Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Immunohistochemistry
2.2. Baseline Data
2.3. Statistical Analysis
3. Results
Prognostic Indicators according to HER2+ BC Subtypes
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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IHC BC Subtypes | Number | % | HER2 IHC Intensity | |
---|---|---|---|---|
2+ | 3+ | |||
Luminal B HER2 + AR+ | 396 | 57.0 | 126 | 270 |
Luminal B HER2 + AR− | 18 | 2.6 | 6 | 12 |
HER2 + AR+ | 241 | 34.7 | 22 | 219 |
HER2 + AR− | 40 | 5.7 | 5 | 35 |
Variables | n = 695 | |
---|---|---|
Median (IQR) age, years | 58 (49–68) | |
Age (year), n (%) | <58 | 332 (47.8) |
≥58 | 363 (52.2) | |
Site, n (%) | Left | 396 (57.2) |
Right | 296 (42.8) | |
Histologic type, n (%) | Ductal | 590 (85.0) |
Apocrine | 39 (5.6) | |
Lobular | 30 (4.3) | |
Micropapillary/papillary | 15 (2.2) | |
Mixed (ductal + lobular) | 13 (1.9) | |
Mucinous | 7 (1.0) | |
Histologic grade, n (%) | G2 | 112 (16.3) |
G3 | 575 (83.7) | |
Pathological tumor size, n (%) | pT0 * | 53 (8.5) |
pT1 | 203 (32.6) | |
pT2 | 288 (46.2) | |
pT3 | 27 (4.3) | |
pT4 | 52 (8.4) | |
Pathological lymph node status, n (%) | pN0 | 321 (55.9) |
pN1 | 134 (23.3) | |
pN2 | 73 (12.7) | |
pN3 | 46 (8.0) | |
Lymph node ratio, n (%) | ≤0.20 | 400 (72.3) |
0.21–0.65 | 106 (19.2) | |
>0.65 | 47 (8.5) | |
Prognostic stage, n (%) | I | 249 (40.8) |
II | 174 (28.5) | |
III | 134 (21.9) | |
IV | 54 (8.8) | |
Metastasis, n (%) | 54 (7.8) | |
Proliferation index (Ki-67), n (%) | <14% | 9 (1.3) |
≥14% | 686 (98.7) | |
PR expression, n (%) | <10% | 455 (65.5) |
≥10% | 240 (34.5) | |
ER expression, n (%) | <10% | 281 (40.4) |
≥10% | 414 (59.6) | |
AR expression, n (%) | <10% | 59 (8.5) |
≥10% | 636 (91.5) | |
HER2 expression, n (%) | 2+ | 159 (22.9) |
3+ | 536 (77.1) | |
Mortality, n (%) | 99 (14.2) |
AR− (n = 58) | AR+ (n = 637) | p-Value | ||
---|---|---|---|---|
Median (IQR) age, years | 55 (44–68) | 59 (49–68) | 0.045 | |
Age (year), n (%) | <50 | 23 (39.7) | 161 (25.3) | 0.020 |
≥50 | 35 (60.3) | 476 (74.7) | ||
Site, n (%) | Left | 32 (55.2) | 364 (57.4) | 0.740 |
Right | 26 (44.8) | 270 (42.3) | ||
Histologic type, n (%) | CDI | 52 (89.7) | 538 (84.6) | 0.770 |
CLI | 1 (1.7) | 29 (4.6) | ||
CDI + CLI | 0 (0.0) | 13 (2.0) | ||
Apocrine | 3 (5.2) | 36 (5.7) | ||
Micropapillary + papillary | 1 (1.7) | 14 (2.2) | ||
Mucinous | 1 (1.7) | 6 (0.9) | ||
Histologic grade, n (%) | G2 | 3 (5.2) | 109 (17.3) | 0.020 |
G3 | 55 (94.8) | 520 (82.7) | ||
Pathological tumor size, n (%) | pT0 * | 4 (7.6) | 49 (8.6) | 0.020 |
pT1 | 11 (20.8) | 192 (33.7) | ||
pT2 | 25 (47.2) | 263 (46.2) | ||
