Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | PIK3CA WT (n = 1179) | PIK3CA MUT (n = 693) | p-Value (PIK3CA WT vs. MUT) | PIK3CA MUT (Exon 10, n = 257) | PIK3CA MUT (Exon 20, n = 323) | p-Value (Exon 10 vs. Exon 20 Mutations) |
---|---|---|---|---|---|---|
Age at diagnosis (mean ± SD), range | 50.67 (±11.13); range: 20–83 | 52.77 (±11.55); range: 24–88) | 0.0002 | 53.57 (±11.33); (range: 29–88) | 52.07 (±11.22); (range: 24–85) | 0.110 |
Histologic type | ||||||
Invasive cancer of no special type (NST) (n = 1448) | 903 (86.2%) | 545 (86.1%) | 0.909 | 191 (83.0%) | 267 (89.0%) | 0.423 |
Invasive lobular cancer (ILC) (n = 156) | 96 (9.2%) | 60 (9.5%) | (NST vs. ILC) | 23 (10.0%) | 24 (8.0%) | (NST vs. ILC) |
Other (n = 77) | 49 (4.7%) | 28 (4.4%) | 16 (7.0%) | 9 (3.0%) | ||
ND (n = 191) | ||||||
Primary tumor size (T) | ||||||
T1 (n = 386) | 230 (21.1%) | 156 (24.3%) | 0.005 | 60 (25.0%) | 77 (26.1%) | 0.114 |
T2 (n = 809) | 495 (45.4%) | 314 (48.8%) | (T1–T2 vs. T3–T4) | 109 (45.4%) | 149 (50.5%) | (T1–T2 vs. T3–T4) |
T3 (n = 125) | 94 (8.6%) | 31 (4.8%) | 13 (5.4%) | 11 (3.7%) | ||
T4 (n = 414) | 272 (24.9%) | 142 (22.1%) | 58 (24.2%) | 58 (19.7%) | ||
Other/ND (n = 138) | ||||||
Lymph node involvement (N) | ||||||
N0 (n = 485) | 302 (27.9%) | 183 (29.1%) | 0.780 | 63 (27.0%) | 91 (31.4%) | 0.713 |
N1 (n = 588) | 371 (34.3%) | 217 (34.5%) | 86 (36.9%) | 97 (33.4%) | ||
N2 (n = 323) | 212 (19.6%) | 111 (17.6%) | 42 (18.0%) | 49 (16.9%) | ||
N3 (n = 314) | 196 (18.1%) | 118 (18.8%) | 42 (18.0%) | 53 (18.3%) | ||
ND (n = 162) | ||||||
Distant metastasis (M) | ||||||
M0 (n = 1240) | 769 (79.5%) | 471 (81.9%) | 0.253 | 174 (81.7%) | 215 (82.4%) | 0.847 |
M1 (n = 302) | 198 (20.5%) | 104 (18.1%) | 39 (18.3%) | 46 (17.6%) | ||
ND (n = 330) | ||||||
Bilateral/unilateral disease | ||||||
Unilateral BC (n = 1785) | 1118 (94.8%) | 667 (96.2%) | 0.194 | 247 (96.1%) | 307 (95.3%) | 0.606 |
Bilateral BC (n = 87) | 61 (5.2%) | 26 (3.8%) | 10 (3.9%) | 15 (4.7%) | ||
Stage | ||||||
I (n = 184) | 115 (10.6%) | 69 (11.0%) | 0.536 | 22 (9.6%) | 38 (13.1%) | 0.557 |
II (n = 576) | 353 (32.7%) | 223 (35.6%) | 80 (34.8%) | 104 (36.0%) | ||
III (n = 619) | 396 (36.6%) | 223 (35.6%) | 86 (37.4%) | 97 (33.6%) | ||
IV (n = 329) | 217 (20.1%) | 112 (17.9%) | 42 (18.3%) | 50 (17.3%) | ||
ND (n = 164) | ||||||
Grade | ||||||
G1 (n = 99) | 50 (7.6%) | 49 (12.4%) | 0.005 | 14 (9.7%) | 26 (14.0%) | 0.673 |
G2 (n = 726) | 452 (68.4%) | 274 (69.5%) | 103 (71.5%) | 124 (66.7%) | ||
G3 (n = 230) | 159 (24.1%) | 71 (18.0%) | 27 (18.8%) | 36 (19.4%) | ||
ND (n = 817) | ||||||
PR status | ||||||
Negative (n = 485) | 335 (28.9%) | 150 (22.2%) | 0.002 | 59 (23.5%) | 69 (21.7%) | 0.608 |
Positive (n = 1350) | 823 (71.1%) | 527 (77.8%) | 192 (76.5%) | 249 (78.3%) | ||
ND (n = 37) | ||||||
Ki67 | ||||||
