Correlation between Androgen Receptor Expression in Luminal B (HER–2 Negative) Breast Cancer and Disease Outcomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Specimen Preparation and Staining
2.3. Immunohistochemistry (IHC) and Fluorescent In Situ Hybridization (FISH)
2.4. Neoadjuvant Treatment Regimen and Evaluation Criteria
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Prognosis–Related Risk Factors in the Overall Luminal B (HER–2 Negative) Breast Cancer Population
3.3. Prognosis–Related AR Cutoff Values in the Overall Luminal B (HER–2 Negative) Breast Cancer Population
3.4. Prognosis–Related Risk Factors in the Non–pCR Population of Luminal B (HER–2 Negative) Breast Cancer Who Underwent Neoadjuvant Therapy
3.5. Prognosis–Related AR/ER and Residual Tumor Ki67 Cutoff Values in the Non–pCR Population of Luminal B (HER–2 Negative) Breast Cancer Who Underwent Neoadjuvant Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Baseline Characteristics | Total | Neoadjuvant Chemotherapy | Non–Neoadjuvant Chemotherapy | p Value | |
---|---|---|---|---|---|
985 (100%) | 143 (14.5%) | 842 (85.5%) | |||
Sex | Female | 978 (99.3%) | 143 (100%) | 835 (99.2%) | 0.602 |
Male | 7 (0.7%) | 0 (0%) | 7 (0.8%) | ||
Age | ≤40 | 93 (9.5%) | 28 (19.6%) | 65 (7.7%) | <0.001 |
>40 | 891 (90.5%) | 115 (80.4%) | 776 (92.3%) | ||
BMI | <24.0 | 439 (45.8%) | 56 (39.7%) | 383 (46.8%) | 0.118 |
≥24.0 | 520 (54.2%) | 85 (60.3%) | 435 (53.2%) | ||
Menopause | No | 352 (38.1%) | 73 (52.5%) | 279 (35.5%) | <0.001 |
Yes | 573 (61.9%) | 66 (47.5%) | 507 (64.5%) | ||
T stage | T0–2 | 940 (85.8%) | 118 (84.9%) | 822 (97.6%) | <0.001 |
T3–4 | 31 (14.2%) | 11 (15.1%) | 20 (2.4%) | ||
N stage | N0 | 556 (57.1%) | 31 (22.3%) | 525 (62.9%) | <0.001 |
N+ | 418 (42.9%) | 108 (77.7%) | 310 (37.1%) | ||
Grade | G1–2 | 750 (77.2%) | 83 (59.7%) | 667 (80.2%) | <0.001 |
G3 | 221 (22.8%) | 56 (40.3%) | 165 (19.8%) | ||
CNB ER | 1–10% | 21 (2.1%) | 9 (6.3%) | 12 (1.4%) | <0.001 |
11–30% | 17 (1.7%) | 7 (4.9%) | 10 (1.2%) | ||
≥30% | 947 (96.1%) | 127 (88.8%) | 820 (97.4%) | ||
CNB PR | 0–10% | 286 (29%) | 53 (37.1%) | 233 (27.7%) | 0.032 |
11–30% | 90 (9.1%) | 12 (8.4%) | 78 (9.3%) | ||
≥30% | 609 (61.8%) | 78 (54.4%) | 531 (63.1%) | ||
CNB HER–2 | IHC − | 347 (35.3%) | 41 (28.9%) | 306 (36.3%) | 0.085 |
IHC + ~ ++ | 637 (64.7%) | 101 (71.1%) | 536 (63.7%) | ||
CNB AR | 0 | 22 (2.2%) | 11 (7.7%) | 11 (1.3%) | <0.001 |
1–64% | 140 (14.2%) | 39 (27.3%) | 101 (12.0%) | ||