pT3 | 7 (13.2) | 20 (3.5) | ||
pT4 | 6 (11.3) | 45 (7.9) | ||
Pathological lymph node status, n (%) | pN0 | 20 (46.5) | 301 (56.7) | 0.430 |
pN1 | 14 (32.6) | 120 (22.6) | ||
pN2 | 5 (11.6) | 68 (12.8) | ||
pN3 | 4 (9.3) | 42 (7.9) | ||
Lymph node ratio, n (%) | ≤0.20 | 26 (65.0) | 374 (72.9) | 0.470 |
0.21–0.65 | 10 (25.0) | 96 (18.7) | ||
>0.65 | 4 (10.0) | 43 (8.4) | ||
Prognostic stage, n (%) | I | 8 (16.3) | 241 (42.8) | 0.001 |
II | 22 (44.9) | 152 (27.0) | ||
III | 13 (26.5) | 122 (21.7) | ||
IV | 6 (12.2) | 48 (8.5) | ||
Metastasis, n (%) | 6 (10.3) | 48 (7.5) | 0.440 | |
Proliferation index (Ki-67), n (%) | <14% | 0 (0.0) | 9 (1.4) | 1.000 |
≥14% | 58 (100.0) | 627 (98.6) | ||
ER expression, n (%) | <10% | 40 (69.0) | 241 (37.8) | <0.0001 |
≥10% | 18 (31.0) | 396 (62.2) | ||
PR expression, n (%) | <10% | 51 (87.9) | 404 (63.4) | <0.0001 |
≥10% | 7 (12.1) | 233 (36.6) | ||
AR expression, n (%) | <10% | 57 (98.3) | 2 (0.3) | <0.0001 |
≥10% | 1 (1.7) | 635 (99.7) | ||
HER2 expression, n (%) | 2+ | 11 (19.0) | 148 (23.2) | 0.680 |
3+ | 48 (81.0) | 489 (76.8) | ||
Mortality, n (%) | 12 (20.7) | 87 (13.7) | 0.140 |
LB HER2+ AR− (n = 18) | LB HER2+ AR+ (n = 396) | HER2+ AR− (n = 40) | HER2+ AR+ (n = 241) | p-Value | ||
---|---|---|---|---|---|---|
Median (IQR) age, years | 53.5 (41–62) | 59 (48–69) | 55 (45–70) | 59 (50–68) | 0.160 | |
Age (year), n (%) | <50 | 8 (44.4) | 110 (27.8) | 15 (37.5) | 51 (21.2) | 0.030 |
≥50 | 10 (55.6) | 286 (72.2) | 25 (62.5) | 190 (78.8) | ||
Site, n (%) | Left | 11 (61.1) | 230 (58.4) | 21 (52.5) | 134 (55.8) | 0.870 |
Right | 7 (38.9) | 164 (41.6) | 19 (47.5) | 106 (44.2) | ||
Histologic type, n (%) | CDI | 16 (88.9) | 338 (85.4) | 36 (90.0) | 200 (83.3) | <0.0001 |
CLI | 1 (5.6) | 25 (6.3) | 0 (0.0) | 4 (1.7) | ||
CDI + CLI | 0 (0.0) | 10 (2.5) | 0 (0.0) | 3 (1.3) | ||
Apocrine | 1 (5.6) | 8 (2.0) | 2 (5.0) | 28 (11.7) | ||
Micropapillary + papillary | 0 (0.0) | 11 (2.7) | 1 (2.5) | 3 (1.3) | ||
Mucinous | 0 (0.0) | 4 (1.0) | 1 (2.5) | 2 (0.8) | ||
Histologic grade, n (%) | G2 | 1 (5.6) | 100 (25.5) | 2 (5.0) | 9 (3.8) | <0.0001 |
G3 | 17 (94.4) | 292 (74.5) | 38 (95.0) | 228 (96.2) | ||
Pathological tumor size, n (%) | pT0 * | 2 (12.5) | 20 (5.7) | 2 (5.4) | 29 (13.2) | 0.007 |
pT1 | 4 (25.0) | 127 (36.3) | 7 (18.9) | 65 (29.6) | ||
pT2 | 6 (37.5) | 162 (46.3) | 19 (51.4) | 101 (45.9) | ||
pT3 | 2 (12.5) | 15 (4.3) | 5 (13.5) | 5 (2.3) | ||
pT4 | 2 (12.5) | 26 (7.4) | 4 (10.8) | 20 (9.1) | ||
Pathological lymph node status, n (%) | pN0 | 6 (40.0) | 182 (55.8) | 14 (50.0) | 119 (58.1) | 0.570 |
pN1 | 4 (26.7) | 75 (23.0) | 10 (35.7) | 45 (22.0) | ||
