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Histological grade concordance between diagnostic core biopsy and

corresponding surgical specimen in HR-positive/HER2-negative breast
carcinoma

Article  in  British Journal of Cancer · April 2014

DOI: 10.1038/bjc.2014.143 · Source: PubMed

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Original Article

Histologic grading concordance in core biopsy is dependent on tumor

heterogeneity and aggressive biology

C. Daveau (2), S. Baulies (1), M. Lalloum (1), I. Melonio (1), M.A. Bollet (2), B Sigal-

Zafrani (3), X. Sastre (3), A. Vincent-Salomon (3), Anne Tardivon (4), F. Thibault (4),

R. Rouzier (1), C. Malhaire (4), P. Mallon (1), F. Reyal (1)

(1) Department of Surgery, Institut Curie, Paris, France

(2) Department of Radiation Oncology, Institut Curie, Paris, France

(3) Department of Tumor Biology, Institut Curie, Paris, France

(4) Department of Radiology, Institut Curie, Paris, France

Corresponding author

Dr. Fabien Reyal

Department of Surgery

Institut Curie, 26 rue d’Ulm

75005 Paris

Fabien.reyal@curie.net

1
ABSTRACT

Background: Neoadjuvant treatment represents an opportunity to treat subclinical

metastasis, to monitor “in vivo” treatment-sensitivity of the tumor and, to conserve

the breast in the case of good tumor response Patient selection for neoadjuvant

chemotherapy requires that prognostic and predictive factors are available from non-

surgical diagnostic tumor samples. Core needle biopsy is considered an accurate

method to diagnose breast cancer providing an important pathological information.

However, several discordances can be established between core biopsy and

surgical specimen results. Our study aimed to evaluate the histological grade

correlation between these two tissue samples according to tumor subtypes and to

settle the impact of the possible discrepancy in adjuvant treatment .

Patients and methods: A retrospective study was conducted at the institut Curie

between January 2008 and December 2009. Factors that predisposed to histological

grade discordance between core biopsies and surgical specimens were studied. The

impact of this discordance on the systemic treatment decision making process was

evaluated, particularly in hormone receptor-positive tumors because as they were

considered to be the most influenced by histological grade. Kappa coefficient was

calculated to compare the concordance between both groups.

Results: The histological grade correlation in the ER+/Her2-, Her2+ and Triple

negative groups was good (Kappa 0.59, 0.6, 0.69, respectively). Tumor size

measured either by physical examination (0=0.02) or ultrasound (p=0.007),

menopause (p=0.005) and the type of core biopsy (p=0.04) resulted as potential risk

factors for tumor grading error in the ER+/Her2- subgroup. The greatest discordance

rate was found in tumors that had already and indication for adjuvant chemotherapy.

2
Conclusions: Histologic grade discrepancy is correlated with tumor heterogeneity

and tumor size. However, it does not appear to modify the therapeutic decision as it

usually occurs in tumors that already have an indication for adjuvant treatment.

Key Words: breast cancer, neoadjuvant chemotherapy, histologic grade, tumor

heterogeneity, predictive factors.

3
INTRODUCTION

Neoadjuvant treatment setting is currently being used in patients with advanced

disease but also increasingly in the patients initially amenable to conservative

surgery but presenting breast cancers with aggressive pathological features (high

grade, high proliferation, triple negative, HER2 positive) or large hormone receptor

positive breast carcinomas. The clinical benefits are supported by: a) an increase

rate of breast conserving surgery, b) a similar prognosis of breast cancer versus an

adjuvant therapy regimen, c) an accumulation of evidences showing a strong

correlation between achieving a pathological complete response (pCR) after

neoadjuvant chemotherapy (NAC) and a good prognosis in specific subgroups (1-4).

Beyond clinical benefit, the neoadjuvant setting represents an opportunity to study

and monitor “in vivo” treatment-sensitivity of the tumor and to evaluate selection or

resistance acquisition processes.

Because of the great heterogeneity of breast cancer, not all tumors equally respond

to NAC but present different patterns of sensitivity to chemotherapy. Theoretically,

the identification, validation and application of suitable predictive and prognostic

factors will help to ensure that only those patients likely to benefit will receive a

appropriate (systemic?) treatment.

Most predictive and prognostic factors are determined by tumor biology itself.

