Introduction
Methods
Study population and tumor bank
Aromatase immunohistochemistry
Statistics
Results
Aromatase expression and correlation with baseline pathological and clinical variables
Characteristics | Aromatase protein expression [n (%)]b
| |||
---|---|---|---|---|
Tumor epithelial aromatase | Stromal aromatase | |||
Negative | Positive | Negative | Positive | |
Treatment | ||||
Tamoxifen | 24 (53%) | 72 (49%) | 29 (54) | 63 (48) |
Letrozole | 21 (47%) | 75 (51%) | 25 (46) | 69 (52) |
P-value | 0.6102 | 0.4605 | ||
Age (year) | 66.8 | 67.6 | 67.6 | 67 |
P-valuec
| 0.6214 | 0.6969 | ||
Clinical tumor size (cm) | 5.7 | 4.8 | 5.5 | 4.7 |
P-valuec
| 0.0144 | 0.0398 | ||
Pre treatment grade | ||||
I | 4 (10%) | 16 (13%) | 4 (8%) | 16 (15%) |
II/III | 38 (90%) | 103 (87%) | 47 (92%) | 90 (85%) |
P-value | 0.5971 | 0.3064 | ||
Pathological tumor size | ||||
≤20 mm | 11 (27%) | 44 (32%) | 11 (27%) | 44 (32%) |
>20 mm | 30 (73%) | 95 (68%) | 30 (73%) | 95 (68%) |
P-value | 0.5567 | 0.5567 | ||
Pathological node status | ||||
Negative | 16 (41%) | 55 (43%) | 21 (47%) | 50 (43%) |
Positive | 23 (59%) | 72 (57%) | 24 (53%) | 65 (57%) |
P-value | 0.8017 | 0.7160 | ||
HER2 statusa
| ||||
Negative | 40 (91%) | 140 (95%) | 50 (93%) | 125 (95%) |
Positive | 4 (9%) | 7 (5%) | 4 (7%) | 6 (5%) |
P-value | 0.2806 | 0.4810 | ||
ER statusc
| ||||
Negative | 11 (20%) | 12 (8%) | 14 (20%) | 9 (6%) |
Positive | 44 (80%) | 148 (93%) | 55 (80%) | 131 (94%) |
P-value | 0.0098 | 0.0027 | ||
PgR statusc
| ||||
Negative | 16 (36%) | 48 (33%) | 20 (37%) | 43 (33%) |
Positive | 28 (64%) | 98 (67%) | 34 (63%) | 87 (67%) |
P-value | 0.6688 | 0.6072 |
Aromatase expression and clinical or radiological response to neoadjuvant letrozole or tamoxifen
Responses | Aromatase protein expression [n (%)] | |||
---|---|---|---|---|
Tumor epithelial aromatase | Stromal aromatase | |||
Negative | Positive | Negative | Positive | |
Clinical response
a
| ||||
Letrozole only | ||||
No | 6 (29%) | 24 (32%) | 11 (44%) | 18(26) |
Yes | 15 (71%) | 51 (68%) | 14 (56%) | 51(74) |
P-value | 0.7657 | 0.0984 | ||
Tamoxifen only | ||||
No | 12 (50%) | 37 (51%) | 13 (45%) | 34 (54%) |
Yes | 12 (50%) | 35 (49%) | 16 (55%) | 29 (46%) |
P-value | 0.9067 | 0.4177 | ||
Fused | ||||
No | 18 (40%) | 61 (41%) | 24 (44%) | 52 (39%) |
Yes | 27 (60%) | 86 (59%) | 30 (56%) | 80 (61%) |
P-value | 0.8587 | 0.5259 | ||
Mammo response
a
| ||||
Letrozole only | ||||
No | 13 (62%) | 47 (63%) | 17 (68%) | 42 (61%) |
Yes | 8 (38%) | 28 (37%) | 8 (32%) | 27 (39%) |
P-value | 0.9494 | 0.5297 | ||
Tamoxifen only | ||||
No | 19 (79%) | 54 (75%) | 23 (79%) | 48 (76%) |
Yes | 5 (21%) | 18 (25%) | 6 (21%) | 15 (24%) |
P-value | 0.6803 | 0.7418 | ||
Fused | ||||
No | 32 (71%) | 101 (69%) | 40 (74%) | 90 (68%) |
