Skip to main content
Erschienen in: Wiener klinische Wochenschrift 17-18/2023

Open Access 03.04.2023 | original article

Axillary lymph node status and invasive lobular breast cancer

Analysis of the Clinical Tumor Register of the AGO Austria

verfasst von: Sabine Danzinger, MD, Karin Pöckl, Gerit Kronawetter, Christian Pfeifer, Sandra Behrendt, Patricia Gscheidlinger, Lois Harrasser, Helmut Mühlböck, Walter Dirschlmayer, Christian Schauer, Roland Reitsamer, Heidemarie Uher, Kristina Schönau, Irmgard Delmarko, Christian F. Singer

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 17-18/2023

Summary

Background

Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register.

Methods

Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824.

Results

A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19–3.14; p = 0.008 and OR 3.22; 95% CI: 1.47–7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC.

Conclusion

The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.
Hinweise

Availability of data and material

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
AGO
Association for Gynecological Oncology
ALN
Axillary lymph node
BC
Breast cancer
BVI
Blood vessel invasion
CI
Confidence interval
DCIS
Ductal carcinoma in situ
ER
Estrogen receptor
HER2
Human epidermal growth factor receptor 2
HR
Hormone receptor
IDC
Invasive ductal carcinoma
ILC
Invasive lobular carcinoma
KTR
Clinical Tumor Register, Klinisches TumorRegister
LVI
Lymphovascular invasion
OR
Odds ratio
PN
Pathological node stage
PR
Progesterone receptor
PT
Pathological tumor stage
SD
Standard deviation
SEER
Surveillance, Epidemiology, and End Results Program

Background

Invasive breast cancer (BC) is considered a heterogeneous disease. After invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) represents the second most common type of invasive BC, comprising up to 15% of all cases [13].
The ILC is characterized by diffuse infiltration of the stroma with a single file pattern. The loss or lack of epithelial E‑cadherin expression represents a characteristic feature of ILC. E‑cadherin mediates cell-cell adhesion and dysregulation results in distinctive discohesive growth patterns observed in ILC. Thus, E‑cadherin antibodies are used to differentiate between lobular and ductal lesions by immunohistochemistry [4, 5].
The ILC distinctly differs from IDC in its clinicopathological characteristics and molecular alterations. Compared to IDC, ILC is more frequently multifocal, multicentric, and bilateral. Many studies show that ILC is associated with a good prognostic phenotype such as positive hormone receptors (HR) (both estrogen and progesterone receptors, ER, PR), human epidermal growth factor receptor 2 (HER2)-negativity, low tumor grade, and a low to moderate proliferation index. Despite these good prognostic properties, invasive lobular tumors are generally diagnosed at a more advanced stage. Furthermore, there is a tendency for late recurrences, and a higher rate of multiple metastases with a variable pattern of involvement of distant sites [3, 618].
The axillary lymph node (ALN) involvement represents one of the most important prognostic factors in early BC [1925]; however, previous studies have shown controversial results regarding the ALN status between ILC and IDC. There are many studies demonstrating that the ALN involvement does not differ between both groups [10, 26, 27]; however, some studies showed an association between ILC and a higher incidence of positive ALN involvement [8, 28, 29]. In contrast, there are studies reporting less frequent ALN positivity in ILC [30, 31]. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register.

Methods

Study population

This was a retrospective study based on data from patients of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO). Women with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were enrolled in the study. Exclusion criteria were patients with both ductal and lobular carcinoma, patients who had neoadjuvant therapy, patients with recurrent disease, and patients with primary metastatic disease. In cases of bilateral BC, both sides were included as separate tumors. Altogether, the analysis was based on 2095 patients (bilateral cancer n = 32), all 2127 tumors were evaluated and compared in 2 groups, ILC n = 303 (14.2%), IDC n = 1824 (85.8%).
The KTR represents a computerized database and cancer register collecting data on breast, endometrial, ovarian, and cervical cancer from hospitals throughout Austria (https://​ktr.​iet.​at). This register is maintained by the Department of Clinical Epidemiology, Tyrolean Federal Institute of Integrated Care, Innsbruck, Austria (https://​www.​iet.​at).
In this study, the following clinicopathological parameters of BC patients were evaluated: age at diagnosis, menopausal status, bilateral cancer, tumor morphology, concomitant ductal carcinoma in situ (DCIS) component, tumor grade, immunohistochemical parameters (ER, PR, HER2, Ki67, ≤ 14% low, 15–40% intermediate, > 40% high), lymphovascular invasion (LVI), blood vessel invasion (BVI), and pathological tumor (pT) stage and pathological node (pN) stage. Additionally, we evaluated the axillary dissection rate, and the total number of lymph nodes removed. Comparisons were then made between patients/tumors divided into two separate histologic subgroups: IDC and ILC.

Statistical analysis

Descriptive statistics were performed to analyze the characteristics of the two histopathological groups (ILC and IDC). The χ2 and Fisher’s exact (for smaller sample sizes) tests were used to investigate the proportions of the clinical histopathological characteristics between ILC and IDC. Logistic regression was performed to identify independent parameters associated with ILC and IDC. Associations were summarized using the odds ratios (OR) and corresponding 95% CI derived from the model estimates. We excluded all unknown or undetermined values from the analysis. Statistical significance was considered at p < 0.05 (two-tailed). We performed all statistical analyses using the statistical software package R version 3.4.1 [32].