Besides, selection of patients for NAC requires that all this information is available

from non-surgical diagnostic tumor samples. Core needle biopsy has become the

routine diagnostic method for breast cancer that has replaced fine needle aspiration

cytology as it can provide important additional pathological information for making

decisions regarding systemic therapy (5-10). When a completed pathological

response is achieved, the core biopsy specimen is the only sample to evaluate

4
prognostic and predictive markers. The main limitation of core biopsy is the relatively

small sample of tumor tissue making these markers difficult to study.

One of the classical well-established prognostic factors in breast cancer is

histological grade, that represents the morphological assessment of tumor biological

characteristics. Several studies have reported that the assessment of grade on

needle core biopsy is a strong predictive factor of response to NAC, independently of

the type of regimen used (11-14).

But the selection of representative samples can be difficult due to the existence of a

peri or intratumoral heterogeneity, that often is not taken into consideration (15). This

type of heterogeneity makes histological grade in core biopsies imprecise as a

prognostic factor and is likely the cause of the discrepancy of results obtained in the

literature where histologic grade concordance rate between core biopsy and surgical

excision specimen ranges from 59% to 91% (16-19). The largest study, published in

2003 by Harris et al. found in 500 patients a concordance rate of 67%. The grade in

core biopsy was more underestimated than overestimated and mitotic index had the

highest rate of discordance with an underestimation of 35% (20). Rakha et al

concluded in an overview of the assessment of predictive and prognostic factors in

pretherapeutic biopsies that core biopsy grade is lower, especially due to

underestimation of mitotic index. This may potentially exclude patients that would

benefit from NAC (21).

The question then is whether the tissue from a diagnostic core biopsy reflects the

histological features and the overall biological profile of the tumor. The present study

aimed to evaluate and compare the correlation of histopathological grading of

invasive breast carcinoma core biopsies and subsequent surgical samples according

to molecular subtypes. We analyzed in detail the different factors for tumor grading

error in the hormone receptor-positive patients subgroup in which the decision to

5
give or not systemic treatment may be influenced by histopathological microbiopsy

results.

Hypothetical treatments according to the result of core biopsy were established and

related to the treatment that patients actually underwent in order to evaluate the role

of histological grade as support tool in deciding neoadjuvant chemotherapy.

PATIENTS AND METHODS

The medical records and pathologic reports of all patients who had both a core

biopsy for invasive breast carcinoma and a surgical excision of the tumor at the

Institut Curie, Paris, between January 2008 and December 2009 were reviewed.

Only invasive ductal carcinomas were included in our study. Patients who underwent

neoadjuvant treatment (chemotherapy, hormonal therapy or radiotherapy),

multicentric and multifocal tumors and patients with personal history of other cancer

were excluded.

Clinical, radiological and pathological data such as patient age, menopausal status,

clinical and ultrasound tumor size assessment, lymph node involvement, histological

tumor grade, estrogen receptor, progesterone receptor and Her2/neu status were

collected through a retrospective review of medical and pathological records.

At our Institution all breast cancer cases are pathologically confirmed by either

stereotactic or ultrasound-guided core biopsy, using a 11-gauge or 14-gauge

automated needle, respectively . Core biopsies are then fixed in formalin, paraffin

embedded, and processed according to standard protocol.

6
Histological and immunohistochemical study

Histological tumor grade

The histological grade (HG) was scored for tubule formation, nuclear pleomorphism

and mitotic count. Mitotic Index was assessed on histological sections stained by

Hematoxylin and Eosin. The criteria of Van Diest et al. was used to define mitotic

figure (22, 23). It corresponded to the mitotic score defined in the Nottingham grade;

the number of mitoses observed in 10 consecutive high power fields (HPF) using a

microscope with a 40x objectives and a 10x ocular was counted. Cut-off of <10, 10-

19 and ≥20 mitosis was used to define low, intermediate and high mitotic indexes,

respectively. Overall final tumoral grade was scored according to the Elston and Ellis

modification of the Scarff-Bloom-Richardson grading system (24).

Estrogen receptor (ER) and Progesterone receptor (PR) status.

After rehydration and antigenic retrieval in citrate buffer (10 mM, pH 6.1), the tissue

sections were stained for estrogen receptor (ER) (clone 6F11, Novocastra, 1/200),

and progesterone receptor (PR) (clone 1A6, Novocastra, 1/200). Revelation of

staining was performed using the Vectastain Elite ABC peroxidase mouse IgG kit

(Vector Burlingame, CA) and diaminobenzidine (Dako A/S, Glostrup, Denmark) as

chromogen. Positive and negative controls were included in each slide run. Cases

were considered positive for ER and PR according to standardized guidelines using

a cut-off of ≥10% stained tumor nuclei (25, 26).