65–89% | 217 (22.0%) | 21 (14.7%) | 196 (23.3%) | ||
≥90% | 606 (61.5%) | 72 (50.3%) | 534 (63.4%) | ||
AR/ER | ≤1.00 | 840 (85.3%) | 121 (84.6%) | 719 (85.4%) | 0.809 |
>1.00 | 145 (14.7%) | 22 (15.4%) | 123 (14.6%) | ||
AR/PR | ≤1.00 | 442 (44.9%) | 59 (41.3%) | 383 (45.5%) | 0.347 |
>1.00 | 543 (55.1%) | 84 (58.7%) | 459 (54.5%) | ||
CNB Ki67 | 0–10% | 54 (5.5%) | 1 (0.7%) | 53 (6.3%) | <0.001 |
11–30% | 629 (63.9%) | 47 (32.9%) | 582 (69.1%) | ||
≥30% | 302 (30.7%) | 95 (66.4%) | 207 (24.6%) | ||
Median follow–up duration (month) | 42(4–101) | 46 (4–101) | 42 (8–79) | ||
Occurrence of DFS | No | 830 (90.9%) | 101 (73.2%) | 729 (94.1%) | <0.001 |
Yes | 83 (9.1%) | 37 (26.8%) | 46 (5.9%) | ||
Occurrence of OS | No | 880 (96.8%) | 124 (92.5%) | 756 (97.5%) | 0.002 |
Yes | 29 (3.2%) | 10 (7.5%) | 19 (2.5%) |
Clinicopathologic Feature | No. of Patients (%) | |
---|---|---|
Neoadjuvant therapy | Chemotherapy | 134 (93.7%) |
Anthracycline plus taxane | 126 (88.1%) | |
Other chemotherapy | 8 (5.6%) | |
Endocrine therapy | 9 (6.3%) | |
Miller–Payne stage | G1 | 31 (21.7%) |
G2 | 10 (7%) | |
G3 | 50 (35%) | |
G4 | 32 (22.4%) | |
G5 | 7 (4.9%) | |
Unknown | 13 (9.1%) | |
pCR | No | 136 (95.1%) |
Yes | 7 (4.9%) | |
ypT stage | ypT0 | 7 (4.9%) |
ypT1–2 | 125 (87.4%) | |
ypT3–4 | 11 (7.7%) | |
ypN stage | ypN0 | 46 (32.2%) |
ypN+ | 96 (67.1%) | |
Unknown | 1 (0.7%) | |
ER of residual tumor | 1–10% | 16 (11.2%) |
11–30% | 6 (1.2%) | |
≥30% | 111 (77.6%) | |
pCR/unknown | 10 (7.0%) | |
PR of residual tumor | 1–10% | 68 (47.6%) |
11–30% | 18 (12.6%) | |
≥30% | 47 (32.9%) | |
pCR/unknown | 10 (7.0%) | |
Ki67 of residual tumor | Ki67 ≤ 20% | 84 (58.7%) |
Ki67 > 20% | 48 (33.6%) | |
pCR/ unknown | 11 (7.7%) | |
ΔKi67 | Large decrease | 31 (21.7%) |
Medium decrease | 36 (25.2%) | |
Slight decrease/no change | 48 (33.6%) | |
Increase | 15 (10.5%) | |
pCR/unknown | 13 (9.1%) |
Step | Factors Included | B | SE | Wald | HR (95% CI) | p Value | |
---|---|---|---|---|---|---|---|
Step 1 | Age | ≤40 | reference | ||||
>40 | −0.696 | 0.3 | 5.374 | 0.499 (0.277–0.898) | 0.02 | ||
Baseline T stage | T0–2 | reference | |||||
T3–4 | 0.923 | 0.347 | 7.05 | 2.516 (1.273–4.971) | 0.008 | ||
Baseline N stage | N0 | reference | |||||
N+ | 0.748 | 0.272 | 7.587 | 2.114 (1.241–3.6) | 0.006 | ||
Grade | G1–2 | reference | |||||
G3 | 0.726 | 0.262 | 7.694 | 2.067 (1.237–3.454) | 0.006 | ||
CNB ER | 1–10% | 1.283 | reference | 0.526 | |||