Ethics approval

This study was approved by the ethics committee of the Medical University of Vienna (1589/2019). All procedures performed in the study were in accordance with the ethical standards of the institutional committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. According to the ethics committee of the Medical University of Vienna, written informed consent was not required owing to the retrospective design of the study.

Results

Altogether 2095 patients were evaluated in the study. The study population comprised 2 subgroups: 297 patients with ILC (14.2%) and 1798 patients with IDC (85.8%). The characteristics of the patients are summarized in Table 1. The mean age at diagnosis was 65.0 years (standard deviation (SD): 12.4) in patients with ILC compared to 63.0 years (SD: 12.9) in IDC patients (p = 0.01). We found no significant difference in the distributions of age at diagnosis between both groups (p = 0.27). Premenopausal patients were significantly more common in the IDC (n = 402, 22.4%) compared to the ILC group (n = 49, 16.5%) (p = 0.03). Bilateral BC was diagnosed in 32 (1.5%) patients; bilateral cancers did not differ between the groups (p = 0.62).
Table 1
Characteristics of the patients and tumors
Patientstotal (n=2095)
ILC (n=297)
IDC (n=1798)
p‑value a
Age at diagnosis (years)
Mean (SD)
65.0 (12.4)
63.0 (12.9)
0.01
n
%
n
%
20–39
4
1.3
44
2.4
0.27
40–59
100
33.7
684
38.0
60–79
159
53.5
888
49.4
80–99
34
11.4
182
10.1
Menopausal status
Premenopausal
49
16.5
402
22.4
0.03
Postmenopausal
229
77.1
1289
71.7
Unknown
19
6.4
107
6.0
Bilateral BC
Yes
6
2.0
26
1.4
0.62
No
291
98.0
1772
98.6
Tumorstotal (n=2127)
ILC (n=303)
IDC (n=1824)
n
%
n
%
p‑value a
DCIS component
Yes
67
22.1
915
50.2
<0.001
No
236
77.9
905
49.6
Unknown
0
0.0
4
0.2
Tumor grade
1
29
9.6
399
21.9
<0.001
2
218
71.9
995
54.6
3
51
16.8
418
22.9
Unknown
5
1.7
12
0.7
ER
Positive
298
98.3
1529
83.8
0.001
Negative
4
1.3
100
5.5
Unknown
1
0.3
195
10.7
PR
Positive
255
84.2
1399
76.7
0.50
Negative
47
15.5
226
12.4
Unknown
1
0.3
199
10.9
HER2
Positive
15
5.0
228
12.5
<0.001
Negative
282
93.1
1576
86.4
Unknown
6
2.0
20
1.1
Ki67
Low
158
52.1
670
36.7
<0.001
Moderate
122
40.3
684
37.5
High
18
5.9
244
13.4
Unknown
5
1.7
226
12.4
LVI
Yes
56
18.5
348
19.1
0.97
No
230
75.9
1402
76.9
Unknown
17
5.6
74
4.1
BVI
Yes
6
2.0
33
1.8
0.88
No
247
81.5
1622
88.9
Unknown
50
16.5
169
9.3
pT stage
pT0
0
0.0
0
0.0
<0.001
pTis
0
0.0
0
0.0
pT1
170
56.1
1332
73.0
pT1mic
1
0.3
13
0.7
pT1a
10
3.3
97
5.3
pT1b
39
12.9
393
21.5
pT1c
120
39.6
829
45.4
pT2
98
32.3
436
23.9
pT3
29
9.6
35
1.9
pT4
5
1.7
18
1.0
pT4a
0
0.0
2
0.1
pT4b
5
1.7
16
0.9
pT4c
0
0.0
0
0.0
pT4d
0
0.0
0
0.0
pTX
1
0.3
3
0.2
pN stage
pN0
200
66.0
1235
67.7
<0.001
pN0
198
65.3
1224
67.1
pN0 (i+)
2
0.7
11
0.6
pN1
54
17.8
429
23.5
pN2
24
7.9
75
4.1
pN2a
23
7.6
74
4.1
pN2b
1
0.3
1
0.1
pN3
10
3.3
19
1.0
pN3a
10
3.3
19
1.0
pN3b
0
0.0
0
0.0
pN3c
0
0.0
0
0.0
pN1‑3
88
29.0
523
28.7
0.84
pNX
15
5.0
66
3.6
BC breast cancer, BVI blood vessel invasion, DCIS ductal carcinoma in situ, ER estrogen receptor, HER2 human epidermal growth factor receptor 2, IDC invasive ductal carcinoma, ILC invasive lobular carcinoma, Ki67 marker of proliferation Ki67, LVI lymphovascular invasion, pN pathological node stage, pNX unknown pathological node stage, PR progesterone receptor, pT pathological tumor stage, pTX unknown pathological tumor stage, SD standard deviation
a ILC versus IDC, χ2or Fisher’s exact test; unknown/undetermined values were excluded from the analysis
With respect to the tumors included, a concomitant DCIS component was found in 67 (22.1%) of ILC versus 915 (50.2%) of IDC (p < 0.001). Grade 2 was the most common tumor grade in both groups (218, 71.9% of ILC, 995, 54.6% of IDC, p < 0.001). Positive expression of ER was significantly more common among lobular tumors (n = 298, 98.3%) compared to IDC (n = 1529, 83.8%, p = 0.001). With respect to PR, there was no significant difference observed among the groups and HER2 was positive in only 15 (5.0%) of ILC versus 228 (12.5%) of invasive ductal tumors (p < 0.001). The proliferation rate (Ki67) was significantly different between both subgroups, we found a higher proportion of low and moderate Ki67 in ILC (n = 158, 52.1% and n = 122, 40.3%, respectively) in comparison with IDC (n = 670, 36.7% and n = 684, 37.5%, respectively) (p < 0.001). Regarding lymphovascular and blood vessel invasion (LVI, BVI), there was no significant difference between the histological subgroups.
In contrast, the pT and pN distribution differed significantly between ILC and IDC (both p < 0.001). The pT1 stage was found in 170 (56.1%) of lobular cancers versus 1332 (73.0%) of IDC. Invasive lobular tumors were more often diagnosed at a higher pT stage (pT2‑4, n = 132, 43.6%) compared to invasive ductal cases (n = 489, 26.8%). The most common pN stage was pN0 in both groups (200, 66.0% of ILC, 1235, 67.7% of IDC). The proportion of a positive pN stage (pN1-3) did not differ significantly between invasive lobular and ductal tumors (88, 29.0% versus 523, 28.7%, respectively, p = 0.84).
An axillary lymph node dissection was performed in 94 (31.0%) of invasive lobular versus 509 (27.9%) of invasive ductal carcinomas (p = 0.18). The mean total number of lymph nodes removed was 5.2 (SD: 5.6) in lobular versus 4.8 (SD: 5.1) in ductal tumors (p = 0.79) (Table 2).
Table 2
Axillary management: axillary lymph node dissection and total number of lymph nodes removed
 