Low (<20%) (n = 563) | 319 (32.8%) | 244 (42.4%) | 0.0001 | 79 (36.7%) | 126 (47.2%) | 0.021 |
High (≥20%) (n = 984) | 653 (67.2%) | 331 (57.6%) | 136 (63.3%) | 141 (52.8%) | ||
ND (n = 325) | ||||||
Number of metastatic sites | ||||||
N = 1 (n = 531) | 302 (32.9%) | 229 (43.2%) | 0.0001 | 91 (44.8%) | 100 (42.6%) | 0.633 |
N > 1 (n = 917) | 616 (67.1%) | 301 (56.8%) | 112 (55.2%) | 135 (57.4%) | ||
ND (n = 424) | ||||||
Distant metastases | ||||||
Bones | ||||||
Yes (n = 874) | 548 (59.5%) | 326 (61.2%) | 0.389 | 115 (56.7%) | 152 (64.1%) | 0.110 |
No (n = 580) | 373 (40.5%) | 207 (38.8%) | 88 (43.3%) | 85 (35.9%) | ||
Brain | ||||||
Yes (n = 46) | 34 (3.7%) | 12 (2.3%) | 0.133 | 5 (2.5%) | 5 (2.1%) | 0.810 |
No (n = 1405) | 886 (96.3%) | 519 (97.7%) | 198 (97.5%) | 231 (97.9%) | ||
Liver | ||||||
Yes (n = 453) | 291(31.6%) | 162 (30.4%) | 0.240 | 67 (33.0%) | 71 (30.0%) | 0.493 |
No (n = 1000) | 629 (68.4%) | 371 (69.6%) | 136 (67.0%) | 166 (70.0%) | ||
Lung | ||||||
Yes (n = 457) | 295 (31.0%) | 162 (29.3%) | 0.474 | 55 (26.7%) | 81 (32.3%) | 0.218 |
No (n = 1046) | 656 (69.0%) | 390 (70.7%) | 151 (73.3%) | 170 (67.7%) | ||
Lymph nodes | ||||||
Yes (n = 579) | 383 (41.5%) | 196 (36.8%) | 0.084 | 83 (40.7%) | 80 (33.9%) | 0.142 |
No (n = 877) | 541 (58.5%) | 336 (63.2%) | 121 (59.3%) | 156 (66.1%) | ||
Peritoneum | ||||||
Yes (n = 38) | 28 (3.0%) | 10 (1.9%) | 0.181 | 4 (2.0%) | 5 (2.1%) | 0.918 |
No (n = 1414) | 892 (97.0%) | 522 (98.1%) | 199 (98.0%) | 232 (97.9%) | ||
Pleura | ||||||
Yes (n = 160) | 100 (10.9%) | 60 (11.3%) | 0.801 | 18 (8.9%) | 30 (12.7%) | 0.199 |
No (n = 1291) | 820 (89.1%) | 471 (88.7%) | 185 (91.1%) | 206 (87.3%) | ||
Skin | ||||||
Yes (n = 118) | 84 (9.1%) | 34 (6.4%) | 0.069 | 10 (4.9%) | 18 (7.6%) | 0.249 |
No (n = 1335) | 838 (90.9%) | 497 (93.6%) | 193 (95.1%) | 218 (92.4%) | ||
Soft tissues | ||||||
Yes (n = 114) | 82 (8.9%) | 32 (6.0%) | 0.049 | 13 (6.4%) | 16 (6.8%) | 0.875 |
No (n = 1336) | 837 (91.1%) | 499 (94.0%) | 190 (93.6%) | 220 (93.2%) |
Federal District | PIK3CA WT (n = 1179) | PIK3CA MUT (n = 693) | p-Value (PIK3CA WT vs. MUT) | PIK3CA MUT (Exon 10, n = 257) | PIK3CA MUT (Exon 20, n = 323) | p-Value (Exon 10 vs. Exon 20 Mutations) |
---|---|---|---|---|---|---|
Northwestern (n = 713) | 451 (63.3%) | 262 (36.7%) | 0.800 | 103 (46.0%) | 121 (54.0%) | 0.400 |
Southern (n = 217) | 133 (61.3%) | 84 (38.7%) | 29 (42.0%) | 40 (58.0%) | ||
Central (n = 185) | 110 (59.5%) | 75 (40.5%) | 33 (52.4%) | 30 (47.6%) | ||
North Caucasian (n = 175) | 116 (66.3%) | 59 (33.7%) | 27 (49.1%) | 28 (50.9%) | ||
Volga (n = 129) | 81 (62.8%) | 48 (37.2%) | 14 (33.3%) | 28 (66.7%) | ||
Khanty-Mansi (n = 113) | 78 (69.0%) | 35 (31.0%) | 9 (32.1%) | 19 (67.9%) | ||
Siberian (n = 109) | 67 (61.5%) | 42 (38.5%) | 17 (51.5%) | 16 (48.4%) | ||
