Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Data Collection
2.3. Assessment of CBR Expression
2.4. Survival Outcome
2.5. Statistical Analyses
3. Results
3.1. Study Population
3.2. CBR Expression and Breast Cancer Prognostic Factors
3.3. CBR Expression and Breast Cancer Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics * | All (n = 522) | CBR1 (n = 489) | CBR2 in Cytoplasm (n = 475) | CBR2 in Nuclear (n = 475) | |||
---|---|---|---|---|---|---|---|
Low * (n = 235) | High * (n = 254) | Low * (n = 211) | High * (n = 264) | Low * (n = 206) | High * (n = 269) | ||
Age (years) | |||||||
Mean ± SD | 61.2 ± 12.6 | 62.3 ± 12.6 | 60.4 ± 12.99 | 62.9 ± 12.6 | 60.0 ± 12.8 | 61.9 ± 13.3 | 60.8 ± 12.3 |
Median [range] | 61.0 [24.0–92.0] | 63.0 [32.0–91.0] | 61.0 [24.0–92.0] | 64.0 [24.0–91.0] | 61.0 [25.0–92.0] | 63.0 [24.0–91.0] | 61.0 [25.0–92.0] |
Postmenopausal | 399 (76.4%) | 186 (79.2%) | 189 (74.4%) | 168 (79.6%) | 194 (73.5%) | 155 (75.2%) | 207 (77.0%) |
Familial history of breast cancer (yes) | 245 (46.9%) | 110 (46.8%) | 123 (48.4%) | 97 (45.9%) | 125 (47.4%) | 96 (46.6%) | 126 (46.8%) |
Ever smokers | 254 (48.7%) | 119 (50.6%) | 118 (46.5%) | 112 (53.1%) | 120 (45.5%) | 95 (46.1%) | 137 (50.9%) |
Alcohol consumption (yes) | 337 (64.6%) | 147 (62.6%) | 168 (66.1%) | 128 (60.7%) | 179 (67.8%) | 131 (63.6%) | 176 (65.4%) |
Body mass index (kg/m2) | |||||||
Mean ± SD | 26.3 ± 5.2 | 25.8 ± 5.2 | 26.6 ± 5.3 | 26.1 ± 5.0 | 26.4 ± 5.5 | 26.3 ± 5.2 | 26.2 ± 5.3 |
Median [range] | 25.5 [15.2–45.9] | 24.6 [16.3–44.1] | 25.6 [15.2–45.9] | 25.0 [17.7–44.1] | 25.5 [15.2–45.9] | 25.6 [16.3–44.6] | 25.3 [15.2–45.9] |
Personal history of breast cancer (yes) | 63 (12.1%) | 25 (10.6%) | 32 (12.6%) | 26 (12.3%) | 29 (11.0%) | 23 (11.2%) | 32 (11.9%) |
Histologic type | |||||||
Ductal, invasive | 451 (86.4%) | 204 (86.8%) | 220 (86.6%) | 180 (85.3%) | 235 (89.0%) | 189 (91.8%) | 226 (84.0%) |
Lobular, invasive | 56 (10.7%) | 27 (11.5%) | 24 (9.5%) | 24 (11.4%) | 23 (8.7%) | 12 (5.8%) | 35 (13.0%) |
Mixed ductal and lobular, invasive | 15 (2.9%) | 4 (1.7%) | 10 (3.9%) | 7 (3.3%) | 6 (2.3%) | 5 (2.4%) | 8 (3.0%) |
Tumour grade | |||||||
1 | 86 (16.5%) | 39 (16.6%) | 38 (15.0%) | 30 (14.2%) | 42 (18.9%) | 23 (11.2%) | 49 (18.2%) |
2 | 258 (49.4%) | 112 (47.7%) | 130 (51.2%) | 119 (56.4%) | 116 (43.9%) | 90 (43.7%) | 145 (53.9%) |
3 | 178 (34.1%) | 84 (35.7%) | 86 (33.9%) | 62 (29.4%) | 106 (40.2%) | 93 (45.2%) | 75 (27.9%) |