11–30% | 0.629 | 0.88 | 0.51 | 1.875 (0.334–10.523) | 0.475 | ||
≥30% | 0.026 | 0.795 | 0.001 | 1.027 (0.216–4.875) | 0.973 | ||
CNB PR | 0–10% | 1.647 | reference | 0.439 | |||
11–30% | −0.549 | 0.44 | 1.558 | 0.578 (0.244–1.367) | 0.212 | ||
≥30% | −0.041 | 0.327 | 0.015 | 0.96 (0.506–1.823) | 0.901 | ||
CNB HER–2 | IHC − | reference | |||||
IHC + ~ ++ | −0.236 | 0.254 | 0.864 | 0.79 (0.481–1.299) | 0.353 | ||
CNB AR | 0–89% | reference | |||||
≥90% | −0.555 | 0.254 | 4.767 | 0.574 (0.349–0.945) | 0.029 | ||
AR/ER | ≤1.00 | reference | |||||
>1.00 | 0.326 | 0.321 | 1.037 | 1.386 (0.739–2.598) | 0.309 | ||
AR/PR | ≤1.00 | reference | |||||
>1.00 | 0.356 | 0.306 | 1.355 | 1.427 (0.784–2.598) | 0.244 | ||
CNB Ki67 | 0–10% | 0.8 | reference | 0.67 | |||
11–30% | −0.379 | 0.631 | 0.36 | 0.685 (0.199–2.36) | 0.549 | ||
≥30% | −0.182 | 0.653 | 0.078 | 0.833 (0.232–2.994) | 0.78 | ||
Neoadjuvant therapy | No | reference | |||||
Yes | 0.56 | 0.282 | 3.932 | 1.75 (1.007–3.042) | 0.047 | ||
Step 7 | Age | ≤40 | reference | ||||
>40 | −0.665 | 0.29 | 5.268 | 0.514 (0.292–0.907) | 0.022 | ||
Baseline T stage | T0–2 | reference | |||||
T3–4 | 0.873 | 0.329 | 7.036 | 2.395 (1.256–4.565) | 0.008 | ||
Baseline N stage | N0 | reference | |||||
N+ | 0.679 | 0.266 | 6.52 | 1.972 (1.171–3.32) | 0.011 | ||
Grade | G1–2 | reference | |||||
G3 | 0.722 | 0.243 | 8.848 | 2.059 (1.279–3.313) | 0.003 | ||
CNB AR | 0–89% | reference | |||||
≥90% | −0.555 | 0.235 | 5.575 | 0.574 (0.362–0.91) | 0.018 | ||
Neoadjuvant therapy | No | reference | |||||
Yes | 0.675 | 0.266 | 6.422 | 1.964 (1.165–3.31) | 0.011 |
Step | Factors Included | B | SE | Wald | HR (95% CI) | p Value | |
---|---|---|---|---|---|---|---|
Step 1 | Age | ≤40 | |||||
>40 | 0.921 | 0.796 | 1.341 | 2.513 (0.528–11.947) | 0.247 | ||
Baseline T stage | T0–2 | ||||||
T3–4 | 1.077 | 0.599 | 3.231 | 2.937 (0.907–9.505) | 0.072 | ||
Baseline N stage | N0 | ||||||
N+ | 0.97 | 0.45 | 4.638 | 2.637 (1.091–6.375) | 0.031 | ||
Grade | G1–2 | ||||||
G3 | 0.885 | 0.431 | 4.221 | 2.424 (1.042–5.64) | 0.04 | ||
CNB ER | 1–10% | 0.857 | 0.652 | ||||
11–30% | 0.619 | 1.375 | 0.203 | 1.857 (0.126–27.486) | 0.652 | ||
≥30% | −0.229 | 1.215 | 0.035 | 0.796 (0.074–8.602) | 0.851 | ||
CNB PR | 0–10% | 0.343 | 0.842 | ||||
11–30% | −0.283 | 0.645 | 0.193 | 0.753 (0.213–2.665) | 0.66 | ||
≥30% | −0.311 | 0.61 | 0.26 | 0.733 (0.222–2.423) | 0.61 | ||
CNB HER–2 | IHC − | ||||||
IHC + ~ ++ | −0.854 | 0.405 | 4.443 | 0.426 (0.193–0.942) | 0.035 | ||