pN2 | 3 (20.0) | 46 (14.1) | 2 (7.1) | 22 (10.7) | ||
pN3 | 2 (13.3) | 23 (7.1) | 2 (7.1) | 19 (9.3) | ||
Lymph node ratio, n (%) | ≤0.20 | 7 (50.0) | 227 (70.9) | 19 (73.1) | 147 (76.2) | 0.300 |
0.21–0.65 | 6 (42.9) | 64 (20.0) | 4 (15.4) | 32 (16.6) | ||
>0.65 | 1 (7.1) | 29 (9.1) | 3 (11.5) | 14 (7.3) | ||
Prognostic stage, n (%) | I | 6 (35.3) | 193 (55.5) | 2 (6.3) | 48 (22.3) | <0.0001 |
II | 4 (23.5) | 64 (18.4) | 18 (56.3) | 88 (40.9) | ||
III | 4 (23.5) | 60 (17.2) | 9 (28.1) | 62 (28.8) | ||
IV | 3 (17.7) | 31 (8.9) | 3 (9.4) | 17 (7.9) | ||
Metastasis, n (%) | 3 (16.7) | 32 (8.1) | 3 (7.5) | 16 (6.6) | 0.400 | |
Proliferation index (Ki-67), n (%) | <20% | 1 (5.6) | 30 (7.6) | 0 (0.0) | 11 (5.0) | 0.180 |
≥20% | 17 (94.4) | 366 (92.4) | 40 (100.0) | 229 (95.0) | ||
<14% | 0 (0.0) | 6 (1.5) | 0 (0.0) | 3 (1.2) | 1.000 | |
≥14% | 18 (100.0) | 390 (98.5) | 40 (100.0) | 238 (98.8) | ||
ER expression, n (%) | <10% | 0 (0.0) | 0 (0.0) | 40 (100.0) | 241 (100.0) | <0.0001 |
≥10% | 18 (100.0) | 396 (100.0) | 0 (0.0) | 0 (0.0) | ||
PR expression, n (%) | <10% | 11 (61.1) | 166 (41.9) | 40 (100.0) | 238 (98.8) | <0.0001 |
≥10% | 7 (38.9) | 230 (58.1) | 0 (0.0) | 3 (1.2) | ||
AR expression, n (%) | <10% | 17 (94.4) | 0 (0.0) | 40 (100.0) | 2 (0.8) | <0.0001 |
≥10% | 1 (5.6) | 396 (100.0) | 0 (0.0) | 239 (99.2) | ||
HER2 expression, n (%) | 2+ | 6 (33.3) | 126 (31.8) | 5 (12.5) | 22 9.1) | <0.0001 |
3+ | 12 (66.7) | 270 (68.1) | 35 (87.5) | 219 (90.9) | ||
Mortality, n (%) | 3 (16.7) | 45 (11.4) | 9 (22.5) | 42 (17.4) | 0.060 |
Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | p-Value | ||
LB HER2 + AR− | 1.21 (0.34–4.26) | 0.770 | - | - | |
LB HER2 + AR+ | 0.58 (0.38–0.89) | 0.010 | 4.17 (0.29–59.39) | 0.290 | |
HER2 + AR− | 1.82 (0.84–3.96) | 0.130 | - | - | |
HER2 + AR+ | 1.47 (0.95–2.27) | 0.080 | - | - | |
Age, years | 1.03 (1.01–1.05) | <0.0001 | 1.02 (0.99–1.04) | 0.200 | |
Age ≥ 50 years | 1.50 (0.89–2.53) | 0.130 | - | - | |
Histologic type, CDI VS. others | 0.49 (0.29–0.81) | 0.006 | 0.36 (0.18–0.75) | 0.006 | |
Histologic grade G3 VS. G2 | 4.08 (1.62–10.27) | 0.003 | 2.21 (0.68–7.18) | 0.190 | |
Tumor size, from pT0 to pT4 | 2.49 (1.96–3.17) | <0.0001 | - | - | |
Pathological tumor size | pT0 * | Ref. | - | - | |
pT1 | 1.05 (0.22–5.08) | 0.960 | 1.31 (0.24–7.11) | 0.750 | |
pT2 | 3.99 (0.93–17.07) | 0.060 | 2.51 (0.53–11.87) | 0.240 | |
pT3 | 4.44 (0.76–25.97) | 0.100 | 2.56 (0.34–19.48) | 0.360 | |
pT4 | 23.61 (5.20–107.30) | <0.0001 | 5.25 (0.87–31.47) | 0.070 | |
Pathological lymph node status, from pN0 to pN3 | 2.12 (1.65–2.71) | <0.0001 | - | - | |
Pathological lymph node status | pN0 | Ref. | Ref. | - | - |