Yes | 13 (29%) | 46 (31%) | 14 (26%) | 42 (32%) |
P-value | 0.7604 | 0.4278 | ||
Ultrasound response
a
| ||||
Letrozole only | ||||
No | 12 (67%) | 39 (56%) | 16 (73%) | 34 (52%) |
Yes | 6 (33%) | 31 (44%) | 6 (27%) | 31 (48%) |
P-value | 0.4038 | 0.0959 | ||
Tamoxifen only | ||||
No | 13 (68%) | 44 (64%) | 15 (60%) | 41 (69%) |
Yes | 6 (32%) | 25 (36%) | 10 (60%) | 18 (31%) |
P-value | 0.7085 | 0.4016 | ||
Fused | ||||
No | 25 (68%) | 83 (60%) | 31 (66%) | 75 (60%) |
Yes | 12 (32%) | 56 (40%) | 16 (34%) | 49 (40%) |
P-value | 0.3845 | 0.5116 |
Ki67 [Geometric mean (95% CI)]a
| Aromatase protein expression | |||
---|---|---|---|---|
Cancer cells | Stromal cells | |||
Negative | Positive | Negative | Positive | |
Letrozole only | ||||
Pre | 5.54 (2.54–12.08) | 3.56 (2.47–5.14) | 3.64 (1.70–7.82) | 3.92 (2.69–5.72) |
Post | 0.70 (0.33–1.49) | 0.49 (0.31–0.75) | 0.88 (0.38–2.04) | 0.44 (0.29–0.68) |
P-valueb
| 0.0037 | 0.0001 | 0.0083 | 0.0001 |
Tamoxifen only | ||||
Pre | 5.97 (3.17–11.24) | 5.63 (4.18–7.58) | 7.75 (4.46–13.47) | 4.67 (3.39–6.44) |
Post | 1.72 (0.75–3.97) | 1.36 (0.88–2.09) | 1.61 (0.76–3.39) | 1.23 (0.77–1.95) |
P-valueb
| 0.0117 | 0.0001 | 0.0007 | 0.0001 |
Aromatase expression and relapse-free survival and breast cancer-specific survival
A | ||||||
---|---|---|---|---|---|---|
Factor definitions | No. of patients in each group | No. of events/No. of patients | Relapse-free survival | |||
Univariable analysis | Multivariate analysis | |||||
HR (95% CI) |
P
| HR (95% CI) |
P
| |||
Tumor sizea
(T1/2 vs. T3/4) | 138/33 | 47/171 | 2.7 (1.4–5.0) | 0.002 | 2.82 (1.36–5.85) | 0.006 |
Node status (Yes vs. No) | 90/69 | 44/159 | 3.9 (1.8–8.4) | 0.0005 | 3.44 (1.58–7.48) | 0.002 |
Ki67 level, per 2.7 fold increaseb
| 48/174 | 1.4 (1.2–1.6) | 0.0002 | 1.1 (1.02–1.09) | 0.003 | |
ER Allredc
(0.2 vs. 3–8) | 16/157 | 48/173 | 2.4 (1.0–5.3) | 0.04 | 2.74 (1.1–6.67) | 0.03 |
Aromatase statusd
(not present versus present) | 37/132 | 48/169 | 1.88 (1.01–3.47) | 0.04 | 2.34 (1.2–4.58) | 0.01 |
B | ||||||
---|---|---|---|---|---|---|
Factor definitions | No. of patients in each group | No. of events/No. of patients | Breast cancer-specific survival | |||
Univariable analysis | Multivariate analysis | |||||
HR (95% CI) |
P
| HR (95% CI) |
P
| |||
Tumor size (T1/2 vs. T3/4) | 138/33 | 24/171 | 3.5 (1.5–8.3) | 0.004 | 3.42 (1.21–9.66) | 0.02 |
Node status (Yes vs. No) | 90/69 | 22/159 | 4.6 (1.4–15.8) | 0.01 | 4.05 (1.14–14.38) | 0.03 |
Ki67 level, per 2.7 fold increase | 25/174 | 1.4 (1.1–1.7) | 0.009 | 1.05 (1.0–1.11) | 0.06 | |
ER Allred (0.2 vs. 3–8) | 16/157 | 25/173 | 4.3 (1.6–11.7) | 0.005 | 7.98 (2.58–24.7) | 0.0003 |
Aromatase status (not present versus present) | 37/132 | 24/169 | 2.82 (1.2–6.63) | 0.02 | 3.76 (1.42–9.98) | 0.008 |