Tumorstotal (n = 2127)
 
 
ILC (n = 303)
IDC (n = 1824)
 
 
n
%
n
%
p‑value a
Axillary lymph node dissection
Yes
94
31.0
509
27.9
0.18
No
201
66.3
1306
71.6
Unknown
8
2.6
9
0.5
Total number of lymph nodes removed
Evaluable tumors
275
90.8
1723
94.5
Total number of lymph nodes removed
1427
8296
Mean (SD)
5.2 (5.6)
4.8 (5.1)
0.79
IDC invasive ductal carcinoma, ILC invasive lobular carcinoma, SD standard deviation
a ILC versus IDC, χ2 or Fisher’s exact test; unknown/undetermined values were excluded from the analysis
In a univariate analysis of clinical pathological factors associated with ILC versus IDC, age at diagnosis, menopausal status, concomitant DCIS component, tumor grade, ER, HER2, Ki67, and pT and pN stages were found to be independent parameters; however, when these features were put into a multivariate regression model and adjusted for age, the following parameters were observed significantly more frequently in ILC compared with IDC: pN2 and pN3 (OR: 1.93; 95% CI: 1.19–3.14; p = 0.008; OR: 3.22; 95% CI: 1.47–7.03; p = 0.003, respectively), tumor grades 2 and 3 (OR: 2.99; 95% CI: 1.99–4.48; p < 0.001; OR: 1.63; 95% CI: 1.01–2.62; p = 0.045, respectively), positive ER (OR: 5.07; 95% CI: 1.85–13.88; p = 0.002), and pT2 and pT3 (OR: 1.72; 95% CI: 1.31–2.26; p < 0.001; OR: 6.31; 95% CI: 3.75–10.60; p < 0.001, respectively). In contrast, concomitant DCIS (OR: 0.29; 95% CI: 0.21–0.38; p < 0.001), HER2-positivity (OR: 0.36; 95% CI: 0.21–0.61; p < 0.001), and moderate or high Ki67 (OR: 0.76; 95% CI: 0.58–0.98; p = 0.034; OR: 0.31; 95% CI: 0.19–0.52; p < 0.001, respectively) were found less frequently in ILC (Table 3).
Table 3
Logistic regression analysis of ILC versus IDC: univariate and multivariate analysis
Characteristic
 
Univariate LR
p-value
Multivariate LR a
p-value
  
OR (95% CI)
 
OR (95% CI)
 