pN1 | 2.40 (1.15–5.01) | 0.020 | 1.20 (0.47–3.11) | 0.700 | |
pN2 | 4.13 (1.89–9.03) | <0.0001 | 2.11 (0.49–9.15) | 0.320 | |
pN3 | 10.17 (4.62–22.36) | <0.0001 | 3.17 (0.57–17.69) | 0.190 | |
Lymph node ratio | 8.47 (3.76–19.10) | <0.0001 | - | - | |
Lymph node ratio | ≤0.20 | Ref. | Ref. | - | - |
0.21–0.65 | 2.67 (1.37–5.20) | 0.004 | 1.06 (0.35–3.21) | 0.910 | |
>0.65 | 6.36 (3.02–13.40) | <0.0001 | 1.60 (0.45–5.88) | 0.480 | |
Prognostic stage, from I to IV | 2.89 (2.22–3.76) | <0.0001 | - | - | |
Prognostic stage | I | Ref. | Ref. | - | - |
II | 3.26 (1.38–7.74) | 0.007 | 1.43 (0.47–4.42) | 0.530 | |
III | 8.61 (3.82–19.40) | <0.0001 | 1.96 (0.45–8.52) | 0.370 | |
IV | 25.97 (10.72–62.89) | <0.0001 | 1.79 (0.23–14.14) | 0.580 | |
Metastasis | 7.23 (4.02–12.99) | <0.0001 | - | - | |
Proliferation index, % | 1.02 (1.01–1.03) | 0.002 | 1.02 (0.99–1.04) | 0.150 | |
Proliferation index (Ki-67) ≥14% | - | - | - | - | |
ER expression, % | 0.99 (0.99–1.00) | 0.008 | - | - | |
ER expression ≥10% | 0.59 (0.39–0.91) | 0.020 | 0.17 (0.02–2.42) | 0.190 | |
PR expression, % | 0.99 (0.99–1.00) | 0.070 | - | - | |
PR expression ≥10% | 0.53 (0.32–0.87) | 0.010 | 1.28 (0.47–3.44) | 0.630 | |
AR expression, % | 0.99 (0.98–0.99) | 0.008 | 0.99 (0.98–1.00) | 0.050 | |
AR expression ≥10% | 0.62 (0.32–1.22) | 0.170 | - | - | |
HER2, % | 1.00 (0.99–1.01) | 0.480 | - | - | |
HER2 expression 3 + VS. 2+ | 1.20 (0.71–2.03) | 0.490 | - | - |
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Orrù, S.; Pascariello, E.; Sotgiu, G.; Piras, D.; Saderi, L.; Muroni, M.R.; Carru, C.; Arru, C.; Mocci, C.; Pinna, G.; et al. Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes. Biomedicines 2022, 10, 164. https://doi.org/10.3390/biomedicines10010164
Orrù S, Pascariello E, Sotgiu G, Piras D, Saderi L, Muroni MR, Carru C, Arru C, Mocci C, Pinna G, et al. Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes. Biomedicines. 2022; 10(1):164. https://doi.org/10.3390/biomedicines10010164
Chicago/Turabian StyleOrrù, Sandra, Emanuele Pascariello, Giovanni Sotgiu, Daniela Piras, Laura Saderi, Maria Rosaria Muroni, Ciriaco Carru, Caterina Arru, Cristina Mocci, Giampietro Pinna, and et al. 2022. "Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes" Biomedicines 10, no. 1: 164. https://doi.org/10.3390/biomedicines10010164
APA StyleOrrù, S., Pascariello, E., Sotgiu, G., Piras, D., Saderi, L., Muroni, M. R., Carru, C., Arru, C., Mocci, C., Pinna, G., Barbara, R., Cossu-Rocca, P., & De Miglio, M. R. (2022). Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes. Biomedicines, 10(1), 164. https://doi.org/10.3390/biomedicines10010164