The Vitamin D Receptor as a Prognostic Marker in Breast Cancer—A Cohort Study
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Population
2.2. Clinical Information and Histopathological Analysis
2.3. Tissue Microarray
2.4. Microscopy Assessment
2.5. Endpoint Retrieval
2.6. Statistical Methods
3. Results
3.1. Patient Characteristics
3.2. Tumor Characteristics and Adjuvant Treatment
3.3. VDR Levels and Prognosis
3.4. Effect Modification between VDRnum and Clinicopathological Factors
4. Discussion
4.1. Associations of VDR with Different Types of Breast Cancer
4.2. Using VDR as a Prognostic Factor and Vitamin D Supplements in Breast Cancer Treatment
4.3. Generalizability of the Results
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Variable Included in Cox Model | Missing Number Out of 1018 | Variable Included in MI Model |
---|---|---|
VDRnum | 140 | VDRnum |
BC event/death | 0 | BC event/death |
Follow-up time | 0 | Log of follow-up time |
Time between surgery and staining | 0 | Time between surgery and staining |
Age at inclusion | 0 | Age at inclusion |
303 | Age at menopause | |
0 | Parity | |
BMI | 28 | BMI |
26 | Height | |
26 | Weight | |
38 | Waist circumference | |
160 | Breast volume | |
1 | Use of oral contraceptives | |
3 | Menopausal hormone therapy | |
7 | Vitamin D supplementation | |
2 | Smoking | |
3 | Alcohol | |
0 | Detection mode | |
0 | Month of surgery | |
Tumor size | 0 | Tumor size |
Lymph node involvement | 2 | Lymph node involvement |
Histologic grade | 1 | Histologic grade |
0 | Histologic type | |
ER | 1 | ER |
1 | PgR | |
63 | HER2 | |
7 | Triple-negative tumor | |
Radiation therapy | 0 | Radiation therapy |
Chemotherapy | 0 | Chemotherapy |
Herceptin | 0 | Herceptin |
Aromatase inhibitors | 0 | Aromatase inhibitors |
Tamoxifen | 0 | Tamoxifen |
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Eligible Cases | All n = 1018 | ||||
---|---|---|---|---|---|
Tumor in Tissue Microarray n (%) | Yes 984 (96.7) | No 34 (3.3) | |||
VDR Assessable n (%) | Yes 878 (89.2) | No 106 (10.8) | |||
Nuclear Membrane VDR n (%) | Negative 663 (75.6) | Positive 215 (24.5) | |||
Factor | n (%) | n (%) | n (%) | n (%) | n (%) |
Invasive tumor size | |||||
1–20 mm | 743 (73.0) | 471 (71.0) | 166 (77.2) | 76 (71.7) | 30 (88.2) |
>20 mm * | 275 (27.0) | 192 (29.0) | 49 (22.8) | 30 (28.3) | 4 (11.8) |
Lymph node status | |||||
Negative | 627 (61.6) | 390 (58.8) | 135 (62.8) | 79 (74.5) | 23 (67.6) |
Positive | 389 (38.2) | 271 (40.9) | 80 (37.2) | 27 (25.5) | 11 (32.4) |
Nottingham grade | |||||
I | 258 (25.3) | 123 (18.6) | 87 (40.5) | 38 (35.8) | 10 (29.4) |
II | 502 (49.3) | 326 (49.2) | 104 (48.4) | 55 (51.9) | 17 (50.0) |