HER2 status.

After rehydration and antigenic retrieval in citrate buffer (10 mM, pH 6.1), the tissue

sections were stained for HER2 (clone CB11, Novocastra, 1/1000). Revelation of

7
staining was performed using the Vectastain Elite ABC peroxidase mouse IgG kit

(Vector Burlingame, CA) and diaminobenzidine (Dako A/S, Glostrup, Denmark) as

chromogen. Positive and negative controls were included in each slide run. The

determination of HER2 overexpression was determined according to GEFPICS

guidelines with FISH performed in all cases of HER2 2+ result (27).

Definition of tumor subtypes

Immunohistochemistry features of each tumor subtype were applied. Patients were

categorized as ER positive/Her2 negative, HER2 positive and triple-negative (ER

negative/PR negative/Her2 negative).

Statistical analysis

The description of quantitative variables was performed using median and range

(minimum-maximum). The qualitative variables were presented by means of the

description of proportions. Comparison was done between the core biopsy results

and the final histology from surgical specimens. Baseline characteristics were

compared using Chi-square or Fisher's exact tests for categorical variables and

Student's T-tests for continuous variables. All tests were two-sided and the

significance level was set at 0.05.

To study the agreement Cohen’s Kappa coefficient was used. Complete agreement

is considered as Kappa equal to 1. Kappa values close to or less than 0 show poor

agreement. An absolute concordance rate was calculated for all three corresponding

grades. Kappa was also calculated for each grading system separately (tubule

formation, nuclear pleonorphism, mitotic index and Elston&Ellis grade).

8
RESULTS

A total of 350 consecutive biopsies were assessed and compared to surgical

specimens. Immunophenotyping showed that ER or PR were positive in 299 cases

(85.3%), HER2 was overexpressed in 29 (8.3%) and 22 cases (6.3%) resulted to be

triple negative tumors.

We wanted to evaluate whether the assessment of histological grade on core biopsy

can provide information to support neoadjuvant treatment decision making. We

focused our analysis in hormone receptor-positive subgroup where the decision

making process is the most influenced by histological grade. HER2-positive and

triple negative tumors will receive almost systematically chemotherapy.

ER+/HER2- subgroup

The median number of core biopsies per patient was 3 (1-11) and the median

minimum sample size was 7mm (range 1-22). The median maximum size was 12mm

(range 3-30)..

Patient and tumor characteristics are detailed in Table 1. From this group, 67% core

biopsies were performed under ultrasound guidance.

Descriptive data of Elston-Ellis tubule formation, nuclear polymorphism, mitotic index

and overall histological grade score obtained from core biopsies and surgical

specimens are showed in Table 2.

The global concordance rate for overall HG between the two sample types was 75%

(224 patients), Kappa 0.59. Analyzing grades separately, 78% in grade I, 68.4% in

grade II and 95% in grade III (Table 3).

In the 75 cases with discordance (25%), histologic undergrading was found in 55

patients (73.3%, 18.4% of all cases) and overgrading in 20 cases (26.7%, 6.7% of all

9
cases). Global misgrading did not differ by more than a factor in 73 cases (97.3%,

24.4% of all cases). No tumor scored grade III on biopsy was reclassified grade I on

the surgical specimen and only 2 cases grade I by biopsy were finally identified as

grade III (2.2% of grade I cases). Test de Mac Nemar pour savoir si plus de

surclassifaction ou sousclassification ?

Regarding tubule formation, nuclear pleomorphism and mitotic index, the

concordance rate was 75% (Kappa 0.56), 66.5% (Kappa 0.41) and 74.6% (Kappa

0.44), respectively. An overestimation of the grade was related to an overestimation

of nuclear pleomorphism (50 cases, 16.7% of all cases), whereas its underestimation

was mainly due to the underestimation of mitotic index (70 cases, 23.4% of all

cases).

In order to assess the role of HG as a predictive factor for neoadjuvant

chemotherapy decision making in this subgroup, potential factors for tumor grading

error were studied (Table 4). A non concordant grade was found more frequently in

premenopausal patients (36.8% vs 20.7%, p=0.005), in no ultrasound-guided

biopsies (32.3% vs 21.5%; p=0.04) and in larger tumors, measured by both phyisical

and ultrasound examination (p=0.02 and p=0.007, respectively). There were no

statiscally significant differences in number, minimal and maximal size of core

biopsies.

Table 5 shows all data related to factors that might increase the risk of

misclassification of mitotic index. No multivariate model was identified to correct the

discrepancy of these variables, most likely due to the strong interaction among them.