 
ILC vs. IDC
    
Age at diagnosis
(years)
1.01 per year (1.00–1.02)
0.011
20–39
1.0
40–59
1.61 (0.57–4.57)
0.373
60–79
1.97 (0.70–5.56)
0.200
80–99
2.05 (0.69–6.09)
0.194
Menopausal status
Premenopausal
1.0
Postmenopausal
1.46 (1.05–2.02)
0.024
1.11 (0.70–1.76)
0.654
Bilateral BC
No
1.0
Yes
1.41 (0.57–3.44)
0.457
1.32 (0.54–3.24)
0.550
DCIS component
No
1.0
Yes
0.28 (0.21–0.37)
<0.001
0.29 (0.21–0.38)
<0.001
Tumor grade
1
1.0
2
3.01 (2.01–4.52)
<0.001
2.99 (1.99–4.48)
<0.001
3
1.68 (1.04–2.70)
0.033
1.63 (1.01–2.62)
0.045
ER
Negative
1.0
Positive
4.87 (1.78–13.33)
0.002
5.07 (1.85–13.88)
0.002
PR
Negative
1.0
Positive
0.88 (0.62–1.23)
0.449
0.92 (0.65–1.29)
0.616
HER2
Negative
1.0
Positive
0.37 (0.21–0.63)
<0.001
0.36 (0.21–0.61)
<0.001
Ki67
Low
1.0
Moderate
0.76 (0.58–0.98)
0.035
0.76 (0.58–0.98)
0.034
High
0.31 (0.19–0.52)
<0.001
0.31 (0.19–0.52)
<0.001
LVI
No
1.0
Yes
0.98 (0.72–1.34)
0.904
0.97 (0.71–1.33)
0.869
BVI
No
1.0
Yes
1.19 (0.50–2.88)
0.693
1.13 (0.47–2.73)
0.787
pT stage
pT1
1.0
pT2
1.76 (1.34–2.31)
<0.001
1.72 (1.31–2.26)
<0.001
pT3
6.49 (3.87–10.89)
<0.001
6.31 (3.75–10.60)
<0.001
pT4
2.18 (0.80–5.94)
0.129
1.96 (0.72–5.39)
0.190
pN stage
pN0
1.0
pN1
0.78 (0.56–1.07)
0.123
0.79 (0.57–1.09)
0.149
pN2
1.98 (1.22–3.20)
0.006
1.93 (1.19–3.14)
0.008
pN3
3.25 (1.49–7.09)
0.003
3.22 (1.47–7.03)
0.003
pN0
1.0
pN1‑3
1.04 (0.79–1.36)
0.782
1.05 (0.80–1.38)
0.730
BC breast cancer, BVI blood vessel invasion, CI confidence interval, DCIS ductal carcinoma in situ, ER estrogen receptor, HER2 human epidermal growth factor receptor 2, IDC invasive ductal carcinoma, ILC invasive lobular carcinoma, LR logistic regression, LVI lymphovascular invasion, OR odds ratio, pN pathological node stage, PR progesterone receptor, pT pathological tumor stage
a adjusted for age at diagnosis

Discussion

The aim of this study was to perform a comparison of the ALN status in ILC and IDC. In order to address this question, we retrospectively analyzed data of a national register, the Clinical Tumor Register (KTR) of the Austrian Association for Gynecological Oncology (AGO). A total of 2127 tumors were evaluated and compared in 2 groups (ILC n = 303, IDC n = 1824). In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (OR: 1.93; 95% CI: 1.19–3.14; p = 0.008; OR: 3.22; 95% CI: 1.47–7.03; p = 0.003, respectively). Furthermore, multivariate analysis identified tumor grades 2 and 3, positive ER, and pT2 and pT3 as other factors associated with ILC. In contrast, a concomitant DCIS component, HER2-positivity, and moderate or high Ki67 were found less frequently in ILC compared to IDC. Taken together, our data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.
In our study, mean age at diagnosis was significantly different (ILC: 65.0 years, IDC: 63.0 years, p = 0.01). Older age at diagnosis has been reported in several studies [6, 10, 11, 13, 17, 26, 31, 33]. Otherwise, age at diagnosis did not differ significantly between ILC and IDC [3436]. Compared to patients with IDC, patients with ILC were less frequently premenopausal in our analysis; however, there are reports about no difference regarding the menopausal status in the literature [17, 33].
Patients with ILC presented more frequently with grade 2 tumors in comparison with IDC patients. This has been reported previously in several studies [13, 17, 29, 31]. According to our findings, more frequent ER-positivity in ILC was observed in different studies comparing these tumors with IDC [7, 9, 10, 16, 17, 29, 36]. We found more HER2-negative tumors with ILC, and several similar reports exist in the literature [1, 10, 12, 13, 37]. Our findings show a slow or moderate proliferation rate (Ki67) more frequently in lobular tumors. Other studies revealed that ILC was more often slowly proliferative [10, 12, 37]. In our analysis, there were no significant differences found according to bilateral BC, PR, lymphovascular and blood vessel invasion.