III | 257 (25.2) | 214 (32.3) | 24 (11.2) | 12 (11.3) | 7 (20.6) |
Histological type | |||||
Ductal | 824 (80.9) | 554 (83.6) | 176 (81.9) | 67 (63.2) | 27 (79.4) |
Lobular | 116 (11.4) | 60 (9.0) | 24 (11.2) | 28 (26.4) | 4 (11.8) |
Other/mixed | 78 (7.7) | 49 (7.4) | 15 (7.0) | 11 (10.4) | 3 (8.8) |
ER status | |||||
Pos (>10%) | 894 (87.8) | 555 (83.7) | 214 (99.5) | 97 (91.5) | 28 (82.4) |
PgR status | |||||
Pos (>10%) | 723 (71.0) | 441 (66.5) | 179 (83.3) | 79 (74.5) | 24 (70.6) |
HER2 | |||||
Amplified | 110 (11.5) | 87 (13.5) | 10 (4.7) | 7 (9.0) | 6 (31.6) |
Unknown | 63 | 18 | 2 | 28 | 15 |
Triple-negative | |||||
Yes | 74 (7.3) | 68 (10.3) | 0 (0) | 5 (4.8) | 1 (3.2) |
Unknown | 7 | 2 | 0 | 2 | 3 |
Treatment | |||||
Final type of operation | |||||
Mastectomy | 410 (40.3) | 271 (40.9) | 85 (39.5) | 40 (37.7) | 14 (41.2) |
Chemotherapy | 258 (25.3) | 193 (29.1) | 41 (19.1) | 15 (14.2) | 9 (26.5) |
Radiotherapy | 644 (63.4) | 418 (63.0) | 139 (64.7) | 68 (64.2) | 19 (55.9) |
Herceptin | 73 (7.2) | 54 (8.1) | 10 (4.7) | 4 (3.8) | 5 (14.7) |
Endocrine therapy ** | |||||
Tamoxifen | 572 (64.0) | 382 (68.2) | 119 (55.6) | 58 (59.8) | 13 (46.4) |
Aromatase inhibitors | 371 (41.5) | 249 (44.9) | 80 (37.4) | 32 (33.0) | 10 (35.7) |
Event | |||||
Any breast cancer event | 195 (19.2) | 145 (21.9) | 28 (13.0) | 15 (14.2) | 7 (20.6) |
Death | 188 (18.5) | 144 (21.7) | 23 (10.7) | 15 (14.2) | 6 (17.6) |
Eligible Cases | All n = 1018 | ||||
---|---|---|---|---|---|
Tumor in Tissue Microarray n (%) | Yes 984 (96.7) | No 34 (3.3) | |||
VDR Assessable n (%) | Yes 878 (89.2) | No 106 (10.8) | |||
Nuclear Membrane VDR n (%) | Negative 663 (75.6) | Positive 215 (24.5) | |||
Factor | n (%) | n (%) | n (%) | n (%) | n (%) |
Age at diagnosis | |||||
≥50 | 816 (80.2) | 535 (80.7) | 168 (78.1) | 89 (84.0) | 24 (70.6) |
BMI at inclusion | |||||
≥25 | 503 (50.8) | 336 (51.9) | 100 (49.0) | 49 (46.7) | 18 (54.5) |
Unknown | 28 | 15 | 11 | 1 | 1 |
Waist circumference | |||||
≥80 cm | 731 (74.6) | 490 (76.1) | 143 (70.8) | 73 (72.3) | 25 (75.8) |
Unknown | 38 | 19 | 13 | 5 | 1 |
Total breast volume | |||||
≥850 mL | 492 (57.3) | 335 (58.9) | 87 (50.0) | 54 (62.1) | 16 (57.1) |
Unknown | 160 | 94 | 41 | 19 | 6 |
Parity | |||||
Parous | 896 (88.0) | 576 (86.9) | 196 (91.2) | 93 (87.7) | 31 (91.2) |
Oral contraceptives | |||||
Ever | 722 (71.0) | 467 (70.4) | 151 (70.6) | 77 (72.6) | 27 (79.4) |
Menopausal hormone therapy | |||||
Ever | 446 (43.9) | 281 (42.4) | 96 (45.1) | 57 (53.8) | 49 (35.3) |
Alcohol abstainer | |||||
Yes | 106 (10.4) | 72 (10.9) | 23 (10.7) | 11 (10.4) | 0 (0) |
Smoking currently | |||||
Yes | 206 (20.2) | 130 (19.6) | 41 (19.1) | 31 (29.2) | 4 (11.8) |
Vitamin D supplements | |||||