With an hypothetical view to maximally reduce neoadjuvant chemotherapy treatment

in ER+Her2- patients, we analyzed grade II and III jointly versus grade I. The

concordance rate was 87.3% (261 cases) and underestimation was achieved in 20

cases (6.7%) (Table 6). Kappa value was 0.69 which indicated substantial

10
agreement. The fact we jointly analized grade II/III improved consistency in relation

to a separate analysis (Kappa 0.69 versus 0.59) (pas clair). No factors were found to

influence the risk of misclassifying (Table 7).

Triple negative and HER2+ subgroups

Twenty-two patients (6.3%) were triple negative tumors and 19 cases (86.34%) had

Grade III score. Overall concordance rate for HG was 91% (Kappa 0.69) and

discrepancy was found in cases of grade II (2 grade II in biopsy resulted to be grade

III in postoperative specimen), not in grade III.

Twenty-nine Her2 positive tumors were identified (8.3%), 19 cases (65.5%) had

grade III and the concordance rate was 79.3% (Kappa 0.6). As in Triple negative

tumors, all grade III cases were correctly scored on core biopsy, and disagreement

was found in those cases scored grade II on biopsy.

We can conclude that concordance rates resulted to be higher in these two tumors

subgroups and in case of discordance, undergrading on core biopsy was found in all

cases and the difference was never more than one grade (Table 8),

Consequences on treatment recommendations

We retrospectively investigated whether grading discrepancy could change the

decision of systemic treatment in the ER+/HER2- group. Hypothetical treatments

according to the result of core biopsy were established and related to the treatment

that patients actually underwent after the result of the surgical specimen. This

substudy was not performed in triple negative and Her2 positive tumors because

such information is not useful in terms of therapeutic decision in these groups as

there is almost always an indication of adjuvant chemotherapy (Table 9).

11
In ER+/Her2- group, 127 patients (42.5%) received chemotherapy, 146 hormone

therapy (48.8% c’est tout ?) and 26 patients (88.7% sort d’où ?) had no indication of

adjuvant therapy.

Discordance of HG according to the recommended postoperative treatment;

chemotherapy, hormone therapy and no adjuvant treatment was 37.8% (48 cases),

17.8% (26 cases) and 11.5% (3 patients), respectively (p<0.05). We found a greater

discordance rate in the chemotherapy group, and it was related to an

underestimation in presurgical grade (93.7%).

Hypothetical changes in treatment were identified only in 7 cases (2.34%): 6 patients

(2%) who underwent adjuvant chemotherapy postoperatively were supposed to

receive initially hormone therapy exclusively according to biopsy results and 1

patient (0.34%) who finally was treated with hormone therapy, was originally

scheduled to receive chemotherapy. No changes in treatment recommendations

before and after surgery were identified among patients who did not have an

indication of adjuvant therapy,

DISCUSSION

Breast cancer treatment has become more complex over time. Surgical and

chemotherapeutic options have increased in recent years and the accuracy of

prognostic information should increase in importance as many decisions are based

on these data. Clinicians need to obtain the information from core biopsy to identify

patients with good prognosis tumors as well as patients who are most likely to

respond to chemotherapy. Several prognostic factors are used in breast cancer

management and in therapeutic decision as clinical tumor size, histological type,

lymph node involvement, hormonal and HER2 status and tumor grading.

12
Our study was undertaken to assess the relationship between the tumor grading

obtained from core biopsy samples and from surgical specimens of the same tumor.

We found that the concordance rate for histological grade in ER+/Her2-, triple

negative and Her2+ tumors was 75%, 91% and 79.3%, respectively. A lower

discrepancy was observed in tumors with a higher histologic grade. These findings

corroborate the observations of Harris et al. who found a higher concordance in

grade III tumors (84% in grade III versus 60% grade I/II) (20). Concordance for ER,

PR and HER2 status was not studied since we did not have this information from

initial core biopsies. But, several studies have showed high concordance rates for

ER, PR and Her2 status between the core biopsy and excisional specimen (7, 28-

32).

It is important to identify the different factors associated with histological grading

concordance, as core biopsy grade tends to be lower, particularly due to

underestimation of mitotic index (20, 28, 29, 33). Kappa statistics indicated a good

agreement in tubule formation and global HG, while Kappa value for nuclear

pleomorphism and mitotic index was poorer.