Urals (n = 88) | 54 (61.4%) | 34 (38.6%) | 11 (45.8%) | 13 (54.2%) | ||
Far Eastern (n = 88) | 52 (59.1%) | 36 (40.9%) | 8 (29.6%) | 19 (70.4%) | ||
Yamalo-Nenets (n = 13) | 6 (46.2%) | 7 (53.8%) | 2 (33.3%) | 4 (66.7%) | ||
ND (n = 42) |
Parameter | Univariable | Multivariable | ||
---|---|---|---|---|
Hazard Ratio [95% CI] | p-Value | Hazard Ratio [95% CI] | p-Value | |
Age (<60 vs. ≥60 years) (n = 415) | 1.473 [1.151–1.886] (≥60) | 0.0006 | 1.482 [1.178–1.866] | 0.0008 |
Grade (G1–2 vs. G3) (n = 216) | 1.126 [0.818–1.550] (G3) | 0.384 | ||
Ki67 (<20% vs. ≥20%) (n = 342) | 1.075 [0.860–1.344] (≥20%) | 0.529 | ||
Stage (I–III) (n = 431) | 1.401 [1.213–1.619] * | <0.0001 | ||
Tumor size (T1–2 vs. T3–4) (n = 412) | 1.378 [1.068–1.777] (T3–4) | 0.0063 | 1.301 [1.024–1.653] | 0.031 |
Nodal involvement (N0 vs. N1–3) (n = 414) | 0.687 [0.562–0.838] (N0) | 0.0005 | 0.722 [0.577–0.903] | 0.004 |
PR status (positive vs. negative) (n = 418) | 1.020 [0.822–1.266] (PR-) | 0.856 | ||
PIK3CA (wt vs. mut) (n = 431) | 1.055 [0.867–1.283] (mut) | 0.592 |
Type of Adjuvant Therapy | Primary Resistance | Secondary Resistance | Sensitivity | p-Value |
---|---|---|---|---|
Tamoxifen (n = 331) | 66/163 (40.5%) | 28/103 (27.2%) | 28/65 (43.1%) | 0.046 |
Aromatase inhibitors (n = 82) | 19/42 (45.2%) | 11/28 (39.3%) | 4/12 (33.3%) | 0.730 |
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Sokolova, T.N.; Yanus, G.A.; Aleksakhina, S.N.; Belysheva, Y.V.; Chernyakova, A.P.; Zharnakova, Y.S.; Nikitina, A.S.; Stebneva, T.M.; Martianov, A.S.; Goryainova, A.Y.; et al. Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients. Cancers 2025, 17, 1833. https://doi.org/10.3390/cancers17111833
Sokolova TN, Yanus GA, Aleksakhina SN, Belysheva YV, Chernyakova AP, Zharnakova YS, Nikitina AS, Stebneva TM, Martianov AS, Goryainova AY, et al. Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients. Cancers. 2025; 17(11):1833. https://doi.org/10.3390/cancers17111833
Chicago/Turabian StyleSokolova, Tatyana N., Grigory A. Yanus, Svetlana N. Aleksakhina, Yana V. Belysheva, Aleksandra P. Chernyakova, Yulia S. Zharnakova, Alisa S. Nikitina, Tatyana M. Stebneva, Aleksandr S. Martianov, Alla Yu. Goryainova, and et al. 2025. "Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients" Cancers 17, no. 11: 1833. https://doi.org/10.3390/cancers17111833
APA StyleSokolova, T. N., Yanus, G. A., Aleksakhina, S. N., Belysheva, Y. V., Chernyakova, A. P., Zharnakova, Y. S., Nikitina, A. S., Stebneva, T. M., Martianov, A. S., Goryainova, A. Y., Gluzman, M. I., Orlova, R. V., Stukan’, A. I., Zyuzyukina, A. V., Zukov, R. A., Korzun, P. R., Binnatova, J. O., Abuzova, A. S., Murunova, Y. N., ... Imyanitov, E. N. (2025). Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients. Cancers, 17(11), 1833. https://doi.org/10.3390/cancers17111833