The study included 203 female patients. The mean age was 51.5±11.4 years (range: 26-78).82.8% of the patients were over 40 years of age and 54.7% were postmenopausal. ECOG performance score was 0 in 91.5%, 1 in 8%, and 2 in 0.5%.According to the initial core biopsy results, the clinical subtype was Luminal in 155 patients (76.4%), Her-2 enriched in 16 patients (7.9%) and triple negative in 32 patients (15.8%).The average follow-up period was 31.9 months. As a result, recurrence or metastasis developed in 40 patients (19.7%), and mortality occurred in 24 patients (11.8%).Clinical and pathological characteristics of the patients are shown in Table 1.
Table 1: Clinical and pathological characteristics of the patients
Parameter
|
Sub-group
|
N
|
%
|
Age
|
<40
|
35
|
17.2
|
≥40
|
168
|
82.8
|
Menopausal state
|
Premenopausal
|
92
|
45.3
|
Postmenopausal
|
111
|
54.7
|
cT
|
T1
|
28
|
13.8
|
T2
|
109
|
53.7
|
T3
|
39
|
19.2
|
T4
|
27
|
13.3
|
cN
|
N0
|
20
|
9.9
|
N1
|
109
|
53.7
|
N2
|
64
|
31.5
|
N3
|
10
|
4.9
|
ypT
|
T1
|
138
|
69.3
|
T2
|
46
|
23.1
|
T3
|
11
|
5.5
|
T4
|
4
|
2.0
|
ypN
|
N0
|
71
|
35.7
|
N1
|
72
|
36.2
|
N2
|
48
|
24.1
|
N3
|
8
|
4.0
|
Pretreatment Ki-67
|
high (≥ 15%)
|
191
|
94.1
|
low (< 15%)
|
12
|
5.9
|
Posttreatment Ki-67
|
high (≥ 15%)
|
103
|
57.5
|
low (< 15%)
|
76
|
42.5
|
Focality
|
Unilocal
|
136
|
67.3
|
Multifocal
|
32
|
15.8
|
Multicentric
|
11
|
5.4
|
Multifocal +multicentric
|
23
|
11.4
|
Histology
|
NOS
|
69
|
34.0
|
ILC
|
13
|
6.4
|
IDC
|
96
|
47.3
|
Other
|
25
|
12.3
|
Grade
|
1
|
4
|
2.0
|
2
|
120
|
60.3
|
3
|
75
|
37.7
|
Surgery type
|
BCS
|
81
|
39.9
|
MRM
|
78
|
38.4
|
Simple Mastectomy
|
37
|
18.2
|
Bilateral MRM
|
3
|
1.5
|
Bilateral Symple Mastectomy
|
4
|
2.0
|
T;Tumour,N;Node,C;Clinic,ILC;Invasive lobular carcinoma,IDC;Invasive ductal carcinoma, NOS;Not other specified BCS;Breast conserving surgery,MRM;Modified radical mastectomy,Yp;Staging following neoadjuvant therapy
Changes in receptor and pathological features evaluated in core biopsy and surgical specimens are shown in Table 2. Tumour grade and Ki-67 proliferation index were statistically significantly lower in surgical specimens after NACT.
Table -2 :Pre-operative and post-operative changes in pathological features
|
|
Pre
|
Post
|
|
Features
|
|
n
|
%
|
n
|
%
|
P*
|
Grade
|
1
|
4
|
2.0
|
118
|
58.1
|
0.003
|
2
|
120
|
60.3
|
19
|
9.4
|
|
3
|
75
|
37.7
|
34
|
16.7
|
|
ER positivity
|
0
|
49
|
24.1
|
32
|
15.8
|
0.600
|
1
|
10
|
4.9
|
118
|
58.1
|
|
2
|
19
|
9.4
|
19
|
9.4
|
|
3
|
125
|
61.6
|
34
|
16.7
|
|
PR positivity
|
0
|
77
|
37.9
|
32
|
15.8
|
0.091
|
1
|
14
|
6.9
|
118
|
58.1
|
|
2
|
27
|
13.3
|
19
|
9.4
|
|
3
|
85
|
41.9
|
34
|
16.7
|
|
HER-2
|
0
|
118
|
58,1
|
32
|
15,8
|
0.104
|
1
|
19
|
9.4
|
118
|
58.1
|
|
2
|
34
|
16.7
|
19
|
9.4
|
|
3
|
32
|
15.8
|
34
|
16.7
|
|
Ki-67(mean±SD)
|
39.6±21.4 (3-90)
|
24.7±22.7 (1-95)
|
<0.001
|
*McNemar-Bowker Test, ER;oestrogen,PR;progesterone,HER-2; Human epidermal growth factor 2; The percentage of tumor cells expressing the ER or PR receptor in the nucleus of the cells is recorded along with assessment of receptor staining strength (negative, weak, moderate, strong). Staining strength is scored from 0 to 3+.