CNB AR | 0–89% | ||||||
≥90% | −1.034 | 0.431 | 5.755 | 0.356 (0.153–0.828) | 0.016 | ||
AR/ER | ≤1.00 | ||||||
>1.00 | −0.638 | 0.693 | 0.845 | 0.529 (0.136–2.058) | 0.358 | ||
AR/PR | ≤1.00 | ||||||
>1.00 | −0.114 | 0.546 | 0.043 | 0.893 (0.306–2.602) | 0.835 | ||
CNB Ki67 | 0–10% | 0.053 | 0.974 | ||||
11–30% | −0.059 | 1.078 | 0.003 | 0.943 (0.114–7.804) | 0.956 | ||
≥30% | 0.044 | 1.12 | 0.002 | 1.045 (0.116–9.383) | 0.969 | ||
Neoadjuvant therapy | No | ||||||
Yes | 0.013 | 0.489 | 0.001 | 1.013 (0.389–2.639) | 0.979 | ||
Step 8 | Baseline T stage | T0–2 | |||||
T3–4 | 1.045 | 0.518 | 4.065 | 2.842 (1.03–7.847) | 0.044 | ||
Baseline N stage | N0 | ||||||
N+ | 0.921 | 0.43 | 4.588 | 2.511 (1.081–5.831) | 0.032 | ||
Grade | G1–2 | ||||||
G3 | 0.872 | 0.39 | 4.982 | 2.391 (1.112–5.139) | 0.026 | ||
CNB HER–2 | IHC − | ||||||
IHC + ~ ++ | −0.825 | 0.389 | 4.488 | 0.438 (0.204–0.94) | 0.034 | ||
CNB AR | 0–89% | ||||||
≥90% | −1.163 | 0.401 | 8.424 | 0.312 (0.142–0.685) | 0.004 |
Group | DFS | OS |
---|---|---|
pCR | 85.71% | 100.00% |
non–pCR | 73.53% | 92.65% |
p value | 0.741 | >0.999 |
Factors Included | B | SE | Wald | HR (95% CI) | p Value | |
---|---|---|---|---|---|---|
Age | ≤40 | reference | ||||
>40 | −0.411 | 0.481 | 0.731 | 0.663 (0.258–1.701) | 0.393 | |
Baseline T stage | T0–2 | reference | ||||
T3–4 | 1.266 | 0.571 | 4.923 | 3.547 (1.159–10.854) | 0.027 | |
Baseline N stage | N0 | reference | ||||
N+ | −0.009 | 0.89 | 0 | 0.991 (0.173–5.671) | 0.992 | |
Grade | G1–2 | reference | ||||
G3 | 0.414 | 0.626 | 0.436 | 1.512 (0.443–5.157) | 0.509 | |
CNB ER | 1–10% | 1.273 | reference | 0.529 | ||
11–30% | 1.686 | 1.498 | 1.266 | 5.396 (0.286–101.71) | 0.261 | |
≥30% | 1.49 | 1.674 | 0.793 | 4.439 (0.167–118.05) | 0.373 | |
CNB PR | 0–10% | 1.481 | reference | 0.477 | ||
11–30% | −1.007 | 0.926 | 1.183 | 0.365 (0.06–2.242) | 0.277 | |
≥30% | −0.806 | 0.801 | 1.011 | 0.447 (0.093–2.148) | 0.315 | |
CNB HER–2 | IHC − | reference | ||||
IHC + ~ ++ | −0.86 | 0.571 | 2.269 | 0.423 (0.138–1.295) | 0.132 | |
CNB AR | <65% | reference | ||||
≥65% | −0.041 | 0.572 | 0.005 | 0.96 (0.313–2.946) | 0.943 | |
AR/ER | ≤1.00 | reference | ||||
>1.00 | 1.683 | 0.739 | 5.183 | 5.381 (1.264–22.91) | 0.023 | |
AR/PR | ≤1.00 | reference | ||||
>1.00 | −0.82 | 0.611 | 1.8 | 0.441 (0.133–1.459) | 0.18 | |
CNB Ki67 | 0–10% | 2.013 | reference | 0.365 | ||
11–30% | 5.187 | 85.207 | 0.004 | 178.85 (0–6.035 × 1074) | 0.951 | |