Tumour size | |||||||
≤2 cm | 293 (56.1%) | 130 (55.3%) | 140 (55.1%) | 114 (54.0%) | 148 (56.1%) | 110 (53.4%) | 152 (56.5%) |
>2 and ≤5 cm | 209 (40.0%) | 101 (43.0%) | 99 (39.0%) | 89 (42.2%) | 106 (40.2%) | 93 (45.2%) | 102 (37.9%) |
>5 cm | 20 (3.8%) | 4 (1.7%) | 15 (5.9%) | 8 (3.8%) | 10 (3.8%) | 3 (1.5%) | 15 (5.6%) |
Positive lymph nodes | |||||||
0 | 312 (59.8%) | 153 (65.1%) | 137 (53.9%) | 135 (64.0%) | 146 (55.3%) | 125 (60.7%) | 156 (58.0%) |
1–3 | 146 (28.0%) | 60 (25.5%) | 78 (30.7%) | 55 (26.1%) | 80 (30.3%) | 59 (28.6%) | 76 (28.3%) |
4–9 | 42 (8.0%) | 17 (7.2%) | 22 (8.7%) | 14 (6.6%) | 26 (9.8%) | 18 (8.7%) | 22 (8.2%) |
≥10 | 22 (4.2%) | 5 (2.1%) | 17 (6.7%) | 7 (3.3%) | 12 (4.6%) | 4 (1.9%) | 15 (5.6%) |
Disease stage | |||||||
I | 203 (38.9%) | 96 (40.9%) | 91 (35.8%) | 84 (39.8%) | 97 (36.7%) | 76 (36.9%) | 105 (39.0%) |
II | 241 (46.2%) | 110 (46.8%) | 119 (46.9%) | 101 (47.9%) | 122 (46.2%) | 104 (50.5%) | 119 (44.2%) |
III | 71 (13.6%) | 28 (11.9%) | 38 (18.0%) | 25 (11.9%) | 39 (14.8%) | 24 (11.7%) | 40 (14.9%) |
IV | 7 (1.3%) | 1 (0.4%) | 6 (2.4%) | 1 (0.5%) | 6 (2.3%) | 2 (1.0%) | 5 (1.9%) |
ER status | |||||||
Negative | 64 (12.3%) | 29 (12.3%) | 30 (11.8%) | 35 (16.6%) | 25 (9.5%) | 37 (18.0%) | 23 (8.6%) |
Positive | 458 (87.7%) | 206 (87.7%) | 224 (88.2%) | 176 (83.4%) | 239 (90.5%) | 169 (82.0%) | 246 (91.5%) |
PR status | |||||||
Negative | 108 (20.7%) | 46 (19.6%) | 52 (20.5%) | 51 (24.1%) | 47 (17.8%) | 53 (25.7%) | 45 (16.7%) |
Positive | 414 (79.3%) | 189 (80.4%) | 202 (79.5%) | 160 (75.8%) | 217 (82.2%) | 153 (74.3%) | 224 (83.3%) |
HER2 status | |||||||
Negative | 455 (87.2%) | 215 (91.5%) | 210 (82.7%) | 191 (90.5%) | 222 (84.1%) | 180 (87.4%) | 233 (86.6%) |
Positive | 67 (12.8%) | 20 (8.5%) | 44 (17.3%) | 20 (9.5%) | 42 (15.9%) | 26 (12.6%) | 36 (13.4%) |
Surgery | |||||||
Partial | 384 (73.6%) | 173 (73.6%) | 187 (73.6%) | 156 (73.9%) | 195 (73.9%) | 154 (74.8%) | 197 (73.2%) |
Total | 138 (26.4%) | 62 (26.4%) | 67 (26.4%) | 55 (26.1%) | 69 (26.1%) | 52 (25.2%) | 72 (26.8%) |
Chemotherapy prior to surgery (yes) | 6 (1.2%) | 1 (0.4%) | 2 (0.8%) | 1 (0.5%) | 2 (0.8%) | 1 (0.5%) | 2 (0.7%) |
Hormone therapy prior to surgery (yes) | 6 (1.2%) | 3 (1.3%) | 3 (1.2%) | 4 (1.9%) | 2 (0.8%) | 1 (0.5%) | 5 (1.9%) |
Chemotherapy after surgery (yes) | 263 (50.4%) | 108 (46.0%) | 138 (54.3%) | 94 (44.6%) | 146 (55.3%) | 106 (51.5%) | 134 (49.8%) |