Among 203 patients, 127 (62.6%) had no receptor change. In 58 patients (28.6%), only one receptor was changed. 14 patients (6.9%) had changes in 2 receptors and 4 patients (2%) had changes in all three receptors.
ER status changed in a total of 24 patients (11.8%). Of these, 10 patients changed from positive to negative, and 14 patients changed from negative to positive. PR status changed in 50 patients (24.6%). 29 patients changed from positive to negative, and 21 patients changed from negative to positive. HER-2 status changed in 26 patients (12.5%). Of these, 19 patients changed from positive to negative, and 7 patients changed from negative to positive.
While the 5-year survival rate is 87.5% in patients whose ER status is positive but does not change, it is 66.7% in patients whose ER status is positive but changes to negative, 84.4% in patients whose ER status is negative but changes to positive, and 66.7% in patients whose ER status is negative but changes to positive. It was determined as 57.4% in patients with negative ER status and unchanged (p=0.029).Survival rates of the ER negative group who remained negative after NACT were statistically significantly lower than those who remained positive (p=0.002). No significant difference was found in patients with ER change compared to those without (Figure 1).
3-year Disease Free Survival (DFS) was 75.6% in those whose ER status was positive and did not change, 56.8% in those whose ER status was negative and did not change, 66.7% in those whose ER status was positive and turned negative, and 64.9% in those whose ER status was negative and turned positive, and there was no statistically significant difference (p=0.387).
According to the PR status, the 5-year survival rate was 82.6% in those who were positive and did not change, 68% in those who were negative and did not change, 100% in those who changed from positive to negative, and 80.2% in those who changed from negative to positive (p=0.042). Survival rates of the groups with PR change from negative to negative and negative to positive were statistically significantly lower than those with positive to negative ( p=0.011 p=0.049) (Figure 2).
5-year DFS rates were 51.8% in PR positive patients who did not change, 47.4% in negative patients who did not change, 73.8% in positive patients who turned negative, and 51.8% in negative patients who turned positive and there was no statistical significance (p=0.696).
5-year survival was 95.2% in HER-2 positive and unchanged, 77.4% in HER-2 positive and changed to negative, 83% in HER-2 negative and changed to positive, and 78.5% in HER-2 negative and unchanged. There was no statistically significant difference in survival rates in HER-2 change groups (p=0.915) (Figure 3). 5-year DFS was 40.1% in HER-2 positive patients who did not change, 78.6% in those who turned positive to negative, 62.4% in those who turned negative to positive, and 54.4% in those who turned negative to positive and did not change, and was not statistically significant (p=0.816). Intergroup survival rate analyzes according to ER, PR and HER-2 status are presented in table 3.
Table 3. Intergroup survival rate analyzes according to ER, PR and HER-2 status
ERstatus
|
|
Positive to negative
|
Positive to positive
|
Negative to positive
|
|
p
|
p
|
p
|
Positive to positive
|
0.810
|
|
|
Negative to positive
|
0.756
|
0.399
|
|
Negative to negative
|
0.254
|
0.002
|
0.694
|
PR Status
|
|
Positive to negative
|
Positive to positive
|
Negative to positive
|
|
p
|
p
|
p
|
Positive to positive
|
0.089
|
|
|
Negative to positive
|
0.049
|
0.591
|
|
Negative to negative
|
0.011
|
0.069
|
0.603
|
HER-2 Status
|
|
Positive to negative
|
Positive to positive
|
Negative to positive
|
|
p
|
p
|
p
|
Positive to positive
|
0.641
|
|
|
Negative to positive
|
0.874
|
0.690
|
|
Negative to negative
|
0.837
|
0.452
|
0.777
|
ER;oestrogen,PR;progesterone,HER-2; Human epidermal growth factor 2