In our series, 55 (18.4%) were undergraded, but few cases differed more than one

grade (only two tumors classified as grade I on biopsy were subsequently

reclassified as grade III, and all grades III on biopsy were reconfirmed later on

postoperative specimen). When we analyzed grade II and III jointly versus grade I

the concordance rate increased (87.3% of all cases) and underestimation was lower

(6.7% of all cases), Kappa value showed a stronger correlation (Kappa 0.69).

Such underestimation is due to the inherent undersampling in core biopsy

procedure. This tissue may not include the growing edge of the tumor, therefore,

formal counts of mitotic figures can not be assessed. Furthermore, breast carcinoma

is known for its heterogeneity in relation to mitotic index. Morris et al. showed that

13
histological heterogeneity between the periphery and the center of the tumor was

found in 29% (15). It would be in accordance with our results, where smaller tumors

presented greater concordance, since the larger the tumor is, the greater

heterogeneity presents and more likely to have unrepresentative samples.

All these studies concluded that several samples of the same tumor should be

studied in order to achieve a reliable score of histologic grade. However in our study,

the only independent factors associated with discordance were premenopausal

status, tumor size and the type of core biopsy performed. We found no differences in

the number or size of the core biopsies. These results are in agreement with those

published by Leary O et al. In a series of 113 patients, they showed that the number

and size of biopsies did not influence the concordance between preoperative and

postoperative histopathology reports (34). In contrast, a short report published by

McIlenny et al. found that a single core biopsy was only 32% accurate in predicting

the grade while this rate rose to 74% for four core biopsies (p=0.001) (35).

Prognostic factors in ER+/Her2- group are really important in order to prescribe

adjuvant systemic treatment or neoadjuvant chemotherapy. The greatest

discordance rate was found in the subgroup that had already and indication for

adjuvant chemotherapy (37.8% in chemotherapy group, 17.8% in hormone therapy

group and 11.5% in untreated group). A likely explanation is because they have a

more aggressive tumor biology and have higher tumor heterogeneity. This

discrepancy did not have a therapeutic impact because systemic treatment decision

making also integrates other variables such as tumor size, nodal involvement, age of

patient and proliferation.

From the present study we can conclude that histologic grade discrepancy is

correlated with the tumor heterogeneity and tumor size. However, it does not appear

14
to modify the therapeutic decision as it usually occurs in tumors that already present

an indication of adjuvant treatment.

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19
Tables and Figures

Table 1. ER+/HER2- patients: Clinical and pathological characteristics

299 Cases (%)

ER positive (IHC>10%) 299 (100)
Her2 negative 299 (100)
Menopausal status 222 (74.2)
Median clinical tumor size (mm) 10 (0-100)
Ultrasound guided biopsy 200 (67)
Median ultrasound tumor size (mm) 12 (3-100)

20
Table 2. Pathological results in core biopsies and surgical specimens in ER+/Her2-

Core Biopsy Cases (%) Surgical Specimen Cases (%)

Tubule formation
I 30 (10) 37 (12.4)
II 107 (35.8) 102 (34.1)
III 162 (54.2) 160 (53.5)
Nuclear pleomorphism
I 23 (7.7) 27 (9)
II 145 (48.5) 137 (45.8)
III 131 (43.8) 135 (45.2)
Mitotic Index
I 241 (80.6) 189 (63.2)
II 33 (11) 55 (18.4)
III 25 (8.4) 55 (18.4)
Elston and Ellis Grade
I 91 (30.4) 89 (29.8)
II 168 (56.2) 135 (45.2)
III 40 (13.4) 75 (25.1)

21
Table 3. Concordance rate for histological grade in ER+/Her2- group

299 Invasive Ductal Carcinoma cases

ER+/Her2-
Core biopsy Surgical specimen Kappa
Tubule formation I II III
I 22 7 1 0.56
II 14 68 25
III 1 27 134
Nuclear pleomorphism I II III
I 8 13 2 0.41
II 17 93 35
III 2 31 98
Mitotic index I II III
I 185 37 19 0.44
II 3 16 14
III 1 2 22
Global Elston-Ellis Grade I II III
I 71 18 2 0.59
II 18 115 35
III 0 2 38
Absolute concordance 224 (75%) No concordance 75 (25%)

22
Table 4. Factors associated with risk of grade misclassification
US: ultrasound
T: tumoral
Bmin: Biopsy minimum
Bmax: Biopsy maximum

