Biomarker heterogeneity between primary breast cancer and synchronous axillary lymph node metastases

Abstract

Whether the expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) receptor and Ki-67 show concordance between the primary tumors and the synchronous axillary lymph node (ALN) metastases has been discussed in numerous studies. However, to date, the results of these studies remain controversial. Therefore, the present study aimed to investigate whether the expression of ER, PR, HER-2 and Ki-67 was in concordance between the primary tumors and synchronous ALN metastases in patients with operable breast cancer (BC). A total of 60 tissue samples were collected from patients with primary operable BC diagnosed with primary tumors and synchronous ALN metastases. The expression levels of the four biomarkers, ER, PR, HER-2 and Ki-67, were assessed in primary lesions and synchronous ALN metastases samples using immunohistochemistry. The cutoff values were set to 10% for ER and PR, while the labeling index of Ki-67 was set to 14%. The immunostaining intensity of ER and PR was scored as negative (-), 1+, 2+ and 3+. The criteria for HER-2 testing in BC were implemented according to the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines. The concordance rates for ER, PR and HER-2 were 96.7 (58/60), 96.7 (58/60) and 90% (54/60), respectively. In addition, the kappa values of consistency in the primary lesions and the synchronous ALN metastases were 0.773 for ER, 0.654 for PR and 0.785 for HER-2. Furthermore, the P-values of ER, PR and Ki-67 numerical variables between the two groups were 0.393, 0.400 and 0.331, respectively, as demonstrated using a non-parametric Wilcoxon signed rank test. The findings of the present study demonstrated a high degree of concordance between the expression of ER, PR, HER-2 and Ki-67 in the primary tumors and that in the synchronous ALN metastases, suggesting that the BC primary tumor biomarkers may be used for the prognosis of synchronous ALN metastases in patients with operable BC.

Intertumoral Heterogeneity of Primary Breast Tumors and Synchronous Axillary Lymph Node Metastases Reflected in IHC-Assessed Expression of Routine and Nonstandard Biomarkers

“…Several reports indicate that various molecular biomarkers also demonstrate similar expression status in PT and metastatic lesions. For instance, the concordance rates of expression status in both foci have been found to reach 72.2% for ER, 88.9% for PR, and 90.7% for HER2 ( 52 ); rates of 77.6% for ER (κ = 0.534, p < 0.01), 82.2% for PR (κ = 0.640, p < 0.01), 84.1% for HER2 (κ = 0.647, p < 0.01) have also been reported in Chinese women ( 53 ), and rates of 96.7% for ER/PR (κ = 0.773, κ = 0.654, accordingly) and 90% for HER2 (κ = 0.785) have been recently reported ( 54 ).…”

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy

“…Several other studies have already addressed this issue, showing widely variable results spanning from nearly overlapping [29,30] to significantly discordant profiles, sometimes with differences in biomarker status in almost half of the cases [11,14,31]. However, all the aforementioned papers evaluated post-operative specimens, often including patients who had previously received NAC.…”

“…However, all the aforementioned papers evaluated post-operative specimens, often including patients who had previously received NAC. It is well known that systemic therapies can potentially promote changes in biomarker expression [32]; hence, the lack of administration of prior therapies may account, at least in part, for the generally higher PT-ALN agreement rates in studies excluding patients receiving NAC [29]. To the best of our knowledge, differences in critical biomarker expression between PTs and ALN metastases in pre-operative CNBs have not been evaluated yet.…”

The Role of Nodes and Nodal Assessment in Diagnosis, Treatment and Prediction in ER+, Node-Positive Breast Cancer

“…There are a number of biological changes that can occur as the cancer progresses to the nodes, though the rate at which this happens is unclear. Some studies have suggested discordance between the primary and nodal cancer happens often-more than 30% for ER, 40% for PR and 24% for HER2 [108]-and others say it is not often enough to warrant evaluating biomarkers in all positive nodes [109,110], and yet others suggest it is somewhere in between [111,112]. To definitively characterise nodal metastases, it may be necessary to evaluate the same biomarkers in cancerous nodal tissue in addition to the primary tumour, as this information could change the treatment plan for some patients.…”