As in our study, ILC was associated with a larger tumor size in several trials [68, 10, 12, 13, 17, 29, 31, 38]; however, some studies found no difference in tumor size between ILC and IDC [16, 26, 35, 36].
In the descriptive analysis, we found a significantly different pN distribution between ILC and IDC. The multivariate analysis identified pN2 and pN3 as associated with ILC; however, published data on the ALN status in ILC compared with IDC are controversial [8, 10, 2631]. Table 4 represents an overview of published data on the nodal status in association with the histological subtype.
Table 4
Published data on the ALN involvement in ILC compared with IDC
No difference in ALN involvement between ILC and IDC
Association between ILC and higher incidence of positive ALN involvement
Association between ILC and lower incidence of positive ALN involvement
Silverstein et al. (1994) [27]
Li et al. (2005) [38]
Sastre-Garau et al. (1996) [9]
Casolo et al. (1997) [39]
Wasif et al. (2010) [7]
Vandorpe et al. (2011) [31]
Mersin et al. (2003) [26]
Fernandez et al. (2011) [8]
Gao et al. (2020) [30]
Arpino et al. (2004) [10]
Chen et al. (2017) [13]
Classe et al. (2004) [40]
Corona et al. (2020) [28]
Pestalozzi et al. (2008) [17]
Danzinger et al. (2021) [29]
Rakha et al. (2008) [11]
Lee at al. (2010) [36]
Jung et al. (2010) [12]
Biglia et al. (2013) [16]
Zengel et al. (2015) [33]
ALN axillary lymph node, IDC invasive ductal carcinoma, ILC invasive lobular carcinoma
Most studies showed that the ALN involvement did not differ between these histopathological groups [1012, 16, 17, 26, 27, 33, 36, 39, 40]. Arpino et al. [10] compared 4140 patients with ILC with 45,169 patients with IDC; there was no difference in the frequency of ALN involvement. Furthermore, nodal status did not differ between ILC and IDC in an analysis of 13,220 patients [17]; however, several studies found an association between ILC and a higher incidence of ALN positivity [7, 8, 13, 28, 29, 38]. Wasif et al. [7] demonstrated that ILC was more likely to be lymph node positive, when compared to IDC (36.8% versus 34.4%; p < 0.001). Evaluation of the Surveillance, Epidemiology and End Results Program (SEER) database showed a correlation between the ILC group and greater counts of positive lymph nodes [13]. In contrast, there are studies showing less frequent ALN involvement in ILC [9, 30, 31]. In a multivariate analysis, Vandorpe et al. [31] identified ILC as less likely to have ALN involvement (adjusted OR: 0.66; 95% CI: 0.53–0.82; p < 0.001). The authors retrospectively investigated 4292 tumors (ILC versus non-ILC). In contrast to our study, tumors with mixed ductal and lobular phenotypes were included. In conclusion, the lobular histology has been identified as an independent predictor of ALN involvement.
Limitations of this study are a moderate sample size and the retrospective design. Nevertheless, our results were similar to previously reported findings. In our analysis, we did not differentiate between the histological subtypes of ILC (e.g. classical, solid, alveolar); however, it is important to note that the patient collective of this investigation is quite homogeneous due to the inclusion and exclusion criteria: all patients underwent primary surgery, no patients with recurrent disease, or metastasis at the time of diagnosis.
In summary, this study was based on an Austrian cancer register. Our findings demonstrate an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC. Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pT2 and pT3. In contrast, DCIS component, HER2+, and moderate or high Ki67 were found less frequently in ILC.
In the future, meta-analyses and pooling of data are required to make progress in research of ILC as a distinct histologic type of BC.

