Biopathologic profile of breast cancer core biopsy: is it always a valid method?

doi:10.1016/j.canlet.2004.07.041

Cancer Letters

Volume 218, Issue 1, 31 January 2005, Pages 117-121

https://doi.org/10.1016/j.canlet.2004.07.041 Get rights and content

Abstract

For breast cancer management biopathologic profile and particularly the expression of estrogen receptor (ER) and progesterone receptor (PR) is considered essential. In advanced cases, core biopsy results are the only data available. To evaluate reliability of data, results of ER, PR, MIB1, p53 and c-erbB2 on core biopsy were compared with those on surgical specimens. Results showed a statistically significant concordance for ER and PR in pT1 but not in pT2 tumors, possibly due to breast cancer heterogeneity. MIB1 results were worse with no significant concordance even for pT1 group. There was statistically significant concordance in pT1 and pT2 groups for p53 and c-erbB 2, probably due to the high number of negative cases for these markers. We recommend more core biopsies for larger tumors since core biopsy has a high probability for giving unreliable data in these cases.

In conclusion, this study showed that core biopsy has a high probability for not very reliable data in bigger tumors where the results obtained migth be the only data available. A higher number of core biopsy is recommended in those cases.

Introduction

Over the last years, the role of core biopsy has become well established and widely used in routine preoperative practice since it provides a reliable method for a careful histopathological diagnosis of breast cancers which is essential for correct surgical management of breast diseases [1], [2], [3], [4]. However, recently, in addition to the histopathological diagnosis, clinicians increasingly demand that the pathologist gives a biopathologic profile and in particular the determination of estrogen receptor (ER) and progesterone receptor (PR) for timely patient management. In fact, knowledge of the receptor status and particularly the expression of ER is usually considered essential for planning the management of the disease and in some cases, such as advanced disease, the results obtained from the core biopsy specimen may be the only data available for diagnosis and determination of hormone receptor status before medical treatment. Since there are only a few studies on the biopathological characterization of breast cancer with core biopsy [5], [6], we decided to compare the results of ER, PR, MIB1, p53 and c-erbB2 obtained on core biopsy with the corresponding results obtained on excised surgical specimens.

Section snippets

Materials and methods

Consecutive cases of 68 breast carcinomas, observed at the Institute of Pathological Anatomy and Histology, Perugia University, Italy, for which both core biopsy and excised surgical specimens were available entered this study. Patients who received preoperative chemotherapy or radiation therapy were excluded. All core biopsies were carried out with an 18-gauge biopsy needle. For each case, 2–6 (mean 3.3) core biopies were taken. Core biopsy and surgically resected samples were fixed in

Results

Table 1 gives the morphologic subtypes of the 68 tumors. The mean age of patients was 56.8 years (range 38–83 years). The excised surgical breast cancers were pT2 in 26 cases and pT1 in 42 cases. This last group comprised 31 pT1c breast cancers and 11 cases either pT1a or pT1b which were considered together owing to the relatively small number (Table 2). As regards ER and PR, the average nuclear area examined for each case was 26,992 μm² (range 12,549–106,497) for ER and 34,799 μm² (range

Discussion

The presence of ER and PR in breast cancer cells represents a relatively weak prognostic marker, but is a strong predictive factor for response to hormonal therapy [11], [12], [13], [14], [15]. In recent years, direct immunohistochemical visualization of ER and PR by monoclonal antibodies has become a widely used method for determining receptor content using immunocytochemical methods (ICA) on frozen sections and more recently on paraffin sections, also evaluated by computer assisted image

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Cited by (37)

