Discordance Rate in Estrogen Receptor, Progesterone Receptor, HER2 Status, and Ki67 Index Between Primary Unifocal and Multiple Homogenous Breast Carcinomas and Synchronous Axillary Lymph Node Metastases Have an Impact on Therapeutic Decision

Abstract

Background:We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions.Materials and Methods:We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases. We defined as concordant cases in which the primary tumor (PU or PM) and lymph node metastases displayed identical positivity or negativity for ER, PR, HER2, Ki67 and as discordant cases in which there was a mismatch in at least 1 biological parameter among PU and PM tumor and lymph node metastases. Moreover, we defined as concordant cases in which the molecular profile (based on the immunohistochemical evaluation of ER, PR, HER2, and Ki67) was concordant among PU and PM tumors and lymph node metastases and mismatch cases as those in which the molecular profile of the primary tumor differs from one of the lymph node metastases in at least 1 lymph node.Results:The positivity for the biological markers is not stable during the metastatic process. In this study the total rate of discordant cases was 92.7% in PU tumors and 75.7% in PM homogenous tumors (P=0.058, odds ratio=0.245, 95% confidence interval, 0.06-0.991). The total rate of shifted cases was 64.9% in PM tumors and 82.9% in PU tumors. The highest rate of shifting was encountered from Luminal B-like to Luminal A-like. In 11 out of 37 (29.7%) PM and in 17 out of 41 (41.5%) PU cases the subtype shifted to a poorer one with respect to prognosis.Conclusions:The patients in whom the primary tumor is hormone receptor and/or HER2 negative but is positive for these markers in the axillary lymph nodes could become eligible for hormonal treatment and/or trastuzumab treatment, which may significantly improve the patient’s outcome.

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.…”

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.…”

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

“…However, several studies had demonstrated ER, PR and HER2 status instability between primary breast cancer and synchronous axillary lymph node metastasis (Aitken et al, 2010;Rossi et al, 2015). Furthermore, some article recommended to determination of hormone receptors and HER2 status in both primary tumor and synchronous axillary nodal metastasis to guide therapy management and evaluate the recurrent risk also (Lower et al, 2017;Georgescu et al, 2018).…”