Conclusion

The findings support an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.

Funding

There is no funding of the study.

Declarations

Conflict of interest

S. Danzinger, K. Pöckl, G. Kronawetter, C. Pfeifer, S. Behrendt, P. Gscheidlinger, L. Harrasser, H. Mühlböck, W. Dirschlmayer, C. Schauer, R. Reitsamer, H. Uher, K. Schönau, I. Delmarko and C.F. Singer declare that they have no competing interests.

Ethical standards

The study was approved by the ethics committee of the Medical University of Vienna. All procedures performed in our study were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. According to the ethics committee of the Medical University of Vienna, written informed consent was not required owing to the retrospective design of the study.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Unsere Produktempfehlungen

Abo für kostenpflichtige Inhalte

Literatur
1.
Zurück zum Zitat Mamtani A, King TA. Lobular breast cancer: different disease, different algorithms? Surg Oncol Clin N Am. 2018;27:81–94.CrossRefPubMed Mamtani A, King TA. Lobular breast cancer: different disease, different algorithms? Surg Oncol Clin N Am. 2018;27:81–94.CrossRefPubMed
2.
Zurück zum Zitat Thomas M, Kelly ED, Abraham J, Kruse M. Invasive lobular breast cancer: a review of pathogenesis, diagnosis, management, and future directions of early stage disease. Semin Oncol. 2019;46:121–32.CrossRefPubMed Thomas M, Kelly ED, Abraham J, Kruse M. Invasive lobular breast cancer: a review of pathogenesis, diagnosis, management, and future directions of early stage disease. Semin Oncol. 2019;46:121–32.CrossRefPubMed
3.
Zurück zum Zitat McCart Reed AE, Kutasovic JR, Lakhani SR, Simpson PT. Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics. Breast Cancer Res. 2015;17:12.CrossRefPubMed McCart Reed AE, Kutasovic JR, Lakhani SR, Simpson PT. Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics. Breast Cancer Res. 2015;17:12.CrossRefPubMed
4.
Zurück zum Zitat Dabbs DJ, Schnitt SJ, Geyer FC, Weigelt B, Baehner FL, Decker T, et al. Lobular neoplasia of the breast revisited with emphasis on the role of E‑cadherin immunohistochemistry. Am J Surg Pathol. 2013;37:e1–11.CrossRefPubMed Dabbs DJ, Schnitt SJ, Geyer FC, Weigelt B, Baehner FL, Decker T, et al. Lobular neoplasia of the breast revisited with emphasis on the role of E‑cadherin immunohistochemistry. Am J Surg Pathol. 2013;37:e1–11.CrossRefPubMed
5.
Zurück zum Zitat Wilson N, Ironside A, Diana A, Oikonomidou O. Lobular breast cancer: a review. Front Oncol. 2020;10:591399.CrossRefPubMed Wilson N, Ironside A, Diana A, Oikonomidou O. Lobular breast cancer: a review. Front Oncol. 2020;10:591399.CrossRefPubMed
6.
Zurück zum Zitat Williams LA, Hoadley KA, Nichols HB, Geradts J, Perou CM, Love MI, et al. Differences in race, molecular and tumor characteristics among women diagnosed with invasive ductal and lobular breast carcinomas. Cancer Causes Control. 2019;30:31–9.CrossRefPubMedPubMedCentral Williams LA, Hoadley KA, Nichols HB, Geradts J, Perou CM, Love MI, et al. Differences in race, molecular and tumor characteristics among women diagnosed with invasive ductal and lobular breast carcinomas. Cancer Causes Control. 2019;30:31–9.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: a stage-matched comparison of outcomes. Ann Surg Oncol. 2010;17:1862–9.CrossRefPubMed Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: a stage-matched comparison of outcomes. Ann Surg Oncol. 2010;17:1862–9.CrossRefPubMed
8.
Zurück zum Zitat Fernandez B, Paish EC, Green AR, Lee AH, Macmillan RD, Ellis IO, et al. Lymph-node metastases in invasive lobular carcinoma are different from those in ductal carcinoma of the breast. J Clin Pathol. 2011;64:995–1000.CrossRefPubMed Fernandez B, Paish EC, Green AR, Lee AH, Macmillan RD, Ellis IO, et al. Lymph-node metastases in invasive lobular carcinoma are different from those in ductal carcinoma of the breast. J Clin Pathol. 2011;64:995–1000.CrossRefPubMed
9.
Zurück zum Zitat Sastre-Garau X, Jouve M, Asselain B, Vincent-Salomon A, Beuzeboc P, Dorval T, et al. Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer. 1996;77:113–20.CrossRefPubMed Sastre-Garau X, Jouve M, Asselain B, Vincent-Salomon A, Beuzeboc P, Dorval T, et al. Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer. 1996;77:113–20.CrossRefPubMed
10.
Zurück zum Zitat Arpino G, Bardou VJ, Clark GM, Elledge RM. Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res. 2004;6:R149–56.CrossRefPubMedPubMedCentral Arpino G, Bardou VJ, Clark GM, Elledge RM. Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res. 2004;6:R149–56.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Rakha EA, El-Sayed ME, Powe DG, Green AR, Habashy H, Grainge MJ, et al. Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer. 2008;44:73–83.CrossRefPubMed Rakha EA, El-Sayed ME, Powe DG, Green AR, Habashy H, Grainge MJ, et al. Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer. 2008;44:73–83.CrossRefPubMed
12.