Non-histopathological parameters associated with upgrade of breast tumours yielding a core biopsy report of histological grade 2 ductal no special type to grade 3 on excision
2018, European Journal of Surgical Oncology
The aim of the study was to identify clinical, radiological and immuno-histochemical factors that may help predict upgrade of invasive ductal cancers of no special type (IDC-NST) with a core biopsy grade of 2 to grade 3 on final histology.
A prospectively maintained database of ultrasound visible solid masses was used to identify lesions yielding a core biopsy result of IDC-NST grade 2 who underwent immediate surgery yielding a grade 2 or grade 3 tumour. Associations were sought between the source of patient (screening/symptomatic), core biopsy receptor status and imaging findings and the grade of the excision specimen tumour. Statistical analysis, which included the chi-squared test, ROC curves and Cox regression analysis, was used to compare upgrade vs no upgrade for each factor.
463 IDC-NST breast cancers of core biopsy grade 2 gave 344 grade 2 and 119 grade 3 tumours at excision. Factors significantly associated with upgrade were large ultrasound (US) size, hyperechogencity, stiffness at shearwave elastography (SWE), calcification on mammography and oestrogen receptor (ER) and progesterone receptor (PR) negativity. Patient source, Human epidermal growth factor receptor 2 (HER-2) status, ultrasound (US) distal effect and mammographic spiculation were not significantly associated with chance of upgrade. On multivariate analysis, only US size maintained statistical significance.
Oncologists and surgeons should be aware that lesions with a core biopsy diagnosis of grade 2 IDC-NST measuring over 15 mm on US have a 37% chance of being grade 3 on excision and this should be considered when deciding pre-operative management.
Impact of molecular subtypes classification concordance between preoperative core needle biopsy and surgical specimen on early breast cancer management: Single-institution experience and review of published literature
2017, European Journal of Surgical Oncology
Core needle biopsy (CNB) plays a crucial role as diagnostic tool for breast cancer (BC). The characterization of biomarkers status before surgical treatment is crucial when primary systemic therapy is a therapeutic option. The aim of this analysis was to report concordance between preoperative CNB and surgical specimen (SS) in evaluating biomarkers and molecular subtypes.
Data have been collected from a cohort of 101 patients affected by early BC treated at Careggi Florence University Hospital, between January 2014 and March 2015. The conformity between molecular subtype classification was tested using kappa (κ) test.
Mean age was 57.5 years (range 29–86). There was concordance between the estrogen receptor (ER) assessment on CNB and SS in 95 cases (94.1%). Concordance of the progesterone receptor (PgR) assessment was observed in 89 cases (88.1%). Concordance for detecting immunohistochemistry-assessed BC molecular subtypes was 87.1% (κ = 0.78). Concerning Ki-67 evaluation, we report a concordance rate of 88.1% (κ = 0.68). The evaluation of luminal A plus luminal B/HER negative subgroup showed a κ-value of 0.65.
CNB showed good accuracy in evaluating hormonal receptors status, HER2, and BC molecular subtypes. Evaluation of Ki67 status was less accurate than other biomarkers; therefore, we recommend that it should be detected both on CNB and SS samples, especially in hormonal positive HER2 negative tumors, in order to avoid a misclassification of tumor subtypes that could lead to an omission of potential effective systemic therapy.
Impact of host and histopathological factors on the discrepancies in estrogen receptor, and progesterone receptor, and HER2 status between core needle biopsy and surgically excised tumors
2016, Breast
Citation Excerpt :
Therefore, concordance may be dependent on tumor size. Cavaliere et al. [11] reported that large tumors presumably show a higher discrepancy rate in ER and PR status due to heterogeneity in the tumor being missed in the core biopsy. Univariate analysis in our study found that T1b and T1c showed a significantly lower discrepancy rate for ER status (1.1% and 4.4%, respectively) compared to T3 (10.9%) and T4 (8.8%) (p = 0.03).
The high reliability and utility of core needle biopsy (CNB) have been previously described. Our aim in this study was to clarify the host and histopathological factors influencing the discrepancies in ER, PgR, and HER2 status between CNB and surgically excised tumors (SET).
All patients diagnosed with operable invasive breast cancer in our hospital between January 2005 and April 2015 were included in the study; patients who required neoadjuvant chemotherapy were excluded. ER, PgR, and HER2 expression were assessed between paired CNB and SET samples. ER and PgR status were determined using immunohistochemistry(IHC). HER2 status was determined using IHC and scored from 0 to 3+. Fluorescence in-situ hybridization analysis was carried out in HER2 2+ cases. The cut off point for ER and PgR positivity was set at 1%.
A total of 1307 patients were assessed. The concordance rates of ER, PgR, and HER2 status in CNB and SET were 95%, 84% and 97%, respectively. Factors of discrepancy were nuclear grade, histological type, and menopausal status for ER and PgR, and none detected for HER2. The discrepancy factors were assessed with univariate and multivariate analysis.
Using the largest known dataset to date of paired samples from a single institution, we evaluated the accuracy of CNB and the discrepancy factors between CNB and SET in breast cancer patients. We conclude that CNB for ER and PgR assessment in postmenopausal patients before treatment should be used with caution. Further research will contribute to increased CNB accuracy, improving patient treatment decisions.
Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas
2013, Modern Pathology
Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (P<0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.
Cancer Care Ontario Guideline Recommendations for Hormone Receptor Testing in Breast Cancer
2012, Clinical Oncology
Citation Excerpt :
Eighteen comparative studies found concordance values greater than 83% (median 95%) for ER and greater than 69% (median 88.5%) for PR from core biopsies against standard surgical specimens [32–49]. Variability between cores and whole tumours may be dependent on intratumoural heterogeneity or be affected by treatment [37,46]. Tissue microarray (TMA) should not be used for diagnostic purposes.
Hormone receptor testing (oestrogen and progesterone) in breast cancer at the time of primary diagnosis is used to guide treatment decisions. Accurate and standardised testing methods are critical to ensure the proper classification of the patient's hormone receptor status. Recommendations were developed to improve the quality and accuracy of hormone receptor testing based on a systematic review conducted jointly by the American Society of Clinical Oncology/College of American Pathologists and Cancer Care Ontario's Program in Evidence-Based Care. Evidence-based recommendations were formulated to set standards for optimising immunohistochemistry in assessing hormone receptor status, as well as assuring quality and proficiency between and within laboratories. A formal external review was conducted to validate the relevance of these recommendations. It is anticipated that widespread adoption of these guidelines will further improve the accuracy of hormone receptor testing in Canada.
Ultrasound-guided breast interventions
2012, Ultrasound Clinics

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Biopathologic profile of breast cancer core biopsy: is it always a valid method?

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Eur. J. Cancer

Breast

Breast

Surg. Oncol. Clin. N. Am.

Percutaneous large core breast biopsy

Cancer

Needle core biopsy of mammographic lesions

Am. J. Roentgenol.

The role of pre-operative diagnosis in breast cancer

Histopathology

Conversion to core biopsy in preoperative diagnosis of breast lesions: is it justified by results?

J. Clin. Pathol.

Oestrogen and progesterone receptor assessment in core biopsy specimens of breast carcinoma

J. Clin. Pathol.

Estrogen and progesterone receptors in breast cancer: comparison between enzyme immunoassay and computer-assisted image analysis of immunocytochemical assay

Cytometry

Computer-assisted immunocytochemical determination of breast cancer steroid receptors on cytological smears of excised surgical specimens compared with frozen sections

Cytometry