Background
Methods
Study design and subject selection
Analysis of crown-like structures (CLS)
Sex-steroid hormone measurement
Statistical analysis
Results
Characteristics of the study population
Distribution of CD68 and CLS in postmenopausal breast adipose tissue
n (%) | No. of CD68-positive cells |
p value | No. of CD68-positive cells per 100 mm2 fat area |
p value | |
---|---|---|---|---|---|
Overall | 83 (100) | 150.0 (5–1237) | 13 (1–737) | ||
CLS-positive | 30 (36) | 250.5 (34–1237) | <0.001 | 20 (2–406) | 0.23 |
CLS-negative | 53 (64) | 113.0 (5–522) | 10 (1–737) | ||
ER-positive | |||||
CLS-positive | 21 (35) | 253.0 (34–1237) | <0.001 | 19 (3–140) | 0.69 |
CLS-negative | 39 (65) | 109.0 (5–481) | 12 (2–364) | ||
ER-negative | |||||
CLS-positive | 9 (39) | 188.0 (106–588) | 0.06 | 39 (2–406) | 0.16 |
CLS-negative | 14 (61) | 123.5 (6–522) | 10 (1–737) |
Relationship of breast cancer risk factors and tumor characteristics with number of CD68-positive cells and CLS among postmenopausal breast cancer cases
CLS-positive n (%) | CLS-negative n (%) | Unadjusted | Adjustedb
| ||||
---|---|---|---|---|---|---|---|
Patient characteristic |
p valuea
| OR | 95% CI | OR | 95% CI | ||
Age | 0.30 | ||||||
40–49 years | 1 (3.3) | 7 (13.0) | 0.34 | 0.04–3.20 | 0.31 | 0.03–3.12 | |
50–59 years | 8 (26.7) | 19 (35.2) | Reference | Reference | |||
60–69 years | 12 (40.0) | 18 (33.3) | 1.68 | 0.55–5.08 | 1.17 | 0.35–3.91 | |
≥70 years | 9 (30.0) | 10 (18.5) | 2.14 | 0.63–7.26 | 1.63 | 0.45–6.00 | |
BMI category |
0.03
| ||||||
Lean | 4 (14) | 19 (36) | Reference | Reference | |||
Overweight | 13 (43) | 23 (43) | 2.69 | 0.75–9.61 | 1.93 | 0.50–7.40 | |
Obese | 13 (43) | 11 (21) |
5.61
|
1.46–21.53
|
4.63
|
1.08–19.83
| |
Age at menarche | 0.28 | ||||||
<13 years | 9 (31) | 10 (19) | Reference | Reference | |||
≥13 years | 20 (69) | 43 (81) | 0.52 | 0.18–1.47 | 0.40 | 0.12–1.32 | |
Age at menopause | 0.09 | ||||||
<45 years | 2 (7) | 6 (11) | Reference | Reference | |||
45–49 years | 8 (27) | 25 (47) | 0.96 | 0.16–5.74 | 1.50 | 0.21–10.44 | |
50–54 years | 13 (43) | 18 (34) | 2.17 | 0.38–12.50 | 2.95 | 0.42–20.68 | |
≥55 years | 7 (23) | 4 (8) | 5.25 | 0.70–39.48 | 6.19 | 0.63–60.73 | |
Age at first birth | 1.00 | ||||||
Nulliparous | 5 (17) | 10 (19) | Reference | Reference | |||
<30 years | 20 (66) | 35 (66) | 1.14 | 0.34–3.82 | 1.08 | 0.28–4.17 | |
≥30 years | 5 (17) | 8 (15) | 1.25 | 0.27–5.89 | 1.42 | 0.26–7.93 | |
Family history of breast cancer | 0.53 | ||||||
No | 24 (80) | 46 (87) | Reference | Reference | |||
Yes | 6 (20) | 7 (13) | 1.64 | 0.50–5.44 | 2.91 | 0.71–11.96 | |
Benign breast disease | 0.74 | ||||||
No | 25 (89) | 44 (85) | Reference | Reference | |||
Yes | 3 (11) | 8 (15) | 0.66 | 0.16–2.72 | 1.09 | 0.22–5.35 | |
Tumor size | 1.00 | ||||||
≤2 cm | 15 (52) | 26 (49) | Reference | Reference | |||
>2 cm | 14 (48) | 27 (51) | 0.90 | 0.36–2.22 | 0.62 | 0.22–1.75 | |
Nodal status | 0.22 | ||||||
No | 20 (67) | 26 (49) | Reference | Reference | |||
1–3 | 7 (23) | 15 (28) | 0.61 | 0.21–1.77 | 0.38 | 0.11–1.41 | |
≥4 | 3 (10) | 12 (23) | 0.33 | 0.08–1.31 | 0.44 | 0.10–2.00 | |
ER status | 0.80 | ||||||
Positive | 21 (70) | 39 (74) | Reference | Reference | |||
Negative | 9 (30) | 14 (26) | 1.19 | 0.44–3.22 | 1.09 | 0.35–3.39 | |