Zurück zum Zitat Jung SY, Jeong J, Shin SH, Kwon Y, Kim EA, Ko KL, et al. The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study. BMC Cancer. 2010;10:664.CrossRefPubMedPubMedCentral Jung SY, Jeong J, Shin SH, Kwon Y, Kim EA, Ko KL, et al. The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study. BMC Cancer. 2010;10:664.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Chen Z, Yang J, Li S, Lv M, Shen Y, Wang B, et al. Invasive lobular carcinoma of the breast: a special histological type compared with invasive ductal carcinoma. PLoS ONE. 2017;12:e182397.CrossRefPubMedPubMedCentral Chen Z, Yang J, Li S, Lv M, Shen Y, Wang B, et al. Invasive lobular carcinoma of the breast: a special histological type compared with invasive ductal carcinoma. PLoS ONE. 2017;12:e182397.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Pramod N, Nigam A, Basree M, Mawalkar R, Mehra S, Shinde N, et al. Comprehensive review of molecular mechanisms and clinical features of invasive lobular cancer. Oncologist. 2021;26:e943–e53.CrossRefPubMedPubMedCentral Pramod N, Nigam A, Basree M, Mawalkar R, Mehra S, Shinde N, et al. Comprehensive review of molecular mechanisms and clinical features of invasive lobular cancer. Oncologist. 2021;26:e943–e53.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Luveta J, Parks RM, Heery DM, Cheung KL, Johnston SJ. Invasive lobular breast cancer as a distinct disease: implications for therapeutic strategy. Oncol Ther. 2020;8:1–11.CrossRefPubMed Luveta J, Parks RM, Heery DM, Cheung KL, Johnston SJ. Invasive lobular breast cancer as a distinct disease: implications for therapeutic strategy. Oncol Ther. 2020;8:1–11.CrossRefPubMed
16.
Zurück zum Zitat Biglia N, Maggiorotto F, Liberale V, Bounous VE, Sgro LG, Pecchio S, et al. Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Eur J Surg Oncol. 2013;39:455–60.CrossRefPubMed Biglia N, Maggiorotto F, Liberale V, Bounous VE, Sgro LG, Pecchio S, et al. Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Eur J Surg Oncol. 2013;39:455–60.CrossRefPubMed
17.
Zurück zum Zitat Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, et al. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol. 2008;26:3006–14.CrossRefPubMed Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, et al. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol. 2008;26:3006–14.CrossRefPubMed
18.
Zurück zum Zitat Ferlicot S, Vincent-Salomon A, Medioni J, Genin P, Rosty C, Sigal-Zafrani B, et al. Wide metastatic spreading in infiltrating lobular carcinoma of the breast. Eur J Cancer. 2004;40:336–41.CrossRefPubMed Ferlicot S, Vincent-Salomon A, Medioni J, Genin P, Rosty C, Sigal-Zafrani B, et al. Wide metastatic spreading in infiltrating lobular carcinoma of the breast. Eur J Cancer. 2004;40:336–41.CrossRefPubMed
19.
Zurück zum Zitat Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983;52:1551–7.CrossRefPubMed Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983;52:1551–7.CrossRefPubMed
20.
Zurück zum Zitat Russo J, Frederick J, Ownby HE, Fine G, Hussain M, Krickstein HI, et al. Predictors of recurrence and survival of patients with breast cancer. Am J Clin Pathol. 1987;88:123–31.CrossRefPubMed Russo J, Frederick J, Ownby HE, Fine G, Hussain M, Krickstein HI, et al. Predictors of recurrence and survival of patients with breast cancer. Am J Clin Pathol. 1987;88:123–31.CrossRefPubMed
21.
Zurück zum Zitat Fisher ER, Anderson S, Redmond C, Fisher B. Pathologic findings from the national surgical adjuvant breast project protocol B‑06. 10-year pathologic and clinical prognostic discriminants. Cancer. 1993;71:2507–14.CrossRefPubMed Fisher ER, Anderson S, Redmond C, Fisher B. Pathologic findings from the national surgical adjuvant breast project protocol B‑06. 10-year pathologic and clinical prognostic discriminants. Cancer. 1993;71:2507–14.CrossRefPubMed
22.
Zurück zum Zitat Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–78.CrossRefPubMed Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–78.CrossRefPubMed
23.
Zurück zum Zitat Vinh-Hung V, Joseph SA, Coutty N, Ly BH, Vlastos G, Nguyen NP. Age and axillary lymph node ratio in postmenopausal women with T1–T2 node positive breast cancer. Oncologist. 2010;15:1050–62.CrossRefPubMedPubMedCentral Vinh-Hung V, Joseph SA, Coutty N, Ly BH, Vlastos G, Nguyen NP. Age and axillary lymph node ratio in postmenopausal women with T1–T2 node positive breast cancer. Oncologist. 2010;15:1050–62.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Schiffman SC, McMasters KM, Scoggins CR, Martin RC, Chagpar AB. Lymph node ratio: a proposed refinement of current axillary staging in breast cancer patients. J Am Coll Surg. 2011;213:45–52. discussion –3.CrossRefPubMed Schiffman SC, McMasters KM, Scoggins CR, Martin RC, Chagpar AB. Lymph node ratio: a proposed refinement of current axillary staging in breast cancer patients. J Am Coll Surg. 2011;213:45–52. discussion –3.CrossRefPubMed
25.
Zurück zum Zitat Singh D, Mandal A. The prognostic value of lymph node ratio in survival of non-metastatic breast carcinoma patients. Breast Cancer Res Treat. 2020;184:839–48.CrossRefPubMed Singh D, Mandal A. The prognostic value of lymph node ratio in survival of non-metastatic breast carcinoma patients. Breast Cancer Res Treat. 2020;184:839–48.CrossRefPubMed
26.
Zurück zum Zitat Mersin H, Yildirim E, Gulben K, Berberoglu U. Is invasive lobular carcinoma different from invasive ductal carcinoma? Eur J Surg Oncol. 2003;29:390–5.CrossRefPubMed Mersin H, Yildirim E, Gulben K, Berberoglu U. Is invasive lobular carcinoma different from invasive ductal carcinoma? Eur J Surg Oncol. 2003;29:390–5.CrossRefPubMed
27.
Zurück zum Zitat Silverstein MJ, Lewinsky BS, Waisman JR, Gierson ED, Colburn WJ, Senofsky GM, et al. Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma? Cancer. 1994;73:1673–7.CrossRefPubMed Silverstein MJ, Lewinsky BS, Waisman JR, Gierson ED, Colburn WJ, Senofsky GM, et al. Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma? Cancer. 1994;73:1673–7.CrossRefPubMed
28.
Zurück zum Zitat Corona SP, Bortul M, Scomersi S, Bigal C, Bottin C, Zanconati F, et al. Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers. Breast Cancer Res Treat. 2020;180:735–45.CrossRefPubMed Corona SP, Bortul M, Scomersi S, Bigal C, Bottin C, Zanconati F, et al. Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers. Breast Cancer Res Treat. 2020;180:735–45.CrossRefPubMed