299 Invasive Ductal Carcinoma cases

ER+/Her2- (%)
No concordance Concordance p
Menopausal status 0.005
No 28 (36.8) 48 (63.2)
Yes 46 (20.7) 176 (79.3)
Ultrasound guided biopsy 0.04
No 32 (32.3) 67 (67.7)
Yes 43 (21.5) 157 (78.5)
Median US T size (mm) 14 (5-50) 12 (3-100) 0.007
Median clinical T size (mm) 15 (0-90) 10 (0-100) 0.02
Median biopsy number 3 (1-11) 3 (1-9) NS
Median Bmin size (mm) 8 (1-22) 7 (1-22) NS
Median Bmax size (mm) 12 (5-22) 12 (3-30) NS
Total 75 (25) 224 (75)

23
Table 5: Factors associated with risk of mitotic index misclassification
US: ultrasound
T: tumoral
Bmin: Biopsy minimum
Bmax: Biopsy maximum

299 Invasive Ductal Carcinoma cases

ER+/Her2- (%)
No concordance Concordance p
Menopausal status 0.01
No 27 (35.5) 49 (64.5)
Yes 48 (21.6) 174 (78.4)
Ultrasound guided biopsy 0.0001
No 40 (40.4) 59 (59.6)
Yes 36 (18) 164 (82)
Median US T size (mm) 15 (5-50) 11 (3-100) 7.7e-6
Median clinical T size (mm) 20 (0-90) 10 (0-100) 7.1e-2
Median biopsy number 2 (1-11) 3 (1-9) 1.1e-2
Median Bmin size (mm) 10 (1-22) 6.5 (1-22) 1.2e-2
Median Bmax size (mm) 12 (5-30) 12 (3-30) 5e-2
Total 76 (25.4) 223 (74.6)

24
Table 6: Concordance rate in Grade I versus Grade II/III

299 Infiltrating Ductal Carcinoma cases ER+/Her2-

Core Biopsy Surgical specimen
Elston&Ellis Grade Grade I Grade II/III Kappa
Grade I 71 20 0.69
Grade II/III 18 190
Concordance 261 (87.3%) No Concordance 38 (12.7%)

25
Table 7. Factors associated with risk of grade misclassification (grade I versus II/III)

299 Invasive Ductal Carcinoma cases

ER+/Her2- (%)
No concordance Concordance p
Menopausal status NS
No 12 (15.8) 64 (84.2)
Yes 26 (11.7) 196 (88.3)
Ultrasound guided biopsy NS
No 9 (9.1) 90 (90.9)
Yes 29 (14.5) 171 (85.5)
Median US T size (mm) 12.5 (5-27) 12 (3-100) NS
Median clinical T size (mm) 10 (0-70) 10 (0-100) NS
Median biopsy number 3 (1-7) 3 (1-11) NS
Median Bmin size (mm) 5 (1-22) 7 (1-22) NS
Median Bmax size (mm) 12 (5-22) 12 (3-30) NS
Total 38 (12.7) 261 (87.3)

26
Table 8. Concordance rate for histological grade in Triple negative and HER2+
patients

22 Infiltrating Ductal Carcinoma cases

Triple Negative
Core Biopsy Surgical specimen
Elston&Ellis Grade Grade I Grade II Grade III Kappa
Grade I 0 0 0
Grade II 0 3 2 0.69
Grade III 0 0 17
Concordance 20 (91%) No Concordance 2 (9%)

29 Infiltrating Ductal Carcinoma cases

Her2+
Core biopsy Surgical specimen
Elston&Ellis Grade Grade I Grade II Grade III Kappa
Grade I 0 1 0
Grade II 0 9 5 0.6
Grade III 0 0 14
Concordance 23 (79.3%) No Concordance 6 (20.7%)

27
 Table 9. Changes in the recommended treatment due to grading discrepancies
between core biopsies and surgical specimens in ER+/HER2- subgroup

299 Invasive Ductal Carcinoma cases

ER+/Her2- (%)
Postsurgical 299 No Grading Grading Pre- Pre- Treatment
Treatment (100) Discrepancy Discrepancy surgical surgical changes
Grade Grade
Over- Under-
Estimation Estimation
Chemotherapy 127 79 (62.2) 48 (37.8) 3 (6.3) 45 (93.7) 6 HT (2)
(42.5)
Exclusive 146 120 (82.2) 26 (17.8) 15 (57.7) 11 (42.3) 1 ChT
hormone (48.8) (0.35)
therapy
No adjuvant 26 23 (88.5) 3 (11.5) 2 (66.6) 1 (33.3) 292 NoT
systemic (8.7) (97.65)
therapy

HT: Hormone therapy

ChT: Chemotherapy

NoT: no treatment changed

28

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