PR status | 0.80 | ||||||
Positive | 21 (70) | 39 (74) | Reference | Reference | |||
Negative | 9 (30) | 14 (26) | 1.19 | 0.44–3.22 | 1.09 | 0.35–3.39 | |
Diagnosis | 0.65 | ||||||
In situ and invasive | 17 (57) | 33 (62) | Reference | Reference | |||
Invasive only | 13 (43) | 20 (38) | 1.26 | 0.51–3.14 | 1.22 | 0.45–3.29 | |
Grade | 0.70 | ||||||
Well differentiated | 4 (13) | 11 (21) | Reference | Reference | |||
Moderately differentiated | 19 (64) | 29 (55) | 1.80 | 0.50–6.49 | 1.32 | 0.33–5.24 | |
Poorly differentiated | 7 (23) | 13 (24) | 1.48 | 0.34–6.42 | 1.68 | 0.33–8.55 |
Relationship of CLS presence with sex-steroid hormone levels in adipose tissue and serum of postmenopausal breast cancer cases
Tissue (pg/g) | Blood (pg/ml) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusteda
| Unadjusted | Adjusteda
| |||||||||
CLS-positive | CLS-negative | OR | 95% CI | OR | 95% CI | CLS-positive | CLS-negative | OR | 95% CI | OR | 95% CI | |
Individual hormones
| ||||||||||||
Androstenedione | ||||||||||||
Tertile 3 | 7 | 21 | Reference | Reference | 7 | 21 | Reference | Reference | ||||
Tertile 2 | 10 | 17 | 1.77 | 0.84–8.07 | 1.67 | 0.47–5.93 | 11 | 16 | 2.06 | 0.65–6.51 | 0.46 | 0.13–1.62 |
Tertile 1 | 13 | 15 | 2.60 | 0.84–8.07 | 3.13 | 0.88–11.18 | 12 | 16 | 2.25 | 0.72–7.01 | 0.95 | 0.28–3.20 |
p trend | 0.28 | 0.08 | 0.17 | 0.23 | ||||||||
Testosterone | ||||||||||||
Tertile 3 | 9 | 19 | Reference | Reference | 7 | 17 | Reference | Reference | ||||
Tertile 2 | 13 | 14 | 1.96 | 0.66–5.86 | 2.29 | 0.66–7.91 | 10 | 16 | 1.79 | 0.56–5.74 | 1.86 | 0.50–7.00 |
Tertile 1 | 8 | 20 | 0.85 | 0.27–2.64 | 1.20 | 0.30–4.80 | 13 | 19 | 2.32 | 0.75–7.19 | 3.33 | 0.91–12.20 |
p trend | 0.78 | 0.70 | 0.15 | 0.07 | ||||||||
Estrone | ||||||||||||
Tertile 3 | 10 | 18 | Reference | Reference | 10 | 17 | Reference | Reference | ||||
Tertile 2 | 15 | 12 | 2.25 | 0.76–6.65 |
4.35
|
1.06–17.86
| 10 | 16 | 1.06 | 0.35–3.23 | 1.83 | 0.46–7.22 |
Tertile 1 | 5 | 23 | 0.39 | 0.11–1.35 | 1.01 | 0.20–5.10 | 9 | 19 | 0.81 | 0.27–2.45 | 2.16 | 0.53–8.79 |
p trend | 0.17 | 0.90 | 0.70 | 0.29 | ||||||||
Estradiol | ||||||||||||
Tertiles 3 | 12 | 15 | Reference | Reference | 10 | 17 | Reference | Reference | ||||
Tertiles 2 | 9 | 18 | 0.63 | 0.21–1.88 | 0.69 | 0.20–2.39 | 8 | 14 | 0.97 | 0.30–3.12 | 1.41 | 0.38–5.30 |
Tertiles 1 | 8 | 20 | 0.50 | 0.16–1.53 | 0.61 | 0.17–2.20 | 12 | 21 | 0.97 | 0.34–2.79 | 1.49 | 0.44–5.08 |
p trend | 0.22 | 0.46 | 0.96 | 0.53 | ||||||||
Hormone ratios
| ||||||||||||
Estrone:Androstenedione | ||||||||||||
Tertiles 3 | 17 | 11 | Reference | Reference | 13 | 14 | Reference | Reference | ||||
Tertiles 2 | 9 | 18 |
0.32
|
0.11–0.97
| 0.30 | 0.08–1.17 | 10 | 17 | 0.63 | 0.21–1.88 | 1.00 | 0.29–3.47 |
Tertiles 1 | 4 | 24 |
0.11
|
0.03–0.40
|
0.12
|
0.03–0.59
| 6 | 21 |
0.31
|
0.10–1.00
| 0.59 | 0.15–2.29 |
p trend |
<0.01
|
0.01
| 0.05 | 0.46 | ||||||||
Estradiol:Testosterone | ||||||||||||
Tertiles 3 | 12 | 16 | Reference | Reference | 17 | 12 | Reference | Reference | ||||
Tertiles 2 | 9 | 18 | 0.67 | 0.22–1.99 | 0.46 | 0.13–1.64 | 7 | 18 |
0.28
|
0.09–0.86
| 0.30 | 0.08–1.22 |
Tertiles 1 | 8 | 19 | 0.56 | 0.18–1.71 | 0.38 | 0.10–1.39 | 6 | 21 |
0.20
|
0.06–0.65
|
0.18
|
0.04–0.72
|
p trend | 0.31 | 0.15 |
0.01
|
0.02
|