Radiotherapy after surgery (yes) | 414 (79.3%) | 184 (78.3%) | 204 (80.3%) | 164 (77.7%) | 212 (80.3%) | 163 (79.1%) | 213 (79.2%) |
Hormone therapy after surgery (yes) | 433 (83.0%) | 189 (80.4%) | 217 (85.4%) | 164 (77.7%) | 229 (86.7%) | 157 (76.2%) | 236 (87.7%) |
Trastuzumab after surgery (yes) | 59 (11.3%) | 20 (8.4%) | 36 (14.2%) | 15 (7.1%) | 39 (14.8%) | 23 (11.2%) | 31 (11.5%) |
Follow-up (months) | |||||||
Mean ± SD | 84.7 ± 20.7 | 83.0 ± 21.7 | 86.3 ± 19.6 | 84.6 ± 20.8 | 84.4 ± 21.2 | 84.7 ± 21.2 | 84.7 ± 20.9 |
Median [range] | 92.0 [7.0–114.0] | 91.0 [7.0–112.0] | 93.0 [11.0–114] | 93.0 [7.0–112.0] | 92.0 [7.0–114.0] | 92.0 [14.0–112.0] | 92.0 [7.0–114.0] |
Survival outcomes | |||||||
Deaths | 86 (16.5%) | 41 (17.5%) | 40 (15.8%) | 39 (18.5%) | 43 (16.3%) | 42 (20.4%) | 40 (14.9%) |
Recurrences § | 74 (14.2%) | 31 (13.2%) | 36 (14.2%) | 24 (11.4%) | 44 (16.7%) | 31 (15.1%) | 37 (13.8%) |
Events † | 143 (27.4%) | 65 (27.7%) | 69 (27.2%) | 60 (28.4%) | 74 (28.0%) | 65 (31.6%) | 69 (25.7%) |
CBR1 (n = 489) | CBR2 in Cytoplasm (n = 475) | CBR2 in Nuclear (n = 475) | |||||||
---|---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusted * | Fully Adjusted § | Unadjusted | Adjusted * | Fully Adjusted § | Unadjusted | Adjusted * | Fully Adjusted § | |
Histologic type | |||||||||
rs | −0.009 | 0.004 | 0.006 | −0.022 | −0.004 | −0.002 | 0.144 | 0.148 | 0.147 |
p-value | 0.8451 | 0.9316 | 0.9045 | 0.6399 | 0.9301 | 0.9602 | 0.0016 | 0.0013 | 0.0014 |
Tumour size | |||||||||
rs | 0.017 | 0.025 | 0.011 | 0.030 | 0.046 | 0.032 | 0.013 | 0.023 | 0.030 |
p-value | 0.7148 | 0.5795 | 0.8074 | 0.5158 | 0.3207 | 0.4843 | 0.7721 | 0.6163 | 0.5163 |
Positive lymph nodes | |||||||||
rs | 0.116 | 0.110 | 0.107 | 0.072 | 0.063 | 0.060 | 0.060 | 0.063 | 0.064 |
p-value | 0.0103 | 0.0155 | 0.0194 | 0.1180 | 0.1767 | 0.1978 | 0.2158 | 0.1770 | 0.1676 |
Tumour grade | |||||||||
rs | 0.003 | −0.006 | −0.014 | 0.052 | 0.043 | 0.036 | −0.170 | −0.171 | −0.170 |
p-value | 0.9451 | 0.9008 | 0.7632 | 0.2572 | 0.3577 | 0.4420 | 0.0002 | 0.0002 | 0.0002 |
Disease stage | |||||||||
rs | 0.073 | 0.077 | 0.067 | 0.050 | 0.055 | 0.046 | 0.020 | 0.025 | 0.030 |
p-value | 0.1083 | 0.0898 | 0.1444 | 0.2812 | 0.2310 | 0.3242 | 0.6603 | 0.5929 | 0.5227 |
ER status | |||||||||
rs | 0.028 | 0.021 | 0.022 | 0.096 | 0.089 | 0.090 | 0.172 | 0.173 | 0.173 |
p-value | 0.5448 | 0.6405 | 0.6336 | 0.0358 | 0.0546 | 0.0528 | 0.0002 | 0.0002 | 0.0002 |