29.
Zurück zum Zitat Danzinger S, Hielscher N, Izso M, Metzler J, Trinkl C, Pfeifer C, et al. Invasive lobular carcinoma: clinicopathological features and subtypes. J Int Med Res. 2021;49:3000605211017039.CrossRefPubMed Danzinger S, Hielscher N, Izso M, Metzler J, Trinkl C, Pfeifer C, et al. Invasive lobular carcinoma: clinicopathological features and subtypes. J Int Med Res. 2021;49:3000605211017039.CrossRefPubMed
30.
Zurück zum Zitat Gao W, Zeng Y, Fei X, Chen X, Shen K. Axillary lymph node and non-sentinel lymph node metastasis among the ACOSOG Z0011 eligible breast cancer patients with invasive ductal, invasive lobular, or other histological special types: a multi-institutional retrospective analysis. Breast Cancer Res Treat. 2020;184:193–202.CrossRefPubMed Gao W, Zeng Y, Fei X, Chen X, Shen K. Axillary lymph node and non-sentinel lymph node metastasis among the ACOSOG Z0011 eligible breast cancer patients with invasive ductal, invasive lobular, or other histological special types: a multi-institutional retrospective analysis. Breast Cancer Res Treat. 2020;184:193–202.CrossRefPubMed
31.
Zurück zum Zitat Vandorpe T, Smeets A, Van Calster B, Van Hoorde K, Leunen K, Amant F, et al. Lobular and non-lobular breast cancers differ regarding axillary lymph node metastasis: a cross-sectional study on 4,292 consecutive patients. Breast Cancer Res Treat. 2011;128:429–35.CrossRefPubMed Vandorpe T, Smeets A, Van Calster B, Van Hoorde K, Leunen K, Amant F, et al. Lobular and non-lobular breast cancers differ regarding axillary lymph node metastasis: a cross-sectional study on 4,292 consecutive patients. Breast Cancer Res Treat. 2011;128:429–35.CrossRefPubMed
32.
Zurück zum Zitat R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2022. www.r-project.org. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2022. www.​r-project.​org.
33.
Zurück zum Zitat Zengel B, Yararbas U, Duran A, Uslu A, Eliyatkin N, Demirkiran MA, et al. Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast. Breast Cancer. 2015;22:374–81.CrossRefPubMed Zengel B, Yararbas U, Duran A, Uslu A, Eliyatkin N, Demirkiran MA, et al. Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast. Breast Cancer. 2015;22:374–81.CrossRefPubMed
34.
Zurück zum Zitat Yeatman TJ, Cantor AB, Smith TJ, Smith SK, Reintgen DS, Miller MS, et al. Tumor biology of infiltrating lobular carcinoma. Implications for management. Ann Surg. 1995;222:549–59. discussion 59–61.CrossRefPubMedPubMedCentral Yeatman TJ, Cantor AB, Smith TJ, Smith SK, Reintgen DS, Miller MS, et al. Tumor biology of infiltrating lobular carcinoma. Implications for management. Ann Surg. 1995;222:549–59. discussion 59–61.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Winchester DJ, Chang HR, Graves TA, Menck HR, Bland KI, Winchester DP. A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes. J Am Coll Surg. 1998;186:416–22.CrossRefPubMed Winchester DJ, Chang HR, Graves TA, Menck HR, Bland KI, Winchester DP. A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes. J Am Coll Surg. 1998;186:416–22.CrossRefPubMed
36.
Zurück zum Zitat Lee JH, Park S, Park HS, Park BW. Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study. World J Surg Oncol. 2010;8:34.CrossRefPubMedPubMedCentral Lee JH, Park S, Park HS, Park BW. Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study. World J Surg Oncol. 2010;8:34.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Korhonen T, Huhtala H, Holli K. A comparison of the biological and clinical features of invasive lobular and ductal carcinomas of the breast. Breast Cancer Res Treat. 2004;85:23–9.CrossRefPubMed Korhonen T, Huhtala H, Holli K. A comparison of the biological and clinical features of invasive lobular and ductal carcinomas of the breast. Breast Cancer Res Treat. 2004;85:23–9.CrossRefPubMed
38.
39.
Zurück zum Zitat Casolo P, Raspadori A, Drei B, Amuso D, Mosca D, Amorotti C, et al. Natural history of breast cancer: lobular carcinoma versus ductal carcinoma in our experience. Ann Ital Chir. 1997;68:43–7. discussion 8.PubMed Casolo P, Raspadori A, Drei B, Amuso D, Mosca D, Amorotti C, et al. Natural history of breast cancer: lobular carcinoma versus ductal carcinoma in our experience. Ann Ital Chir. 1997;68:43–7. discussion 8.PubMed
40.
Zurück zum Zitat Classe JM, Loussouarn D, Campion L, Fiche M, Curtet C, Dravet F, et al. Validation of axillary sentinel lymph node detection in the staging of early lobular invasive breast carcinoma: a prospective study. Cancer. 2004;100:935–41.CrossRefPubMed Classe JM, Loussouarn D, Campion L, Fiche M, Curtet C, Dravet F, et al. Validation of axillary sentinel lymph node detection in the staging of early lobular invasive breast carcinoma: a prospective study. Cancer. 2004;100:935–41.CrossRefPubMed
Metadaten
Titel
Axillary lymph node status and invasive lobular breast cancer
Analysis of the Clinical Tumor Register of the AGO Austria
verfasst von
Sabine Danzinger, MD
Karin Pöckl
Gerit Kronawetter
Christian Pfeifer
Sandra Behrendt
Patricia Gscheidlinger
Lois Harrasser
Helmut Mühlböck
Walter Dirschlmayer
Christian Schauer
Roland Reitsamer
Heidemarie Uher
Kristina Schönau
Irmgard Delmarko
Christian F. Singer
Publikationsdatum
03.04.2023
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 17-18/2023
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-023-02162-y

Weitere Artikel der Ausgabe 17-18/2023

Wiener klinische Wochenschrift 17-18/2023 Zur Ausgabe