Receptor Status Accuracy in Breast Cancer: Core Biopsy or Excision? A Mini Review

With the advent of minimally invasive surgical techniques core needle biopsy (CNB) has emerged as an accurate method of obtaining representative...


Introduction
With the increased prevalence of breast cancer internationally, efficient, cost effective and reliable diagnostic methods are continuously sought. In the emerging era of minimally invasive procedures, coupled by the concordance of both excisional biopsies (EB) with core needle biopsies (CNB), the surgical practice has witnessed a decline in diagnostic surgical excisions [1]. Because of the increased incidence of detected Ductal Carcinoma in Situ (DCIS), fine needle aspiration cytology has become less reliable in obtaining adequate diagnostic samples. On the other hand, the currently widely used CNB in breast lesions has gained popularity over recent years due to the high accuracy in tissue diagnosis obtained from adequate diagnostic samples. Clinicians base their management strategy on the histological diagnosis and hormonal receptors (HR) status in [2]. Chemotherapy treatment, in particular relies on CNB and accurate reporting of HR results [3]. Several studies have demonstrated high concordance rate between CNB and EB in terms of HR status. [2][3][4][5][6] Yet, re-biopsy is strongly indicated in metastatic breast cancer, which may show high discordance between primary and metastatic disease [7].

Materials and Methods
All patients diagnosed with breast cancer between 2016-2017 were reviewed. The review of the histological data was the essence of this study. Both core needle biopsies (CNB) and excisional biopsies (EB) were reviewed. Inclusion criteria included all female patients diagnosed with breast cancer who underwent both diagnostic CNB and EB whose histochemical status was tested in both specimens.
The hormonal status of estrogen receptors (ER), progesterone receptors (PgR) and Her2 were evaluated immunohistochemically.
Equivocal HER2 status was reassessed using Fluorescence in situ hybridization (FISH) test. Validation performed by comparing our laboratory's results with a specialist hospital assay that has been appropriately validated.
Concordance levels were 95%. Equivocal cases were not included in Her2 validation.

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in disease pattern increasing the prevalence of breast cancer [1].
To be able to establish the histological diagnosis that impacts on treatment outcomes, adequate tissue biopsy is mandatory.
Excisional biopsy certainly provides larger tissue samples which allow the pathologist to work with ease in reaching a diagnosis, however, it may necessitate general anesthesia, open surgical procedure and delayed further management. Furthermore, a second procedure may lead to architectural distortion of the surgical field leading to a higher incidence of incomplete excisions.
The growing demand for prognostic information in determining the receptor status preoperatively is considered a corner stone in modern multidisciplinary treatment. Given the available numerous improved types of with the efficiency, cost effectivity and the adequate tissue yield, promotes the diagnostic accuracy on HR status assessment [2][3][4][5][6]. The importance of assessing the HR status is well demonstrated in evaluating molecular subtypes, ER, PgR, and HER2 status in breast cancer. Estrogen receptor remains a powerful predictive factor for response to endocrine treatment and long-term outcome. Similarly, HER2 overexpression has been associated with worse prognosis in patients with newly diagnosed breast carcinoma [8]. In some cases where the inherent Ki67 heterogeneity in ER+/HER2-diagnosed breast tumors, distinguishing the molecular subtypes maybe difficult in the CNB specimens. In such cases, reliability on excisional biopsy is recommended [9]. The receptor status is significantly associated with treatment and monitoring in advanced disease. [10] The liberal use of chemotherapy as neoadjuvant treatment by many oncologists was reported to change the tumor profile and baseline receptor status [11]. Imaging guided biopsy has also proven its reliability with acceptable concordance of the receptor status between surgery and ultrasound-guided CNB [12]. In this review, ER concordance rate in our study was 86%. Four patients were found to be positive in CNB and negative in the subsequent excisional only one was patient found to be positive on excision, while there was no reactivity in CNB. Similarly, PgR concordance rate was 80%. The discordance was only in 7 patients who were initially reported as positive in CNB and were negative in EB although the concordance rate of ER and PgR is within the acceptable range, it may falsely miss a significant number of patients. [2][3][4][5][6] For this reason, it is recommended to reevaluate the HR status in surgically excised specimens. This discrepancy can partly be explained by the known effect of neoadjuvant chemotherapy as shown in 5 of our patients.
We believe it is due to tumor heterogeneity, which has aslo been documented by other authors. It was also noted that Her2 results demonstrated more significant concordance rate of 94% this is probably due to the more robust criteria for identifying HER2 immunostaining in addition to the role of FISH in equivocal cases.

Conclusion
The accuracy of the status in is of paramount importance for both prognosis and treatment. Caution in result interpretation by experienced pathologists may impose significant accuracy and eliminate the false positive results.

Limitation of the Study
This is a small sample to draw firm conclusions, a larger series is required in future studies.