression in the brain metastases appears to have no significant effect on survival after diagnosis of BCBM.…”

The Relationship Between Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor 2 Expression of Breast Cancer and the Retention Index in Dual Phase 18F-FDG PET/CT

“…It is reported that patients with ER (−) and HER-2 (+) breast cancer have poorer prognoses than patients with ER (+) and HER-2 (−) breast cancer [5,34,35]. Higashi et al [36] reported that RI can predict the hexokinase-II expression and suggested possible prognostic values of RI.…”