≥30% | 4.31 | 85.21 | 0.003 | 74.467 (0–2.528 × 1074) | 0.96 | |
ypT stage | T0–2 | reference | ||||
T3–4 | 0.969 | 0.884 | 1.201 | 2.637 (0.466–14.925) | 0.273 | |
ypN stage | ypN0 | reference | ||||
ypN+ | −0.046 | 0.761 | 0.004 | 0.955 (0.215–4.241) | 0.951 | |
ER of residual tumor | 1–10% | 2.709 | reference | 0.258 | ||
11–30% | −1.385 | 1.556 | 0.792 | 0.25 (0.012–5.283) | 0.373 | |
≥30% | 0.695 | 1.181 | 0.346 | 2.004 (0.198–20.302) | 0.556 | |
PR of residual tumor | 1–10% | 0.614 | reference | 0.736 | ||
11–30% | −0.08 | 0.812 | 0.01 | 0.923 (0.188–4.532) | 0.921 | |
≥30% | 0.395 | 0.625 | 0.4 | 1.485 (0.436–5.052) | 0.527 | |
HER–2 of residual tumor | − | reference | ||||
+ ~ ++ | 0.241 | 0.369 | 0.427 | 1.273 (0.617–2.626) | 0.513 | |
Ki67 of residual tumor | Ki67 ≤ 20% | reference | ||||
Ki67 > 20% | 1.607 | 0.676 | 5.658 | 4.988 (1.327–18.748) | 0.017 | |
ΔKi67 | Large decrease | 5.641 | reference | 0.13 | ||
Medium decrease | 0.577 | 0.834 | 0.478 | 1.78 (0.347–9.132) | 0.489 | |
Slight decrease/no change | −0.079 | 0.89 | 0.008 | 0.924 (0.162–5.286) | 0.929 | |
Increase | −2.241 | 1.439 | 2.425 | 0.106 (0.006–1.785) | 0.119 |
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Yang, F.; Li, J.; Zhang, H.; Zhang, S.; Ye, J.; Cheng, Y.; Liu, Q.; Xin, L.; Xiang, H.; Liu, Y.; et al. Correlation between Androgen Receptor Expression in Luminal B (HER–2 Negative) Breast Cancer and Disease Outcomes. J. Pers. Med. 2022, 12, 1988. https://doi.org/10.3390/jpm12121988
Yang F, Li J, Zhang H, Zhang S, Ye J, Cheng Y, Liu Q, Xin L, Xiang H, Liu Y, et al. Correlation between Androgen Receptor Expression in Luminal B (HER–2 Negative) Breast Cancer and Disease Outcomes. Journal of Personalized Medicine. 2022; 12(12):1988. https://doi.org/10.3390/jpm12121988
Chicago/Turabian StyleYang, Fan, Jiayi Li, Hong Zhang, Shuang Zhang, Jingming Ye, Yuanjia Cheng, Qian Liu, Ling Xin, Hongyu Xiang, Yinhua Liu, and et al. 2022. "Correlation between Androgen Receptor Expression in Luminal B (HER–2 Negative) Breast Cancer and Disease Outcomes" Journal of Personalized Medicine 12, no. 12: 1988. https://doi.org/10.3390/jpm12121988
APA StyleYang, F., Li, J., Zhang, H., Zhang, S., Ye, J., Cheng, Y., Liu, Q., Xin, L., Xiang, H., Liu, Y., Duan, X., & Xu, L. (2022). Correlation between Androgen Receptor Expression in Luminal B (HER–2 Negative) Breast Cancer and Disease Outcomes. Journal of Personalized Medicine, 12(12), 1988. https://doi.org/10.3390/jpm12121988