Yes | 103 (10.2) | 71 (10.8) | 16 (7.5) | 10 (9.4) | 6 (17.6) |
Unknown | 7 | 6 | 1 | 0 | 0 |
Season of operation | |||||
Winter (January–March) | 251 (24.8) | 160 (24.1) | 58 (27.0) | 28 (26.4) | 5 (14.7) |
Spring (April–June) | 303 (29.8) | 193 (29.1) | 69 (32.1) | 33 (31.1) | 8 (23.5) |
Summer (July–September) | 177 (17.0) | 111 (16.7) | 38 (17.7) | 20 (18.9) | 8 (23.5) |
Fall (October–December) | 287 (28.4) | 199 (30.0) | 50 (23.3) | 25 (23.5) | 13 (38.2) |
Detection mode (45–74 years) | |||||
Clinical | 290 (33.8) | 208 (37.8) | 52 (28.0) | 21 (22.1) | 9 (32.1) |
Screening | 569 (66.2) | 342 (62.2) | 134 (72.0) | 74 (77.9) | 19 (67.9) |
Breast Cancer Free Interval | |||||||
---|---|---|---|---|---|---|---|
Nuclear Membrane VDR Level | Included in Analyses | Total n | Events n | HR 1 (CI 95%) | HR 2 (CI 95%) | HR 3 (CI 95%) | HR 4 (CI 95%) |
Negative | Complete case * | 663 | 145 | ref | ref | ref | ref |
Positive | 215 | 28 | 0.61 (0.40–0.91) | 0.71 (0.46–1.07) | 0.72 (0.48–1.10) | 0.70 (0.46–1.07) | |
Negative | All included ** | 730 | 155 | ref | ref | ref | ref |
Positive | 288 | 40 | 0.64 (0.44–0.95) | 0.74 (0.49–1.10) | 0.75 (0.50–1.12) | 0.71 (0.47–1.06) | |
Overall Survival | |||||||
Negative | Complete case * | 663 | 144 | ref | ref | ref | ref |
Positive | 215 | 23 | 0.51 (0.33–0.79) | 0.63 (0.40–0.99) | 0.69 (0.42–1.06) | 0.67 (0.42–1.08) | |
Negative | All included ** | 764 | 161 | ref | ref | ref | ref |
Positive | 254 | 27 | 0.52 (0.34–0.78) | 0.62 (0.40–0.96) | 0.64 (0.41–0.99) | 0.65 (0.42–1.00) |
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Huss, L.; Gulz-Haake, I.; Nilsson, E.; Tryggvadottir, H.; Nilsson, L.; Nodin, B.; Jirström, K.; Isaksson, K.; Jernström, H. The Vitamin D Receptor as a Prognostic Marker in Breast Cancer—A Cohort Study. Nutrients 2024, 16, 931. https://doi.org/10.3390/nu16070931
Huss L, Gulz-Haake I, Nilsson E, Tryggvadottir H, Nilsson L, Nodin B, Jirström K, Isaksson K, Jernström H. The Vitamin D Receptor as a Prognostic Marker in Breast Cancer—A Cohort Study. Nutrients. 2024; 16(7):931. https://doi.org/10.3390/nu16070931
Chicago/Turabian StyleHuss, Linnea, Igis Gulz-Haake, Emma Nilsson, Helga Tryggvadottir, Linn Nilsson, Björn Nodin, Karin Jirström, Karolin Isaksson, and Helena Jernström. 2024. "The Vitamin D Receptor as a Prognostic Marker in Breast Cancer—A Cohort Study" Nutrients 16, no. 7: 931. https://doi.org/10.3390/nu16070931
APA StyleHuss, L., Gulz-Haake, I., Nilsson, E., Tryggvadottir, H., Nilsson, L., Nodin, B., Jirström, K., Isaksson, K., & Jernström, H. (2024). The Vitamin D Receptor as a Prognostic Marker in Breast Cancer—A Cohort Study. Nutrients, 16(7), 931. https://doi.org/10.3390/nu16070931