Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer

Figures & data

Table 1 Clinical and pathologic characteristics of the patients

Characteristic	Number	%
Number of patients	28	100.0
Age (years)
<50	18	64.3
≥50	10	35.7
Clinical (T) stage
T2	15	53.6
T3	6	21.4
T4d	7	25.0
LVSI
Negative	12	42.9
Positive	16	27.1
Type of lesion
Unifocal	9	32.1
Multifocal	10	45.8
Multifocal and multicentric	9	32.1
Grade
1	5	17.9
2	9	32.1
3	14	50.0
Tumor size before CTX
20–30 mm	13	46.4
31–50 mm	4	14.4
>50 mm	11	39.2
Pathological (ypT) stage
ypT0	2	7.1
ypT1	10	35.7
ypT2	11	39.3
ypT3	1	3.6
ypT4	4	14.3
Tumor histology
Ductal	12	42.9
Lobular	10	35.7
Mixed	3	10.7
Other	3	10.7
ER status
Negative	7	25.0
Positive	21	75.0
PgR status
Negative	8	28.6
Positive	20	71.4
HER2 status
Negative	23	82.1
Positive	5	17.9
Ki-67
<15%	11	39.3
≥15%	17	60.7
<50%	21	75.0
≥50%	7	25.0

Abbreviations: CTX, chemotherapy; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; LVSI, lymphovascular space invasion; PgR, progesterone receptor.

Figure 1 Immunostaining for TOP2A in preoperative breast cancer core biopsies.

Note: Staining was (A) positive (≥30% positivity) (×200) or (B) negative (<30% positivity) (×200).
Abbreviation: TOP2A, topoisomerase II alpha.

Figure 2 Immunostaining for TLE3 in preoperative breast cancer core biopsies.

Note: Staining was (A) positive (≥1% positivity) (×200) or (B) negative (null positivity) (×200).
Abbreviation: TLE3, transducin-like enhancer of split 3.

Table 2 Tumor diameter before and after neoadjuvant chemotherapy treatment

Tumor size (mm)	Before CTX		After CTX
	Number	%	Number	%
0–19	–	–	10	35.6
20–30	13	46.4	10	35.6
31–50	4	14.4	5	18.0
>50	11	39.2	3	10.8

Abbreviation: CTX, chemotherapy.

Table 3 Distribution by size reduction (%) after chemotherapy treatment

Size reduction (%)	Number	%
0–19	3	10.7
20–49	13	46.4
50–69	6	21.4
70–99	4	14.3
100	2	7.2

Table 4 Probability to obtain a tumor size reduction ≥70% after neoadjuvant chemotherapy according to clinical–pathological and IHC features (logistic regression analysis)

Characteristic	Size reduction ≥70%
	HR	95% CI	P-value
Age (years)
<50	1
≥50	17.0	1.59–181.36	0.01
ER (%)
<70	1
≥70	0.14	0.02–1.05	0.05
PgR (%)
<10	1
≥10	0.09	0.009–0.95	0.04
TLE3
Positive	1
Negative	12.5	0.81–166.66	0.07
TOP2A
Negative	1
Positive	9.0	0.88–91.25	0.06
Ki-67
<50%	1
≥50%	4.50	0.65–31.08	0.12
HER2
Negative	1
Positive	0.90	0.08–9.97	0.93
Triple-negative
No	1
Yes	3.16	0.39–25.57	0.27
Grade
1–2	1
3	2.40	0.36–15.94	0.36
Pathological (ypT) stage
T2	1
T3–T4	3.16	0.39–25.57	0.27
LVSI
Negative	1
Positive	0.28	0.04–1.92	0.19
Type of lesion
Not multicentric	1
Multicentric	3.21	0.43–23.78	0.25
Tumor histology
Ductal	1
Others	0.28	0.04–1.92	0.19

Abbreviations: CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; LVSI, lymphovascular space invasion; PgR, progesterone receptor; TLE3, transducin-like enhancer of split 3; TOP2A, topoisomerase II alpha.

Figure 3 Distribution of good responders according toTOP2A status.

Abbreviation: TOP2A, topoisomerase II alpha.

Figure 4 Disease-free survival according to TOP2A positivity.

Abbreviation: TOP2A, topoisomerase II alpha.

Figure 5 Distribution of good responders according to TLE3 status.

Abbreviation: TLE3, transducin-like enhancer of split 3.

Figure 6 Distribution of good responders according to concurrent TOP2A positivity and TLE3 negativity.

Abbreviations: TLE3, transducin-like enhancer of split 3; TOP2A, topoisomerase II alpha.

Figure 7 Disease-free survival estimates for patients with concurrent TOP2A-positive and TLE3-negative tumors, in comparison with all other patients.

Abbreviations: TLE3, transducin-like enhancer of split 3; TOP2A, topoisomerase II alpha.

Figure 8 Disease-free survival estimates for patients with response to neoadjuvant chemotherapy, resulting in comparison of ypT1–T2 stage patients with ypT3–T4 stage patients.