PR status | |||||||||
rs | −0.023 | −0.031 | −0.029 | 0.033 | 0.025 | 0.026 | 0.119 | 0.121 | 0.121 |
p-value | 0.6081 | 0.5027 | 0.5287 | 0.4704 | 0.5963 | 0.5755 | 0.0096 | 0.0084 | 0.0087 |
HER2 status | |||||||||
rs | 0.176 | 0.168 | 0.165 | 0.086 | 0.080 | 0.076 | 0.031 | 0.032 | 0.034 |
p-value | <0.0001 | 0.0002 | 0.0003 | 0.0623 | 0.0848 | 0.0990 | 0.4989 | 0.4915 | 0.4695 |
CBR | Events/Total | Crude HR (95% CI) | p-Value | Adjusted § HR (95% CI) | p-Value | Fully Adjusted † HR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|
Overall survival | |||||||
CBR1 | 81/489 | 0.98 [0.88–1.09] | 0.70 | 1.01 [0.90–1.13] | 0.86 | 1.02 [0.91–1.14] | 0.74 |
CBR2 cytoplasmic | 82/475 | 0.95 [0.82–1.09] | 0.46 | 1.03 [0.88–1.20] | 0.74 | 1.02 [0.87–1.19] | 0.84 |
CBR2 nuclear | 82/475 | 0.99 [0.90–1.09] | 0.76 | 1.01 [0.90–1.11] | 0.91 | 1.01 [0.92–1.12] | 0.81 |
Recurrence-free survival | |||||||
CBR1 | 67/489 | 1.04 [0.93–1.17] | 0.49 | 1.02 [0.92–1.14] | 0.71 | 1.04 [0.93–1.18] | 0.49 |
CBR2 cytoplasmic | 68/475 | 0.96 [0.83–1.11] | 0.59 | 1.13 [0.97–1.33] | 0.13 | 1.09 [0.93–1.28] | 0.28 |
CBR2 nuclear | 68/475 | 0.99 [0.90–1.09] | 0.77 | 1.01 [0.90–1.13] | 0.86 | 1.01 [0.90–1.13] | 0.86 |
Event-free survival | |||||||
CBR1 | 134/489 | 1.00 [0.92–1.09] | 0.97 | 1.01 [0.93–1.10] | 0.75 | 1.01 [0.93–1.10] | 0.81 |
CBR2 cytoplasmic | 134/475 | 0.98 [0.87–1.10] | 0.71 | 1.01 [0.90–1.14] | 0.81 | 1.01 [0.90–1.14] | 0.82 |
CBR2 nuclear | 134/475 | 0.98 [0.91–1.06] | 0.69 | 1.00 [1.00–1.00] | 0.22 | 1.00 [1.00–1.00] | 0.25 |
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Morin-Buote, J.; Ennour-Idrissi, K.; Poirier, É.; Lemieux, J.; Furrer, D.; Burguin, A.; Durocher, F.; Diorio, C. Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients. J. Pers. Med. 2021, 11, 852. https://doi.org/10.3390/jpm11090852
Morin-Buote J, Ennour-Idrissi K, Poirier É, Lemieux J, Furrer D, Burguin A, Durocher F, Diorio C. Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients. Journal of Personalized Medicine. 2021; 11(9):852. https://doi.org/10.3390/jpm11090852
Chicago/Turabian StyleMorin-Buote, Jessica, Kaoutar Ennour-Idrissi, Éric Poirier, Julie Lemieux, Daniela Furrer, Anna Burguin, Francine Durocher, and Caroline Diorio. 2021. "Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients" Journal of Personalized Medicine 11, no. 9: 852. https://doi.org/10.3390/jpm11090852